Showing posts with label Tibotec. Show all posts
Showing posts with label Tibotec. Show all posts
Tuesday, April 24, 2012
J&J open to partnering with Vertex in HCV drug development...
Posted on 4/20/12 on Bloomberg.com. The growing body of evidence in HCV drug development suggests that alliances are important (unless you happen to be Gilead) especially with partners that are owned by deep-pocketed, well diversified organizations like Johnson and Johnson. Hopefully J&J can put back some luster on Vertex's non-nuc VX-222. Actually, despite it's inherent relative lower barrier of resistance, it's a good drug - QD dosing, pretty powerful, clean and low potential for drug interactions. Just needs the right partners in a regimen. TMC435 may be one of 'em - QD dosing, powerful, no need for ritonavir and thus no ritonavir baggage - sounds good on paper, anyway.
J&J Open to Expanding Hepatitis C Cooperation With Vertex
By Makiko Kitamura - Apr 20, 2012 8:09 AM PT
Johnson & Johnson (JNJ)’s Janssen unit said it may explore widening cooperation on hepatitis C with Vertex Pharmaceuticals Inc. (VRTX) that may develop in tandem with a separate partnership with Medivir AB (MVIRB) on the disease.
“We remain open to see if we can expand our collaboration,” Gaston Picchio, vice president of Janssen’s global clinical virology and hepatitic disease area, said in an interview today in Barcelona, where he’s attending the European Association for the Study of the Liver annual meeting. “Vertex has announced plans for developing interferon-free therapies. We are partners, so that puts us in a better position to be a part of that,” should studies prove to be promising.
Vertex said on April 18 that it will start enrolling patients in a mid-stage study combining three medicines, excluding interferon, a core component of the current standard of care. Vertex and competitors including Gilead Sciences Inc. (GILD), Bristol-Myers Squibb Co. (BMY) and Abbott Laboratories (ABT) are racing to develop next-generation treatments for hepatitis C that exclude interferon because of flu-like side effects.
Vertex and J&J collaborated to develop telaprevir, marketed as Incivek by Vertex in North America and as Incivo by Janssen in other regions including Europe. The drug was approved by regulators last year as a treatment for hepatitis C in combination with interferon and ribavirin.
Medivir Project
J&J, which has its headquarters in New Brunswick, New Jersey, is also developing the protease inhibitor TMC435 with Huddinge, Sweden-based Medivir, which has said mid-stage trials of the drug in interferon-free combinations with Gilead’s 7977 and with Bristol-Myers’s daclatasvir experimental drugs are starting in the second quarter.
While J&J and Medivir are also developing the TMC647 polymerase inhibitor, Vertex’s VX-222 compound in the same class of drugs is further along in development. VX-222 is one of the three drugs included in Cambridge, Massachusetts-based Vertex’s mid-stage interferon-free treatment study.
Meanwhile, J&J is also “committed” to improving the labeling of Incivo by conducting further trials that examine less frequent dosage as well as efficacy in patients also infected by the HIV virus and those who have had liver transplants, Picchio said.
To contact the reporter on this story: Makiko Kitamura in Barcelona via mkitamura1@bloomberg.net
To contact the editor responsible for this story: Phil Serafino at pserafino@bloomberg.net
Saturday, January 14, 2012
Idenix seeks a partner for IDX184...
From Bloomberg News: Idenix CEO Ron Renaud announces they need a protease inhibitor or NS5A inhibitor-weilding partner for their HCV nuc, IDX184. Analysts speculate that Tibotec or Merck may be attractive partners.
Idenix Seeks Partner for Hepatitis C Combination Drug, CEO Renaud Says
By Sasha Damouni - Jan 13, 2012 1:05 PM PT .
...
Idenix Pharmaceuticals Inc. (IDIX), the developer of an experimental hepatitis C drug, is in talks to find a partner to create a combination treatment to fight the virus, Chief Executive Officer Ron Renaud said.
“If we think about how we can be very competitive, it is going to be about combining our compound with others,” Renaud said in an interview at the J.P. Morgan Healthcare Conference in San Francisco. That will be “our whole strategy.”
The Cambridge, Massachusetts-based biotechnology company finished the year with $118 million in cash, “enough to take us through to the end of this year,” Renaud said. There is a mid- year goal to find a partner for their drug, as part of a process of “evaluating paths forward,” he said.
The development of drug cocktails for HIV, the virus that causes AIDS, “is a very good road map for what could happen in hepatitis C,” Renaud said. HIV treatment involves a “combination of compounds with different mechanisms of action and compensating resistance profiles that beat the disease.”
Renaud declined to comment on whether the company may be acquired as the result of other recent purchases in the hepatitis C field.
Idenix gained 13 percent to $14.42 at the close in New York. The shares have more than doubled since Jan. 7 when Bristol-Myers Squibb Co. (BMY) said it would pay about $2.5 billion in cash for Inhibitex, a rival in a possible $20 billion hepatitis C market. Pharmasset, the maker of another experimental treatment for the virus, agreed on Nov. 21 to be acquired by Gilead Sciences Inc. (GILD) for $10.8 billion.
Safer Treatments
As many as 170 million people worldwide carry the hepatitis C virus, and current drugs, given through injection, can have side effects that make therapy difficult to endure. The new medicines are designed to be taken as pills, with a higher cure rate and fewer side effects.
On Jan. 9, Idenix reported that its lead drug candidate for hepatitis C, called IDX184, showed no serious side effects in patients after 28 days of treatment. Renaud said the company had submitted the data to the U.S. Food and Drug Administration, and expects to hear whether restrictions on its trials are lifted within a month.
“We are certainly going to combine IDX184 with protease inhibitors, and maybe a NS5A inhibitor,” Renaud said yesterday, describing drugs that attack different checkpoints for the disease as it moved through the human body.
While people are “very excited about the prospects” of an Idenix takeover, at current trading levels, the “valuation is very rich for M&A,” said Brian Skorney, an analyst at Brean Murray Carret & Co in New York.
Skorney said IDX184 needs another potent drug to “cover for its weaknesses” and pointed toward Merck & Co., the second- largest U.S. drugmaker, as an ideal suitor with its experimental protease inhibitor, MK-5172. He said Johnson & Johnson, the world’s biggest health-care products company, also may have an interest because of its hepatitis C research program.
To contact the reporter on this story: Sasha Damouni in New York at sdamouni2@bloomberg.net
To contact the editors responsible for this story: Reg Gale at rgale5@bloomberg.net; Brad Skillman at bskillman1@bloomberg.net
Idenix Seeks Partner for Hepatitis C Combination Drug, CEO Renaud Says
By Sasha Damouni - Jan 13, 2012 1:05 PM PT .
...
Idenix Pharmaceuticals Inc. (IDIX), the developer of an experimental hepatitis C drug, is in talks to find a partner to create a combination treatment to fight the virus, Chief Executive Officer Ron Renaud said.
“If we think about how we can be very competitive, it is going to be about combining our compound with others,” Renaud said in an interview at the J.P. Morgan Healthcare Conference in San Francisco. That will be “our whole strategy.”
The Cambridge, Massachusetts-based biotechnology company finished the year with $118 million in cash, “enough to take us through to the end of this year,” Renaud said. There is a mid- year goal to find a partner for their drug, as part of a process of “evaluating paths forward,” he said.
The development of drug cocktails for HIV, the virus that causes AIDS, “is a very good road map for what could happen in hepatitis C,” Renaud said. HIV treatment involves a “combination of compounds with different mechanisms of action and compensating resistance profiles that beat the disease.”
Renaud declined to comment on whether the company may be acquired as the result of other recent purchases in the hepatitis C field.
Idenix gained 13 percent to $14.42 at the close in New York. The shares have more than doubled since Jan. 7 when Bristol-Myers Squibb Co. (BMY) said it would pay about $2.5 billion in cash for Inhibitex, a rival in a possible $20 billion hepatitis C market. Pharmasset, the maker of another experimental treatment for the virus, agreed on Nov. 21 to be acquired by Gilead Sciences Inc. (GILD) for $10.8 billion.
Safer Treatments
As many as 170 million people worldwide carry the hepatitis C virus, and current drugs, given through injection, can have side effects that make therapy difficult to endure. The new medicines are designed to be taken as pills, with a higher cure rate and fewer side effects.
On Jan. 9, Idenix reported that its lead drug candidate for hepatitis C, called IDX184, showed no serious side effects in patients after 28 days of treatment. Renaud said the company had submitted the data to the U.S. Food and Drug Administration, and expects to hear whether restrictions on its trials are lifted within a month.
“We are certainly going to combine IDX184 with protease inhibitors, and maybe a NS5A inhibitor,” Renaud said yesterday, describing drugs that attack different checkpoints for the disease as it moved through the human body.
While people are “very excited about the prospects” of an Idenix takeover, at current trading levels, the “valuation is very rich for M&A,” said Brian Skorney, an analyst at Brean Murray Carret & Co in New York.
Skorney said IDX184 needs another potent drug to “cover for its weaknesses” and pointed toward Merck & Co., the second- largest U.S. drugmaker, as an ideal suitor with its experimental protease inhibitor, MK-5172. He said Johnson & Johnson, the world’s biggest health-care products company, also may have an interest because of its hepatitis C research program.
To contact the reporter on this story: Sasha Damouni in New York at sdamouni2@bloomberg.net
To contact the editors responsible for this story: Reg Gale at rgale5@bloomberg.net; Brad Skillman at bskillman1@bloomberg.net
Tuesday, December 6, 2011
Zacks Investment Research on HCV market....
Zacks analysis of the current HCV market and speculation of what's to come. Interesting read especially if you're new to the HCV drug development space.
Spotlight On Hepatitis-C Market
By Zacks Investment Research on December 6, 2011
Is the hepatitis-C market the next Mecca for the pharma/biotech sector? It seems so if we go by the flurry of activity and heightened interest in this market in the past few quarters. The hepatitis-C virus (HCV) market seems to have caught the eye of several pharma/biotech companies – as evident by the deals being signed for the development of drugs for the treatment of HCV.
We are talking about the recent announcements made by big players like Johnson & Johnson (NYSE:JNJ), Bristol-Myers Squibb (NYSE:BMY) and Gilead Sciences, Inc. (NASDAQ:GILD). All three companies have made it clear they want a piece of the HCV market pie.
Johnson & Johnson’s Tibotec Pharmaceuticals and Bristol-Myers Squibb recently announced that they have decided to join forces for the development of Bristol-Myers’ daclatasvir (BMS-790052) in combination with Tibotec’s TMC435, for the treatment of chronic HCV. What the partners are aiming to do is create an oral once-daily interferon-free cocktail treatment for HCV patients.
Bristol-Myers and Johnson & Johnson’s announcement comes on the heels of Gilead’s announcement regarding its intention to buy Pharmasset, Inc. (NASDAQ:VRUS), a company focused on developing HCV treatments. We think the main attraction for Gilead in this $11 billion deal is Pharmasset’s HCV pipeline. Lead candidate PSI-7977 is currently in two phase III studies, with a third phase III study scheduled to commence in the first half of 2012. Successful development could lead to US approval in 2014 thereby making Gilead a front-runner in the oral once-daily interferon-free cocktail treatment HCV market.
We note that both TMC435 and daclatasvir are being evaluated separately in combination with Pharmasset’s PSI-7977.
The Allure of the HCV Market
HCV is a hot development area which has come into the limelight with the launch of two new treatments – Vertex Pharmaceuticals’ (NASDAQ:VRTX) Incivek and Merck’s (NYSE:MRK) Victrelis. Both drugs gained approval in the US earlier this year. Incivek, which was launched in May 2011, posted a whopping $419.6 million in sales in the first full quarter of its launch.
So, with two new recently launched products in the market, why is the HCV market considered so attractive? Firstly, it is estimated that about 170 million people suffer from HCV infection across the world. However, the treated population is much lower. In major markets like the US, EU, Japan, Australia, Turkey, Canada, etc. only 200,000 HCV patients out of a total of more than 12 million are estimated to receive treatment each year. This means a huge number of HCV patients go untreated, leaving the field open for new treatments.
Secondly, the current standard of care comes with several side effects which make it difficult for patients to remain on treatment. A 48-week course of both peg-interferon (peg-INF – weekly injections) and ribavirin (RBV – oral drug), are the standard treatment for genotype 1 HCV infection. However, this treatment regimen is associated with significant side-effects like fatigue, flu-like symptoms, rash, depression and anemia.
With a large number of HCV patients failing to achieve a sustained viral response (SVR) on the current standard of care, there are several patients who would be open to treatment with new and potentially more effective therapies.
These factors have made the HCV market an attractive commercial opportunity for pharma and biotech companies. Victrelis and Incivek are examples of the changing treatment regimen in the HCV market. Both are protease inhibitors which when added to the standard of care reduce the treatment period and also improve the treatment outcome. However, both need to be administered with peg-IFN and RBV – this leaves the path open for the introduction of treatments with fewer side effects.
Cocktail Therapy – The Next Big Thing in HCV
Companies like Johnson & Johnson and Gilead are trying to develop the next crop of drugs, which are expected to change the treatment paradigm for HCV patients by providing them with all-oral treatment regimens. The aim is to develop a treatment which does not require the administration of interferon, thereby doing away with a whole range of side effects. The treatment duration will also be shorter.
Treatments being developed include HCV polymerase inhibitors and HCV NS5A inhibitors. The future HCV market will most likely consist of cocktail treatment regimens developed by combining different oral treatments.
Vertex Pharma has also recognized the need to continually evolve the HCV treatment pattern and is developing an all-oral combination of VX-222 (a polymerase inhibitor) and Incivek without peg-IFN.
Who Will Win the Rat Race?
With several companies pursuing cocktail therapies for HCV, it will be interesting to see which of these companies will be the first to hit the market with a new treatment option. Currently, it looks like Gilead might be the front-runner assuming the Pharmasset acquisition goes through.
Spotlight On Hepatitis-C Market
By Zacks Investment Research on December 6, 2011
Is the hepatitis-C market the next Mecca for the pharma/biotech sector? It seems so if we go by the flurry of activity and heightened interest in this market in the past few quarters. The hepatitis-C virus (HCV) market seems to have caught the eye of several pharma/biotech companies – as evident by the deals being signed for the development of drugs for the treatment of HCV.
We are talking about the recent announcements made by big players like Johnson & Johnson (NYSE:JNJ), Bristol-Myers Squibb (NYSE:BMY) and Gilead Sciences, Inc. (NASDAQ:GILD). All three companies have made it clear they want a piece of the HCV market pie.
Johnson & Johnson’s Tibotec Pharmaceuticals and Bristol-Myers Squibb recently announced that they have decided to join forces for the development of Bristol-Myers’ daclatasvir (BMS-790052) in combination with Tibotec’s TMC435, for the treatment of chronic HCV. What the partners are aiming to do is create an oral once-daily interferon-free cocktail treatment for HCV patients.
Bristol-Myers and Johnson & Johnson’s announcement comes on the heels of Gilead’s announcement regarding its intention to buy Pharmasset, Inc. (NASDAQ:VRUS), a company focused on developing HCV treatments. We think the main attraction for Gilead in this $11 billion deal is Pharmasset’s HCV pipeline. Lead candidate PSI-7977 is currently in two phase III studies, with a third phase III study scheduled to commence in the first half of 2012. Successful development could lead to US approval in 2014 thereby making Gilead a front-runner in the oral once-daily interferon-free cocktail treatment HCV market.
We note that both TMC435 and daclatasvir are being evaluated separately in combination with Pharmasset’s PSI-7977.
The Allure of the HCV Market
HCV is a hot development area which has come into the limelight with the launch of two new treatments – Vertex Pharmaceuticals’ (NASDAQ:VRTX) Incivek and Merck’s (NYSE:MRK) Victrelis. Both drugs gained approval in the US earlier this year. Incivek, which was launched in May 2011, posted a whopping $419.6 million in sales in the first full quarter of its launch.
So, with two new recently launched products in the market, why is the HCV market considered so attractive? Firstly, it is estimated that about 170 million people suffer from HCV infection across the world. However, the treated population is much lower. In major markets like the US, EU, Japan, Australia, Turkey, Canada, etc. only 200,000 HCV patients out of a total of more than 12 million are estimated to receive treatment each year. This means a huge number of HCV patients go untreated, leaving the field open for new treatments.
Secondly, the current standard of care comes with several side effects which make it difficult for patients to remain on treatment. A 48-week course of both peg-interferon (peg-INF – weekly injections) and ribavirin (RBV – oral drug), are the standard treatment for genotype 1 HCV infection. However, this treatment regimen is associated with significant side-effects like fatigue, flu-like symptoms, rash, depression and anemia.
With a large number of HCV patients failing to achieve a sustained viral response (SVR) on the current standard of care, there are several patients who would be open to treatment with new and potentially more effective therapies.
These factors have made the HCV market an attractive commercial opportunity for pharma and biotech companies. Victrelis and Incivek are examples of the changing treatment regimen in the HCV market. Both are protease inhibitors which when added to the standard of care reduce the treatment period and also improve the treatment outcome. However, both need to be administered with peg-IFN and RBV – this leaves the path open for the introduction of treatments with fewer side effects.
Cocktail Therapy – The Next Big Thing in HCV
Companies like Johnson & Johnson and Gilead are trying to develop the next crop of drugs, which are expected to change the treatment paradigm for HCV patients by providing them with all-oral treatment regimens. The aim is to develop a treatment which does not require the administration of interferon, thereby doing away with a whole range of side effects. The treatment duration will also be shorter.
Treatments being developed include HCV polymerase inhibitors and HCV NS5A inhibitors. The future HCV market will most likely consist of cocktail treatment regimens developed by combining different oral treatments.
Vertex Pharma has also recognized the need to continually evolve the HCV treatment pattern and is developing an all-oral combination of VX-222 (a polymerase inhibitor) and Incivek without peg-IFN.
Who Will Win the Rat Race?
With several companies pursuing cocktail therapies for HCV, it will be interesting to see which of these companies will be the first to hit the market with a new treatment option. Currently, it looks like Gilead might be the front-runner assuming the Pharmasset acquisition goes through.
Tuesday, November 15, 2011
Medivir updates investors on Hepatitis C programs...
Medivir offers an update on it's HCV development projects including the phase IIb trials for it's once daily. HCV protease inhibitor TMC435 and the early development programs for it's HCV nucleoside and a nucleotide inhibitors. For TMC435: results from the PILLAR trial looking at TMC435 + P/R in treatment naive genotype 1 subjects found 81-86% of patients achieved SVR24, compared to 65% in the placebo + P/R arm. A majority of patients (86%) in the TMC435 treatment arms had a shortened treatment duration of treatment (24 weeks), compared to a 48 weeks in the placebo + P/R arm. For the ASPIRE trial, looking at TMC435 + P/R in partial and null responders to previous treatment. The TMC435 subgroups achieved substantially higher viral cure rates (SVR24) compared to the control group (PegIFN and RBV alone): 85% vs. 37% in prior relapsers, 75% vs. 9% in prior partial responders and 51% vs. 19% in prior null responders. Other interesting notes include a change in primary endpoint from SVR24 to SVR12 in the TMC435 Phase III trials; a Phase III TMC435 + P/R vs Telaprevir + P/R in nonresponders yet to be started; an interferon-free, combination trial looking at TMC435 + Pharmasset's PSI-7977 with and without ribavirin in genotype 1 non-responders. We're likely to see more companies pair combinations of drugs as the 2nd and 3rd generation DAAs move forward in development and others are abandoned due to inferior efficacy and/or side effect issues.
Medivir: Key News from the Ongoing Capital Markets Day
HUDDINGE, Sweden, Nov 15, 2011 (BUSINESS WIRE) -- Regulatory News:
Medivir AB, a research-based speciality pharmaceutical company focused on infectious diseases, reports the following key news concerning their hepatitis C projects.
Medivir programmes in collaboration with Tibotec Pharmaceuticals Medivir and Tibotec Pharmaceuticals have two programmes for the development of antiviral therapies for future treatment of hepatitis C (HCV), these are based on the HCV protease and polymerase drug targets.
In the protease project, TMC435 is in global phase III development in both treatment naive and in patients that have relapsed after previous treatment with pegylated interferon (PegIFN) and ribavirin (RBV) in patients with chronic hepatitis C genotype 1.
The HCV polymerase collaboration program consists of two early development projects, a nucleoside and a nucleotide inhibitor.
TMC435 (NS3/4A protease inhibitor) presently in development in Hepatitis C genotype 1 infected patients.
Phase IIb studies Final SVR24 data from the phase IIb study PILLAR, in treatment-naive patients, was presented last week at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco, CA, USA. Results from this final PILLAR analysis showed that TMC435 administered in combination with peginterferon a-2a and ribavirin (PR) resulted in significantly higher sustained virologic response (SVR) rates compared to placebo plus PR, with the majority of TMC435 patients able to shorten total treatment duration to 24 weeks based on response-guided therapy.
-- In the 150 mg TMC435 treatment groups, 81-86 percent of patients achieved SVR24, compared to 65 percent of patients treated in the placebo arm. In addition, 86 percent of patients in the TMC435 treatment arms had a shortened treatment duration of 24 weeks, compared to a 48 weeks treatment duration for patients who received placebo plus P/R.
-- The once daily dosed TMC435 was generally safe and well tolerated at all doses and treatment durations.
Medivir recently issued a press release on final results from phase IIb study ASPIRE This trial evaluated TMC435 once daily in addition to pegylated interferon (PegIFN) and ribavirin (RBV) in patients with chronic hepatitis C whose prior treatment with PegIFN and RBV was unsuccessful either because they relapsed, had a partial response or had a null response.
-- Data from the ASPIRE study showed that patients in each of these subgroups who were treated with TMC435-based combination therapy achieved superior rates of sustained virologic response (viral cure) compared to those retreated with pegylated-interferon and ribavirin alone.
-- All TMC435 subgroups achieved substantially higher viral cure rates (SVR24) compared to control group (PegIFN and RBV alone): 85% vs. 37% in prior relapsers, 75% vs. 9% in prior partial responders and 51% vs. 19% in prior null responders.
-- The once daily TMC435 was generally safe and well tolerated at all doses and treatment durations. Phase III studies
SVR12 - new endpoint
-- In the ongoing phase III studies in naive and patients that have relapsed following previous treatment, the primary endpoint has been changed from SVR24 to SVR12 following recent discussions with the FDA. These studies (QUEST 1 &2 and PROMISE) were all fully recruited in August.
Phase III study in non-responder patients to be initiated
-- Phase III study in prior partial and null responder HCV genotype 1 patients will start within six months. This study will evaluate efficacy, safety and tolerability for TMC435 vs telaprevir in combination with PegINFa-2a and Ribavirin in chronic Hepatitis C patients.
Phase II interferon free combination study with TMC435 and PSI-7977
-- This interferon free phase II combination study will commence shortly. It will evaluate TMC435 and PSI-7977 in combination with and without ribavirin for 12 and 24 weeks in genotype 1 patients who had a prior null response to Peg-IFN/RBV. The study design is now posted on www.clinicaltrials.gov .
HCV polymerase collaboration
TMC649128 TMC649128, the first NS5B nucleoside polymerase inhibitor under the collaboration, entered into clinical development in Q1-2011. It was safe and well tolerated at all doses tested for up to 14 days. However the antiviral activity failed to meet the target product profile and therefore the clinical development has now been discontinued.
Nucleotide program The focus of HCV polymerase collaboration is now on a liver targeted nucleotide polymerase inhibitor program. A clinical candidate has been selected and the project is now in preclinical development stage.
Capital Markets Day Presentation The presentation from this research & development update is available on our website under the heading Investor Relations / Latest Events.
For more information about Medivir, please visit the Company's website: www.medivir.com .
This information was brought to you by Cision http://www.cisionwire.com
SOURCE: Medivir
Medivir: Key News from the Ongoing Capital Markets Day
HUDDINGE, Sweden, Nov 15, 2011 (BUSINESS WIRE) -- Regulatory News:
Medivir AB, a research-based speciality pharmaceutical company focused on infectious diseases, reports the following key news concerning their hepatitis C projects.
Medivir programmes in collaboration with Tibotec Pharmaceuticals Medivir and Tibotec Pharmaceuticals have two programmes for the development of antiviral therapies for future treatment of hepatitis C (HCV), these are based on the HCV protease and polymerase drug targets.
In the protease project, TMC435 is in global phase III development in both treatment naive and in patients that have relapsed after previous treatment with pegylated interferon (PegIFN) and ribavirin (RBV) in patients with chronic hepatitis C genotype 1.
The HCV polymerase collaboration program consists of two early development projects, a nucleoside and a nucleotide inhibitor.
TMC435 (NS3/4A protease inhibitor) presently in development in Hepatitis C genotype 1 infected patients.
Phase IIb studies Final SVR24 data from the phase IIb study PILLAR, in treatment-naive patients, was presented last week at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco, CA, USA. Results from this final PILLAR analysis showed that TMC435 administered in combination with peginterferon a-2a and ribavirin (PR) resulted in significantly higher sustained virologic response (SVR) rates compared to placebo plus PR, with the majority of TMC435 patients able to shorten total treatment duration to 24 weeks based on response-guided therapy.
-- In the 150 mg TMC435 treatment groups, 81-86 percent of patients achieved SVR24, compared to 65 percent of patients treated in the placebo arm. In addition, 86 percent of patients in the TMC435 treatment arms had a shortened treatment duration of 24 weeks, compared to a 48 weeks treatment duration for patients who received placebo plus P/R.
-- The once daily dosed TMC435 was generally safe and well tolerated at all doses and treatment durations.
Medivir recently issued a press release on final results from phase IIb study ASPIRE This trial evaluated TMC435 once daily in addition to pegylated interferon (PegIFN) and ribavirin (RBV) in patients with chronic hepatitis C whose prior treatment with PegIFN and RBV was unsuccessful either because they relapsed, had a partial response or had a null response.
-- Data from the ASPIRE study showed that patients in each of these subgroups who were treated with TMC435-based combination therapy achieved superior rates of sustained virologic response (viral cure) compared to those retreated with pegylated-interferon and ribavirin alone.
-- All TMC435 subgroups achieved substantially higher viral cure rates (SVR24) compared to control group (PegIFN and RBV alone): 85% vs. 37% in prior relapsers, 75% vs. 9% in prior partial responders and 51% vs. 19% in prior null responders.
-- The once daily TMC435 was generally safe and well tolerated at all doses and treatment durations. Phase III studies
SVR12 - new endpoint
-- In the ongoing phase III studies in naive and patients that have relapsed following previous treatment, the primary endpoint has been changed from SVR24 to SVR12 following recent discussions with the FDA. These studies (QUEST 1 &2 and PROMISE) were all fully recruited in August.
Phase III study in non-responder patients to be initiated
-- Phase III study in prior partial and null responder HCV genotype 1 patients will start within six months. This study will evaluate efficacy, safety and tolerability for TMC435 vs telaprevir in combination with PegINFa-2a and Ribavirin in chronic Hepatitis C patients.
Phase II interferon free combination study with TMC435 and PSI-7977
-- This interferon free phase II combination study will commence shortly. It will evaluate TMC435 and PSI-7977 in combination with and without ribavirin for 12 and 24 weeks in genotype 1 patients who had a prior null response to Peg-IFN/RBV. The study design is now posted on www.clinicaltrials.gov .
HCV polymerase collaboration
TMC649128 TMC649128, the first NS5B nucleoside polymerase inhibitor under the collaboration, entered into clinical development in Q1-2011. It was safe and well tolerated at all doses tested for up to 14 days. However the antiviral activity failed to meet the target product profile and therefore the clinical development has now been discontinued.
Nucleotide program The focus of HCV polymerase collaboration is now on a liver targeted nucleotide polymerase inhibitor program. A clinical candidate has been selected and the project is now in preclinical development stage.
Capital Markets Day Presentation The presentation from this research & development update is available on our website under the heading Investor Relations / Latest Events.
For more information about Medivir, please visit the Company's website: www.medivir.com .
This information was brought to you by Cision http://www.cisionwire.com
SOURCE: Medivir
Thursday, September 1, 2011
TMC435 Phase III Trials for genotype-1 HCV patients completely enrolled...
(Medivir/Tibotec clinical trials for their HCV protease inhibitor TMC435(QUEST 1 and QUEST 2 for genotype 1 tx-naive patients and PROMISE for tx-experienced relapsers) are fully enrolled. Good news for everybody. The companies continue to build anticipation for the start and eventual interim data looking Medivir/Tibotec/Pharmasset's proof-of-concept oral, interferon-free phase 2 trial, looking at a TMC435 and PSI-7977 combo. An all-oral, once-daily regimen would be a tremendous accomplishment.)
Medivir: Completed Enrollment of Three Global Phase 3 Trials for TMC435 in Chronic Hepatitis C Genotype-1 Infected Patients
HUDDINGE, Sweden, Aug 31, 2011 (BUSINESS WIRE) -- Regulatory News:
MedivirAB (omx:MVIR) is an emerging research-based specialty pharmaceutical company focused on infectious diseases.
Medivir today announced that its investigational protease inhibitor TMC435, developed by Tibotec Pharmaceuticals, has successfully completed enrollment of three ongoing global phase 3 trials and further reports that all patients are now on TMC435 or active control treatment. The trials are QUEST 1 and QUEST 2, in treatment naive patients, and PROMISE in the treatment experienced relapser patient population. In all three trials, the duration of total treatment is response guided and patients in the TMC435 arms are eligible to stop all treatment at week 24 if predefined response-guided criteria are met.
Medivir recently announced that TMC435 had received "Fast Track" designation by the U.S. Food and Drug Administration ("FDA") for the treatment of chronic hepatitis C (CHC) genotype-1 infection. This is based on TMC435's potential to address unmet medical needs in the treatment of chronic HCV infection.
In parallel to these trials, phase 3 studies for TMC435 in Japan, in both treatment naive and treatment experienced hepatitis C genotype-1 infected patients, have also completed enrollment.
Global Phase 3 Program in brief:
- TMC435-C208 or QUEST-1 includes approximately 375 treatment-naive patients
- TMC435-C216 or QUEST-2 includes approximately 375 treatment-naive patients
- TMC435-C3007 or PROMISE includes approximately 375 who have relapsed after prior interferon-based treatment
Bertil Samuelsson, Chief Scientific Advisor at Medivir, comments - "We are extremely excited to have completed the enrollment and patient dosing in three large global phase 3 trials. It is a monumental milestone step for Medivir as a company and for TMC435 progress towards market registration. The completed enrollment of phase 3 studies for TMC435 in Japan represents another key project milestone achievement."
About TMC435
TMC435, an investigational CHC protease inhibitor currently in phase 3 clinical development, is a highly potent, selective and safe once-daily (q.d.) drug jointly developed by Tibotec Pharmaceuticals to treat chronic hepatitis C virus infections.
TMC435 is being developed both in combination with PegIFN/RBV and in combination with Direct-acting Antiviral (DAA) agents without peginterferon and with or without ribavirin (RBV).
In June 2011 the combination study of TMC435 with TMC647055, a non-nucleoside NS5B polymerase inhibitor being developed by Tibotec Pharmaceuticals, was initiated and in July 2011 Medivir confirmed the intention to start a proof-of-concept oral, interferon-free phase 2 trial, investigating the combination of TMC435 and Pharmasset's PSI-7977, a once daily nucleotide NS5B polymerase inhibitor. Phase 3 programs for TMC435 are also ongoing in Japan.
In parallel with the recent start of the global phase 3-studies, TMC435 is currently in a follow up phase in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naive and in G1 patients that failed previous IFN-based treatment. More safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2011.
For additional information from these studies, please see www.medivir.com and www.clinicaltrials.gov
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.
About Medivir
Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company's key pipeline asset is TMC435, a novel protease inhibitor is in phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals.
In June 2011, Medivir acquired the specialty pharmaceutical company BioPhausia to ensure timely commercialization of TMC435 in the Nordic markets, once approved.
Medivir's first product, the unique cold sore product Xerese(R)/Xerclear(R) was launched on the US market in February 2011. Xerese(R)/Xerclear(R), which has been approved in both the US and Europe is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia. Rights in North America, Canada and Mexico have recently been sold to Meda AB. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.
For more information about Medivir, please visit the Company's website: www.medivir.com
This information was brought to you by Cision http://www.cisionwire.com
SOURCE: Medivir
Medivir: Completed Enrollment of Three Global Phase 3 Trials for TMC435 in Chronic Hepatitis C Genotype-1 Infected Patients
HUDDINGE, Sweden, Aug 31, 2011 (BUSINESS WIRE) -- Regulatory News:
MedivirAB (omx:MVIR) is an emerging research-based specialty pharmaceutical company focused on infectious diseases.
Medivir today announced that its investigational protease inhibitor TMC435, developed by Tibotec Pharmaceuticals, has successfully completed enrollment of three ongoing global phase 3 trials and further reports that all patients are now on TMC435 or active control treatment. The trials are QUEST 1 and QUEST 2, in treatment naive patients, and PROMISE in the treatment experienced relapser patient population. In all three trials, the duration of total treatment is response guided and patients in the TMC435 arms are eligible to stop all treatment at week 24 if predefined response-guided criteria are met.
Medivir recently announced that TMC435 had received "Fast Track" designation by the U.S. Food and Drug Administration ("FDA") for the treatment of chronic hepatitis C (CHC) genotype-1 infection. This is based on TMC435's potential to address unmet medical needs in the treatment of chronic HCV infection.
In parallel to these trials, phase 3 studies for TMC435 in Japan, in both treatment naive and treatment experienced hepatitis C genotype-1 infected patients, have also completed enrollment.
Global Phase 3 Program in brief:
- TMC435-C208 or QUEST-1 includes approximately 375 treatment-naive patients
- TMC435-C216 or QUEST-2 includes approximately 375 treatment-naive patients
- TMC435-C3007 or PROMISE includes approximately 375 who have relapsed after prior interferon-based treatment
Bertil Samuelsson, Chief Scientific Advisor at Medivir, comments - "We are extremely excited to have completed the enrollment and patient dosing in three large global phase 3 trials. It is a monumental milestone step for Medivir as a company and for TMC435 progress towards market registration. The completed enrollment of phase 3 studies for TMC435 in Japan represents another key project milestone achievement."
About TMC435
TMC435, an investigational CHC protease inhibitor currently in phase 3 clinical development, is a highly potent, selective and safe once-daily (q.d.) drug jointly developed by Tibotec Pharmaceuticals to treat chronic hepatitis C virus infections.
TMC435 is being developed both in combination with PegIFN/RBV and in combination with Direct-acting Antiviral (DAA) agents without peginterferon and with or without ribavirin (RBV).
In June 2011 the combination study of TMC435 with TMC647055, a non-nucleoside NS5B polymerase inhibitor being developed by Tibotec Pharmaceuticals, was initiated and in July 2011 Medivir confirmed the intention to start a proof-of-concept oral, interferon-free phase 2 trial, investigating the combination of TMC435 and Pharmasset's PSI-7977, a once daily nucleotide NS5B polymerase inhibitor. Phase 3 programs for TMC435 are also ongoing in Japan.
In parallel with the recent start of the global phase 3-studies, TMC435 is currently in a follow up phase in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naive and in G1 patients that failed previous IFN-based treatment. More safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2011.
For additional information from these studies, please see www.medivir.com and www.clinicaltrials.gov
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.
About Medivir
Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company's key pipeline asset is TMC435, a novel protease inhibitor is in phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals.
In June 2011, Medivir acquired the specialty pharmaceutical company BioPhausia to ensure timely commercialization of TMC435 in the Nordic markets, once approved.
Medivir's first product, the unique cold sore product Xerese(R)/Xerclear(R) was launched on the US market in February 2011. Xerese(R)/Xerclear(R), which has been approved in both the US and Europe is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia. Rights in North America, Canada and Mexico have recently been sold to Meda AB. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.
For more information about Medivir, please visit the Company's website: www.medivir.com
This information was brought to you by Cision http://www.cisionwire.com
SOURCE: Medivir
Thursday, August 11, 2011
FDA approves Gilead's once-daily HIV pill, Complera
(The FDA approves Complera - a once daily combination of Truvada and Edurant - for the treatment of HIV in treatment naive subjects. New drug combinations that allow for less pill burden are always welcome and help increase adherence. However when it comes to HIV, providers are always looking for options down the line if the patient happens to become resistant to therapy. Two things to take note of in the press release:
1. "The observed virologic failure rate in rilpivirine-treated subjects conferred a higher rate of overall treatment resistance and cross-resistance to the NNRTI class compared to efavirenz."
2. "More subjects treated with rilpivirine developed lamivudine/emtricitabine associated resistance compared to efavirenz."
This essentially means that a patient becoming resistant to either the Truvada or Edurant portion of the regimen would potentially have less options for sequential therapy down the line compared to the efavirenz-containing regimen used in the control arm of the Complera studies.
The rilpivirine-portion of the drug also appears to be heavily effected by gastric PH and potential for drug-drug interactions involving CYP3A which may lower rilpivirine to sub-therapeutic levels and potentially be a mechanism of resistance )
U.S. Food and Drug Administration Approves Gilead Sciences’ Complera™, a New Complete Once-Daily, Single-Tablet Regimen for HIV-1 Infection in Treatment-Naïve Adults
- Complera Combines the Most-Prescribed HIV Product in the United States with the Newest Antiretroviral Agent Approved by the FDA -
- Approval Marks Gilead's Second Successful Collaboration to Develop a Complete Single-Tablet Regimen for HIV/AIDS -
FOSTER CITY, Calif., Aug 10, 2011 (BUSINESS WIRE) --
Gilead Sciences, Inc. (Nasdaq:GILD) today announced that the U.S. Food and Drug Administration (FDA) has approved Complera(TM) (emtricitabine/rilpivirine/tenofovir disoproxil fumarate), a complete single-tablet regimen for the treatment of HIV-1 infection in treatment-naïve adults. Complera combines three antiretroviral medications in one daily tablet - Gilead's Truvada(R), which is a fixed-dose combination of the two nucleoside reverse transcriptase inhibitors emtricitabine and tenofovir disoproxil fumarate, and Tibotec Pharmaceuticals' non-nucleoside reverse transcriptase inhibitor, rilpivirine (marketed as Edurant(TM) in the United States by Janssen Therapeutics, Division of Janssen Products, LP). Truvada and rilpivirine were approved by the FDA in August 2004 and May 2011, respectively, for use as part of HIV combination therapy.
"In the 30 years since the first AIDS cases were reported, we've made incredible strides in the treatment of this disease," said Tony Mills, MD, Director of Medical Research, Anthony Mills MD, Inc. and a participating investigator in ongoing Complera studies. "The concept of a single-tablet regimen has become a goal in HIV drug development, and the standard of care in medical practice in the United States. However, no one therapy is appropriate for all patients. Given its efficacy, safety and convenience, the availability of Complera represents an exciting milestone in addressing the individual needs of patients new to HIV therapy."
The approval of Complera is supported by 48-week data from two Phase 3 double-blind, active controlled, randomized studies (ECHO and THRIVE) conducted by Tibotec that evaluated the safety and efficacy of rilpivirine compared to efavirenz among treatment-naïve HIV-1 infected adults. Both arms of the study were administered with a background regimen, in which the majority of patients in the rilpivirine arm received Truvada. A bioequivalence study, conducted by Gilead, demonstrated that the co-formulated single-tablet regimen achieved the same levels of medication in the blood as emtricitabine plus rilpivirine plus tenofovir disoproxil fumarate.
"Complera is the second complete single-tablet regimen that Gilead has introduced, and it represents a collaboration between two organizations that share a vision of simplifying HIV therapy for patients," said John C. Martin, PhD, Chairman and Chief Executive Officer, Gilead Sciences. "Tremendous progress has been made in the field of HIV, but we recognize new therapies are still needed, and we continue to work to advance options that address the needs of patients."
Complera is the second complete antiretroviral treatment regimen for HIV-1 available to treatment-naïve patients in a single once-daily pill. The first, Atripla(R) (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg), is marketed by Gilead and Bristol-Myers Squibb. Complera does not cure HIV-1 infection or help prevent the transmission of HIV to others. Complera has Boxed Warnings including lactic acidosis/severe hepatomegaly with steatosis and post treatment acute exacerbation of hepatitis B; see below for additional important safety information. The following points should be considered when initiating therapy with Complera:
More rilpivirine-treated subjects with HIV-1 RNA greater than 100,000 copies/mL at the start of therapy experienced virologic failure compared to subjects with HIV-1 RNA less than 100,000 copies/mL at the start of therapy.
The observed virologic failure rate in rilpivirine-treated subjects conferred a higher rate of overall treatment resistance and cross-resistance to the NNRTI class compared to efavirenz.
More subjects treated with rilpivirine developed lamivudine/emtricitabine associated resistance compared to efavirenz.
Complera is not recommended for patients less than 18 years of age.
Gilead first entered into a license and collaboration agreement with Tibotec for the development and commercialization of Complera in July 2009. Under the terms of the agreement, Gilead will assume the lead role in the manufacturing, registration, distribution and commercialization of Complera in the United States, Canada, Brazil, the European Union, Australia and New Zealand. Tibotec will be responsible for the commercialization of rilpivirine as a stand-alone product and will hold rights to co-detail Complera in these territories. A marketing application for the emtricitabine/rilpivirine/tenofovir disoproxil fumarate single-tablet regimen is currently pending in the European Union.
The companies also have finalized an agreement for the development and commercialization of the single-tablet regimen for the rest of world, including the developing world. Gilead will be responsible for the registration, distribution and commercialization of the single-tablet regimen in certain European countries, Latin America and the Caribbean. Tibotec will be responsible for all countries outside of the Gilead territories, the most significant of which include Asia Pacific, including Japan, the Middle East, Eastern Europe and all of Africa.
Important Product Safety Information About Complera, Including Boxed Warnings
BOXED WARNINGS: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including tenofovir disoproxil fumarate, a component of Complera, in combination with other antiretrovirals.
Complera is not approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of Complera have not been established in patients coinfected with HBV and HIV-1.Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued Emtriva or Viread, which are components of Complera.Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue Complera.If appropriate, initiation of anti-hepatitis B therapy may be warranted.
CONTRAINDICATIONS
Complera should not be co-administered with the following drugs, as significant decreases in rilpivirine plasma concentrations may occur due to CYP3A enzyme induction or gastric pH increase, which may result in loss of virologic response and possible resistance to Complera or to the class of NNRTIs:
the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin
the antimycobacterials rifabutin, rifampin, rifapentine
proton pump inhibitors, such as esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole
the glucocorticoid systemic dexamethasone (more than a single dose)
St John's wort (Hypericum perforatum)
WARNINGS AND PRECAUTIONS
New onset or worsening renal impairment
Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of tenofovir disoproxil fumarate. Assess creatinine clearance (CrCl) before initiating treatment with Complera. Monitor CrCl and serum phosphorus in patients at risk for renal impairment, including patients who have previously experienced renal events while receiving Hepsera(R) (adefovir dipivoxil). Avoid administering Complera with concurrent or recent use of nephrotoxic drugs. Patients with CrCl below 50 mL per minute should not receive Complera.
Drug Interactions
Complera should be used with caution when given with drugs that may reduce the exposure of rilpivirine.
Complera should be used with caution when co-administered with a drug with a known risk of Torsade de Pointes.
Depressive Disorders
The adverse reaction depressive disorders (depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, suicidal ideation) has been reported with rilpivirine. During the Phase 3 trials (N = 1,368), the incidence of depressive disorders (regardless of causality, severity) reported among rilpivirine (N = 686) or efavirenz (N = 682) was 8% and 6%, respectively. Most events were mild or moderate in severity. The incidence of Grade 3 and 4 depressive disorders (regardless of causality) was 1% for both rilpivirine and efavirenz. The incidence of discontinuation due to depressive disorders among rilpivirine or efavirenz was 1% in each arm. Suicide attempt was reported in 2 subjects in the rilpivirine arm while suicide ideation was reported in 1 subject in the rilpivirine arm and in 3 subjects in the efavirenz arm. Patients with severe depressive symptoms should seek immediate medical evaluation to assess the possibility that the symptoms are related to Complera, and if so, to determine whether the risks of continued therapy outweigh the benefits.
Decreases in bone mineral density
Bone mineral density (BMD) monitoring should be considered for patients who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Cases of osteomalacia (associated with proximal renal tubulopathy and which may contribute to fractures) have been reported in association with the use of tenofovir disoproxil fumarate.
Co-administration with other products
Complera should not be administered concurrently with other medicinal products containing any of the same active components, emtricitabine, rilpivirine, or tenofovir disoproxil fumarate (Emtriva, Edurant, Viread, Truvada, Atripla), with medicinal products containing lamivudine (Epivir, Epivir-HBV, Epzicom, Combivir, Trizivir), or with adefovir dipivoxil (Hepsera).
Fat redistribution
Redistribution/accumulation of body fat has been observed in patients receiving antiretroviral therapy.
Immune reconstitution syndrome
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including the components of Complera. Further evaluation and treatment may be necessary.
ADVERSE REACTIONS
The most common adverse drug reactions to rilpivirine (incidence greater than or equal to 2%, Grades 2-4) were insomnia and headache.
The most common adverse drug reactions to emtricitabine and tenofovir disoproxil fumarate (incidence greater-than or equal to 10%) were diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash.
DRUG INTERACTIONS
Complera should not be used with drugs where significant decreases in rilpivirine plasma concentrations may occur (See CONTRAINDICATIONS).
Complera is a complete regimen for the treatment of HIV-1 infection; therefore Complera should not be administered with other antiretroviral medications for the treatment of HIV-1 infection.
Drugs inducing or inhibiting CYP3A enzymes: Rilpivirine is primarily metabolized by cytochrome P450 (CYP) 3A, and drugs that induce or inhibit CYP3A may thus affect the clearance of rilpivirine. Coadministration of rilpivirine and drugs that induce CYP3A may result in decreased plasma concentrations of rilpivirine and loss of virologic response and possible resistance to rilpivirine or to the class of NNRTIs. Coadministration of rilpivirine and drugs that inhibit CYP3A may result in increased plasma concentrations of rilpivirine.
Drugs increasing gastric PH: Coadministration of rilpivirine with drugs that increase gastric pH may decrease plasma concentrations of rilpivirine and loss of virologic response and possible resistance to rilpivirine or to the class of NNRTIs.
Drugs affecting renal function: Since emtricitabine and tenofovir are primarily eliminated by the kidneys, coadministration of Complera with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of emtricitabine, tenofovir, and/or other renally eliminated drugs. Some examples include, but are not limited to, acyclovir, adefovir dipivoxil, cidofovir, ganciclovir, valacyclovir and valganciclovir.
QT prolonging drugs: There is limited information available on the potential for a pharmacodynamic interaction between rilpivirine and drugs that prolong the QTc interval of the electrocardiogram. In a study of healthy subjects, supratherapeutic doses of rilpivirine (75 mg once daily and 300 mg once daily) have been shown to prolong the QTc interval of the electrocardiogram. Complera should be used with caution when coadministered with a drug with a known risk of Torsade de Pointes.
DOSAGE AND ADMINISTRATION
Adults: The recommended dose of Complera is one tablet taken orally once daily with a meal.
Renal Impairment: Because Complera is a fixed-dose combination, it should not be prescribed for patients requiring dose adjustment such as those with moderate or severe renal impairment (creatinine clearance below 50 mL per minute).
Important Safety Product Information About Truvada, Including Boxed Warnings
Truvada, a combination of Emtriva (emtricitabine) and Viread (tenofovir disoproxil fumarate [DF]), is indicated in combination with other antiretroviral agents (such as non nucleoside reverse transcriptase inhibitors or protease inhibitors) for the treatment of HIV-1 infection.
The following points should be considered when initiating therapy with Truvada for the treatment of HIV-1 infection:
It is not recommended that Truvada be used as a component of a triple nucleoside regimen.
Truvada should not be coadministered with Atripla (efavirenz/emtricitabine/tenofovir DF), Emtriva, Viread, or lamivudine-containing products.
In treatment-experienced patients, the use of Truvada should be guided by laboratory testing and treatment history.
WARNINGS: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including Viread, a component of Truvada, in combination with other antiretrovirals.
Truvada is not approved for the treatment of chronic hepatitis B virus (HBV) infection, and the safety and efficacy of Truvada have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued Truvada. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue Truvada. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
WARNINGS AND PRECAUTIONS
New Onset or Worsening Renal Impairment
Emtricitabine and tenofovir are principally eliminated by the kidney. Renal impairment, including acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of tenofovir DF.
Assess CrCl before initiating treatment with Truvada. Routinely monitor CrCl and serum phosphorus in patients at risk for renal impairment, including patients who have previously experienced renal events while receiving Hepsera (adefovir dipivoxil).
Dosing interval adjustment of Truvada and close monitoring of renal function are recommended in all patients with CrCl 30-49 mL/min. No safety or efficacy data are available in patients with renal impairment who received Truvada using these dosing guidelines, so the potential benefit of Truvada therapy should be assessed against the potential risk of renal toxicity. Truvada should not be administered in patients with CrCl <30 mL/min or patients requiring hemodialysis. Avoid administering Truvada with concurrent or recent use of nephrotoxic drugs. Coadministration With Other Products Since Truvada contains emtricitabine and tenofovir DF, Truvada should not be coadministered with Atripla, Emtriva or Viread. Due to similarities between emtricitabine and lamivudine, Truvada should not be coadministered with other drugs containing lamivudine, including Combivir (zidovudine/lamivudine) Epivir or Epivir-HBV (lamivudine), Epzicom (abacavir sulfate/lamivudine), or Trizivir (abacavir sulfate/lamivudine/zidovudine). Truvada should not be administered with Hepsera. Bone Mineral Density Decreases in bone mineral density (BMD): BMD monitoring should be considered for HIV-1 infected patients who have a history of pathologic bone fracture or who are at risk for osteopenia. Cases of osteomalacia (associated with proximal renal tubulopathy and which may contribute to fractures) have been reported in association with the use of Viread. Fat Redistribution Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established. Immune Reconstitution Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including Truvada, which may necessitate further evaluation and treatment. Early Virologic Failure Triple nucleoside-only regimens: Early virologic failure has been reported in HIV-infected patients on regimens containing only 3 nucleoside reverse transcriptase inhibitors (NRTIs). Monitor carefully and consider treatment modification. ADVERSE REACTIONS The most common (incidence greater-than or equal to 10%, any severity) and/or treatment-emergent (Grade 2-4, occurring in greater-than or equal to 5% of subjects) adverse reactions occurring in subjects treated with efavirenz, emtricitabine and tenofovir DF in Study 934 through 144 weeks include diarrhea, nausea, fatigue, sinusitis, upper respiratory tract infections, nasopharyngitis, headache, dizziness, depression, insomnia, abnormal dreams and rash. DRUG INTERACTIONS Didanosine (ddI): tenofovir disoproxil fumarate increases ddI concentrations. Use with caution and monitor for evidence of ddI toxicity (eg, pancreatitis, neuropathy) when coadministered. The ddI dose should be reduced to 250 mg for patients weighing >60 kg. Data are not available to recommend a dose adjustment of ddI for patients weighing <60 kg. Coadministration of didanosine buffered tablet formulation with Truvada should be under fasted conditions.
Atazanavir (ATV): coadministration decreases ATV concentrations and increases tenofovir concentrations. ATV 300 mg should be boosted with ritonavir 100 mg only and taken with food when administered with Truvada. Monitor for evidence of tenofovir-associated adverse reactions and discontinue Truvada if appropriate. ATV without ritonavir should not be coadministered with Truvada.
Lopinavir/ritonavir (LPV/r): coadministration increases tenofovir concentrations. Patients receiving LPV/r and Truvada should be monitored for tenofovir-associated adverse reactions and discontinue Truvada if appropriate.
DOSAGE AND ADMINISTRATION
Recommended dose: one tablet (containing 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate) once daily taken orally with or without food in adults and pediatric patients 12 years of age and older with body weight greater than or equal to 35 kg (greater than or equal to 77 lb.).
Renal dosing guidelines
Creatinine clearance
(mL/min)a
greater-than or equal to 50 30-49
<30
(including patients
requiring hemodialysis)
Recommended
dosing
Every 24 hours Every 48 hours
Truvada should not be
administered
aCalculated using ideal (lean) body weight.
The safety and effectiveness of these dosing interval adjustment recommendations have not been clinically evaluated in patients with moderate renal impairment; clinical response to treatment and renal function should be closely monitored in these patients.
Please see full Prescribing Information for Complera and Truvada (including BOXED WARNINGS).
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Asia Pacific.
Forward-Looking Statement
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors, including the risk that physicians may not see advantages of Complera over other therapies and may therefore be reluctant to prescribe the product, and payers may be reluctant to approve or provide reimbursement for the product. In addition, pending marketing applications such as those in the European Union may not be approved or approval may be delayed, and marketing approval, if granted, may have significant limitations on its use. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Quarterly Report on Form 10-Q for the quarter ended June 30, 2011, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
U.S. full prescribing information for Complera is available at www.Gilead.com.
U.S. full prescribing information for Truvada is available at www.Truvada.com.
U.S. full prescribing information for Atripla is available at www.Atripla.com.
Complera, Truvada, Viread, Emtriva and Hepsera are trademarks or registered trademarks of Gilead Sciences, Inc. or its related companies.
Edurant is a trademark of Tibotec Pharmaceuticals.
Atripla is a registered trademark of Bristol-Myers Squibb & Gilead Sciences, LLC.
For more information on Gilead Sciences, please visit the company's website at www.gilead.com or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
SOURCE: Gilead Sciences, Inc.
Gilead Sciences, Inc.
Susan Hubbard, 650-522-5715 (Investors)
Erin Rau, 650-522-5635 (Media)
1. "The observed virologic failure rate in rilpivirine-treated subjects conferred a higher rate of overall treatment resistance and cross-resistance to the NNRTI class compared to efavirenz."
2. "More subjects treated with rilpivirine developed lamivudine/emtricitabine associated resistance compared to efavirenz."
This essentially means that a patient becoming resistant to either the Truvada or Edurant portion of the regimen would potentially have less options for sequential therapy down the line compared to the efavirenz-containing regimen used in the control arm of the Complera studies.
The rilpivirine-portion of the drug also appears to be heavily effected by gastric PH and potential for drug-drug interactions involving CYP3A which may lower rilpivirine to sub-therapeutic levels and potentially be a mechanism of resistance )
U.S. Food and Drug Administration Approves Gilead Sciences’ Complera™, a New Complete Once-Daily, Single-Tablet Regimen for HIV-1 Infection in Treatment-Naïve Adults
- Complera Combines the Most-Prescribed HIV Product in the United States with the Newest Antiretroviral Agent Approved by the FDA -
- Approval Marks Gilead's Second Successful Collaboration to Develop a Complete Single-Tablet Regimen for HIV/AIDS -
FOSTER CITY, Calif., Aug 10, 2011 (BUSINESS WIRE) --
Gilead Sciences, Inc. (Nasdaq:GILD) today announced that the U.S. Food and Drug Administration (FDA) has approved Complera(TM) (emtricitabine/rilpivirine/tenofovir disoproxil fumarate), a complete single-tablet regimen for the treatment of HIV-1 infection in treatment-naïve adults. Complera combines three antiretroviral medications in one daily tablet - Gilead's Truvada(R), which is a fixed-dose combination of the two nucleoside reverse transcriptase inhibitors emtricitabine and tenofovir disoproxil fumarate, and Tibotec Pharmaceuticals' non-nucleoside reverse transcriptase inhibitor, rilpivirine (marketed as Edurant(TM) in the United States by Janssen Therapeutics, Division of Janssen Products, LP). Truvada and rilpivirine were approved by the FDA in August 2004 and May 2011, respectively, for use as part of HIV combination therapy.
"In the 30 years since the first AIDS cases were reported, we've made incredible strides in the treatment of this disease," said Tony Mills, MD, Director of Medical Research, Anthony Mills MD, Inc. and a participating investigator in ongoing Complera studies. "The concept of a single-tablet regimen has become a goal in HIV drug development, and the standard of care in medical practice in the United States. However, no one therapy is appropriate for all patients. Given its efficacy, safety and convenience, the availability of Complera represents an exciting milestone in addressing the individual needs of patients new to HIV therapy."
The approval of Complera is supported by 48-week data from two Phase 3 double-blind, active controlled, randomized studies (ECHO and THRIVE) conducted by Tibotec that evaluated the safety and efficacy of rilpivirine compared to efavirenz among treatment-naïve HIV-1 infected adults. Both arms of the study were administered with a background regimen, in which the majority of patients in the rilpivirine arm received Truvada. A bioequivalence study, conducted by Gilead, demonstrated that the co-formulated single-tablet regimen achieved the same levels of medication in the blood as emtricitabine plus rilpivirine plus tenofovir disoproxil fumarate.
"Complera is the second complete single-tablet regimen that Gilead has introduced, and it represents a collaboration between two organizations that share a vision of simplifying HIV therapy for patients," said John C. Martin, PhD, Chairman and Chief Executive Officer, Gilead Sciences. "Tremendous progress has been made in the field of HIV, but we recognize new therapies are still needed, and we continue to work to advance options that address the needs of patients."
Complera is the second complete antiretroviral treatment regimen for HIV-1 available to treatment-naïve patients in a single once-daily pill. The first, Atripla(R) (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg), is marketed by Gilead and Bristol-Myers Squibb. Complera does not cure HIV-1 infection or help prevent the transmission of HIV to others. Complera has Boxed Warnings including lactic acidosis/severe hepatomegaly with steatosis and post treatment acute exacerbation of hepatitis B; see below for additional important safety information. The following points should be considered when initiating therapy with Complera:
More rilpivirine-treated subjects with HIV-1 RNA greater than 100,000 copies/mL at the start of therapy experienced virologic failure compared to subjects with HIV-1 RNA less than 100,000 copies/mL at the start of therapy.
The observed virologic failure rate in rilpivirine-treated subjects conferred a higher rate of overall treatment resistance and cross-resistance to the NNRTI class compared to efavirenz.
More subjects treated with rilpivirine developed lamivudine/emtricitabine associated resistance compared to efavirenz.
Complera is not recommended for patients less than 18 years of age.
Gilead first entered into a license and collaboration agreement with Tibotec for the development and commercialization of Complera in July 2009. Under the terms of the agreement, Gilead will assume the lead role in the manufacturing, registration, distribution and commercialization of Complera in the United States, Canada, Brazil, the European Union, Australia and New Zealand. Tibotec will be responsible for the commercialization of rilpivirine as a stand-alone product and will hold rights to co-detail Complera in these territories. A marketing application for the emtricitabine/rilpivirine/tenofovir disoproxil fumarate single-tablet regimen is currently pending in the European Union.
The companies also have finalized an agreement for the development and commercialization of the single-tablet regimen for the rest of world, including the developing world. Gilead will be responsible for the registration, distribution and commercialization of the single-tablet regimen in certain European countries, Latin America and the Caribbean. Tibotec will be responsible for all countries outside of the Gilead territories, the most significant of which include Asia Pacific, including Japan, the Middle East, Eastern Europe and all of Africa.
Important Product Safety Information About Complera, Including Boxed Warnings
BOXED WARNINGS: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including tenofovir disoproxil fumarate, a component of Complera, in combination with other antiretrovirals.
Complera is not approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of Complera have not been established in patients coinfected with HBV and HIV-1.Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued Emtriva or Viread, which are components of Complera.Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue Complera.If appropriate, initiation of anti-hepatitis B therapy may be warranted.
CONTRAINDICATIONS
Complera should not be co-administered with the following drugs, as significant decreases in rilpivirine plasma concentrations may occur due to CYP3A enzyme induction or gastric pH increase, which may result in loss of virologic response and possible resistance to Complera or to the class of NNRTIs:
the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin
the antimycobacterials rifabutin, rifampin, rifapentine
proton pump inhibitors, such as esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole
the glucocorticoid systemic dexamethasone (more than a single dose)
St John's wort (Hypericum perforatum)
WARNINGS AND PRECAUTIONS
New onset or worsening renal impairment
Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of tenofovir disoproxil fumarate. Assess creatinine clearance (CrCl) before initiating treatment with Complera. Monitor CrCl and serum phosphorus in patients at risk for renal impairment, including patients who have previously experienced renal events while receiving Hepsera(R) (adefovir dipivoxil). Avoid administering Complera with concurrent or recent use of nephrotoxic drugs. Patients with CrCl below 50 mL per minute should not receive Complera.
Drug Interactions
Complera should be used with caution when given with drugs that may reduce the exposure of rilpivirine.
Complera should be used with caution when co-administered with a drug with a known risk of Torsade de Pointes.
Depressive Disorders
The adverse reaction depressive disorders (depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, suicidal ideation) has been reported with rilpivirine. During the Phase 3 trials (N = 1,368), the incidence of depressive disorders (regardless of causality, severity) reported among rilpivirine (N = 686) or efavirenz (N = 682) was 8% and 6%, respectively. Most events were mild or moderate in severity. The incidence of Grade 3 and 4 depressive disorders (regardless of causality) was 1% for both rilpivirine and efavirenz. The incidence of discontinuation due to depressive disorders among rilpivirine or efavirenz was 1% in each arm. Suicide attempt was reported in 2 subjects in the rilpivirine arm while suicide ideation was reported in 1 subject in the rilpivirine arm and in 3 subjects in the efavirenz arm. Patients with severe depressive symptoms should seek immediate medical evaluation to assess the possibility that the symptoms are related to Complera, and if so, to determine whether the risks of continued therapy outweigh the benefits.
Decreases in bone mineral density
Bone mineral density (BMD) monitoring should be considered for patients who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Cases of osteomalacia (associated with proximal renal tubulopathy and which may contribute to fractures) have been reported in association with the use of tenofovir disoproxil fumarate.
Co-administration with other products
Complera should not be administered concurrently with other medicinal products containing any of the same active components, emtricitabine, rilpivirine, or tenofovir disoproxil fumarate (Emtriva, Edurant, Viread, Truvada, Atripla), with medicinal products containing lamivudine (Epivir, Epivir-HBV, Epzicom, Combivir, Trizivir), or with adefovir dipivoxil (Hepsera).
Fat redistribution
Redistribution/accumulation of body fat has been observed in patients receiving antiretroviral therapy.
Immune reconstitution syndrome
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including the components of Complera. Further evaluation and treatment may be necessary.
ADVERSE REACTIONS
The most common adverse drug reactions to rilpivirine (incidence greater than or equal to 2%, Grades 2-4) were insomnia and headache.
The most common adverse drug reactions to emtricitabine and tenofovir disoproxil fumarate (incidence greater-than or equal to 10%) were diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash.
DRUG INTERACTIONS
Complera should not be used with drugs where significant decreases in rilpivirine plasma concentrations may occur (See CONTRAINDICATIONS).
Complera is a complete regimen for the treatment of HIV-1 infection; therefore Complera should not be administered with other antiretroviral medications for the treatment of HIV-1 infection.
Drugs inducing or inhibiting CYP3A enzymes: Rilpivirine is primarily metabolized by cytochrome P450 (CYP) 3A, and drugs that induce or inhibit CYP3A may thus affect the clearance of rilpivirine. Coadministration of rilpivirine and drugs that induce CYP3A may result in decreased plasma concentrations of rilpivirine and loss of virologic response and possible resistance to rilpivirine or to the class of NNRTIs. Coadministration of rilpivirine and drugs that inhibit CYP3A may result in increased plasma concentrations of rilpivirine.
Drugs increasing gastric PH: Coadministration of rilpivirine with drugs that increase gastric pH may decrease plasma concentrations of rilpivirine and loss of virologic response and possible resistance to rilpivirine or to the class of NNRTIs.
Drugs affecting renal function: Since emtricitabine and tenofovir are primarily eliminated by the kidneys, coadministration of Complera with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of emtricitabine, tenofovir, and/or other renally eliminated drugs. Some examples include, but are not limited to, acyclovir, adefovir dipivoxil, cidofovir, ganciclovir, valacyclovir and valganciclovir.
QT prolonging drugs: There is limited information available on the potential for a pharmacodynamic interaction between rilpivirine and drugs that prolong the QTc interval of the electrocardiogram. In a study of healthy subjects, supratherapeutic doses of rilpivirine (75 mg once daily and 300 mg once daily) have been shown to prolong the QTc interval of the electrocardiogram. Complera should be used with caution when coadministered with a drug with a known risk of Torsade de Pointes.
DOSAGE AND ADMINISTRATION
Adults: The recommended dose of Complera is one tablet taken orally once daily with a meal.
Renal Impairment: Because Complera is a fixed-dose combination, it should not be prescribed for patients requiring dose adjustment such as those with moderate or severe renal impairment (creatinine clearance below 50 mL per minute).
Important Safety Product Information About Truvada, Including Boxed Warnings
Truvada, a combination of Emtriva (emtricitabine) and Viread (tenofovir disoproxil fumarate [DF]), is indicated in combination with other antiretroviral agents (such as non nucleoside reverse transcriptase inhibitors or protease inhibitors) for the treatment of HIV-1 infection.
The following points should be considered when initiating therapy with Truvada for the treatment of HIV-1 infection:
It is not recommended that Truvada be used as a component of a triple nucleoside regimen.
Truvada should not be coadministered with Atripla (efavirenz/emtricitabine/tenofovir DF), Emtriva, Viread, or lamivudine-containing products.
In treatment-experienced patients, the use of Truvada should be guided by laboratory testing and treatment history.
WARNINGS: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including Viread, a component of Truvada, in combination with other antiretrovirals.
Truvada is not approved for the treatment of chronic hepatitis B virus (HBV) infection, and the safety and efficacy of Truvada have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued Truvada. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue Truvada. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
WARNINGS AND PRECAUTIONS
New Onset or Worsening Renal Impairment
Emtricitabine and tenofovir are principally eliminated by the kidney. Renal impairment, including acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of tenofovir DF.
Assess CrCl before initiating treatment with Truvada. Routinely monitor CrCl and serum phosphorus in patients at risk for renal impairment, including patients who have previously experienced renal events while receiving Hepsera (adefovir dipivoxil).
Dosing interval adjustment of Truvada and close monitoring of renal function are recommended in all patients with CrCl 30-49 mL/min. No safety or efficacy data are available in patients with renal impairment who received Truvada using these dosing guidelines, so the potential benefit of Truvada therapy should be assessed against the potential risk of renal toxicity. Truvada should not be administered in patients with CrCl <30 mL/min or patients requiring hemodialysis. Avoid administering Truvada with concurrent or recent use of nephrotoxic drugs. Coadministration With Other Products Since Truvada contains emtricitabine and tenofovir DF, Truvada should not be coadministered with Atripla, Emtriva or Viread. Due to similarities between emtricitabine and lamivudine, Truvada should not be coadministered with other drugs containing lamivudine, including Combivir (zidovudine/lamivudine) Epivir or Epivir-HBV (lamivudine), Epzicom (abacavir sulfate/lamivudine), or Trizivir (abacavir sulfate/lamivudine/zidovudine). Truvada should not be administered with Hepsera. Bone Mineral Density Decreases in bone mineral density (BMD): BMD monitoring should be considered for HIV-1 infected patients who have a history of pathologic bone fracture or who are at risk for osteopenia. Cases of osteomalacia (associated with proximal renal tubulopathy and which may contribute to fractures) have been reported in association with the use of Viread. Fat Redistribution Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established. Immune Reconstitution Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including Truvada, which may necessitate further evaluation and treatment. Early Virologic Failure Triple nucleoside-only regimens: Early virologic failure has been reported in HIV-infected patients on regimens containing only 3 nucleoside reverse transcriptase inhibitors (NRTIs). Monitor carefully and consider treatment modification. ADVERSE REACTIONS The most common (incidence greater-than or equal to 10%, any severity) and/or treatment-emergent (Grade 2-4, occurring in greater-than or equal to 5% of subjects) adverse reactions occurring in subjects treated with efavirenz, emtricitabine and tenofovir DF in Study 934 through 144 weeks include diarrhea, nausea, fatigue, sinusitis, upper respiratory tract infections, nasopharyngitis, headache, dizziness, depression, insomnia, abnormal dreams and rash. DRUG INTERACTIONS Didanosine (ddI): tenofovir disoproxil fumarate increases ddI concentrations. Use with caution and monitor for evidence of ddI toxicity (eg, pancreatitis, neuropathy) when coadministered. The ddI dose should be reduced to 250 mg for patients weighing >60 kg. Data are not available to recommend a dose adjustment of ddI for patients weighing <60 kg. Coadministration of didanosine buffered tablet formulation with Truvada should be under fasted conditions.
Atazanavir (ATV): coadministration decreases ATV concentrations and increases tenofovir concentrations. ATV 300 mg should be boosted with ritonavir 100 mg only and taken with food when administered with Truvada. Monitor for evidence of tenofovir-associated adverse reactions and discontinue Truvada if appropriate. ATV without ritonavir should not be coadministered with Truvada.
Lopinavir/ritonavir (LPV/r): coadministration increases tenofovir concentrations. Patients receiving LPV/r and Truvada should be monitored for tenofovir-associated adverse reactions and discontinue Truvada if appropriate.
DOSAGE AND ADMINISTRATION
Recommended dose: one tablet (containing 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate) once daily taken orally with or without food in adults and pediatric patients 12 years of age and older with body weight greater than or equal to 35 kg (greater than or equal to 77 lb.).
Renal dosing guidelines
Creatinine clearance
(mL/min)a
greater-than or equal to 50 30-49
<30
(including patients
requiring hemodialysis)
Recommended
dosing
Every 24 hours Every 48 hours
Truvada should not be
administered
aCalculated using ideal (lean) body weight.
The safety and effectiveness of these dosing interval adjustment recommendations have not been clinically evaluated in patients with moderate renal impairment; clinical response to treatment and renal function should be closely monitored in these patients.
Please see full Prescribing Information for Complera and Truvada (including BOXED WARNINGS).
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Asia Pacific.
Forward-Looking Statement
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors, including the risk that physicians may not see advantages of Complera over other therapies and may therefore be reluctant to prescribe the product, and payers may be reluctant to approve or provide reimbursement for the product. In addition, pending marketing applications such as those in the European Union may not be approved or approval may be delayed, and marketing approval, if granted, may have significant limitations on its use. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Quarterly Report on Form 10-Q for the quarter ended June 30, 2011, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
U.S. full prescribing information for Complera is available at www.Gilead.com.
U.S. full prescribing information for Truvada is available at www.Truvada.com.
U.S. full prescribing information for Atripla is available at www.Atripla.com.
Complera, Truvada, Viread, Emtriva and Hepsera are trademarks or registered trademarks of Gilead Sciences, Inc. or its related companies.
Edurant is a trademark of Tibotec Pharmaceuticals.
Atripla is a registered trademark of Bristol-Myers Squibb & Gilead Sciences, LLC.
For more information on Gilead Sciences, please visit the company's website at www.gilead.com or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
SOURCE: Gilead Sciences, Inc.
Gilead Sciences, Inc.
Susan Hubbard, 650-522-5715 (Investors)
Erin Rau, 650-522-5635 (Media)
Thursday, July 7, 2011
Medivir/Tibotec's HCV protease inhibitor TMC435 receives FDA 'Fast-Track' status...
Medivir: TMC435 has Received Fast Track Designation from the FDA and TMC435 will be studied in combination with Pharmasset's PSI-7977 for HCV genotype-1
HUDDINGE, Sweden, Jul 06, 2011 (BUSINESS WIRE) -- Regulatory News:
Medivir AB (sto:MVIRB)(omx:MVIR), is an emerging research-based specialty pharmaceutical company focused on infectious diseases.
Medivir today announced that its investigational protease inhibitor TMC435 has received "Fast Track" designation by the U.S. Food and Drug Administration ("FDA") for the treatment of chronic hepatitis C (CHC) genotype-1 infection. This is based on TMC435's potential to address unmet medical needs in the treatment of CHC infection compared to currently approved therapies.
TMC435 may offer:
-- High sustained virological response (SVR) rates in genotype-1 HCV-infected patients, including hard-to-treat subgroups
-- Short treatment duration
-- Favorable overall safety and tolerability profile
-- A convenient once-daily (q.d.) dosing regimen
Furthermore, Medivir also confirms the intention to start a proof-of-concept oral, interferon-free phase 2 trial, investigating the combination of TMC435, a once daily NS3/4A protease inhibitor (PI) for the treatment of genotype-1 chronic hepatitis C virus (HCV) infection and Pharmasset's PSI-7977, a once daily nucleotide NS5B polymerase inhibitor. The phase 2 study, which is being managed by Tibotec Pharmaceuticals, will investigate the efficacy and safety of 12 weeks or 24 weeks of TMC435 150 mg q.d. in combination with PSI-7977 400 mg q.d. with or without ribavirin in prior null responders to peginterferon/ribavirin therapy. The primary endpoint of the trial will be sustained virological response at 12 weeks (SVR12).
Bertil Samuelsson, CSO, of Medivir commented, "We are delighted to have received the Fast Track designation for TMC435 from the FDA. This shows that TMC435 with its high safety profile, efficacy, short treatment duration and convenience of once daily dosing is believed to have the potential to provide benefit over current treatments. We believe TMC435 has the potential to become a cornerstone of future direct-acting antiviral combinations for HCV therapy. We are thus very pleased over the clinical collaboration agreement Pharmasset announced today with Tibotec, and the coming start-up of a TMC435 combination trial with Pharmasset's once daily NS5B nucleotide inhibitor PSI-7977. This is one of several ongoing TMC435 combination trials and we expect the momentum to continue with regards to the development of TMC435"
About Fast Track
Fast Track is a process designed to facilitate the development, and expedite the review of drugs to treat serious diseases and to fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious diseases. "Filling an unmet medical need" is defined as providing a therapy where none exists or providing a therapy that may potentially be superior to existing therapy. If there are existing therapies, a fast track drug must show some advantage over available treatment, such as:
-- Showing superior effectiveness
-- Avoiding serious side effects of an available treatment
-- Improving the diagnosis of a serious disease where early diagnosis results in an improved outcome
-- Decreasing a clinically significant toxicity of an accepted treatment
A drug that receives Fast Track designation is eligible for some or all of the following:
-- More frequent meetings with the FDA to discuss the drug's development plan and ensure collection of appropriate data needed to support drug approval
-- More frequent written correspondence from the FDA about such things as the design of the proposed clinical trials
-- Eligibility for Accelerated Approval, i.e., approval on an effect on a surrogate or substitute endpoint reasonably likely to predict clinical benefit
-- Rolling Review, which means that a drug company can submit completed sections of its New Drug Application (NDA) for review by FDA, rather than waiting until every section of the application is completed before the entire application can be reviewed. NDA review usually does not begin until the drug company has submitted the entire application to the FDA
-- Dispute resolution if the drug company is not satisfied with an FDA decision not to grant Fast Track status.
In addition, most drugs that are eligible for Fast Track designation are likely to be considered appropriate to receive a Priority Review.
Once a drug receives Fast Track designation, early and frequent communication between the FDA and a drug company is encouraged throughout the entire drug development and review process. The frequency of communication assures that questions and issues are resolved quickly, often leading to earlier drug approval and access by patients.
About TMC435
TMC435, an investigational CHC protease inhibitor currently in phase 3 clinical development, is a highly potent, selective and safe once-daily (q.d.) drug jointly developed by Tibotec Pharmaceuticals to treat chronic hepatitis C virus infections.
TMC435 is being developed in combination with PegIFN/RBV and in combination with Direct-acting Antiviral (DAA) agents without peginterferon and with or without ribavirin (RBV). In June 2011 the combination study of TMC435 with TMC647055, a non-nucleoside NS5B polymerase inhibitor being developed by Tibotec Pharmaceuticals, was initiated.
Three global clinical phase 3 response guided studies were initiated in early 2011 by Tibotec:
-- TMC435-C208 or QUEST-1 includes approximately 375 treatment-naive patients
-- TMC435-C216 or QUEST-2 includes approximately 375 treatment-naive patients
-- TMC435-C3007 or PROMISE includes approximately 375 who have relapsed after prior interferon-based treatment
Phase 3 programs for TMC435 are also ongoing in Japan.
In parallel with the recent start of the global phase 3-studies, TMC435 is currently in a follow up phase in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naive and in G1 patients that failed previous IFN-based treatment. More safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2011.
For additional information from these studies, please see www.medivir.com and www.clinicaltrials.gov
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The US Centers for Disease Control ("CDC") has reported that almost three million people in the United States are chronically infected with HCV.
About Medivir
Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company's key pipeline asset is TMC435, a novel protease inhibitor is in phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals. In June 2011, Medivir acquired the specialty pharmaceutical company BioPhausia to ensure timely commercialization of TMC435 in the Nordic markets, once approved.
Medivir's first product, the unique cold sore product Xerese(TM)/Xerclear(R) was launched on the US market in February 2011. Xerese(TM)/Xerclear(R), which has been approved in both the US and Europe is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia. Rights in North America, Canada and Mexico have recently been sold to Meda AB. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.
For more information about Medivir, please visit the Company's website: www.medivir.com .
This information was brought to you by Cision http://www.cisionwire.com
SOURCE: Medivir
HUDDINGE, Sweden, Jul 06, 2011 (BUSINESS WIRE) -- Regulatory News:
Medivir AB (sto:MVIRB)(omx:MVIR), is an emerging research-based specialty pharmaceutical company focused on infectious diseases.
Medivir today announced that its investigational protease inhibitor TMC435 has received "Fast Track" designation by the U.S. Food and Drug Administration ("FDA") for the treatment of chronic hepatitis C (CHC) genotype-1 infection. This is based on TMC435's potential to address unmet medical needs in the treatment of CHC infection compared to currently approved therapies.
TMC435 may offer:
-- High sustained virological response (SVR) rates in genotype-1 HCV-infected patients, including hard-to-treat subgroups
-- Short treatment duration
-- Favorable overall safety and tolerability profile
-- A convenient once-daily (q.d.) dosing regimen
Furthermore, Medivir also confirms the intention to start a proof-of-concept oral, interferon-free phase 2 trial, investigating the combination of TMC435, a once daily NS3/4A protease inhibitor (PI) for the treatment of genotype-1 chronic hepatitis C virus (HCV) infection and Pharmasset's PSI-7977, a once daily nucleotide NS5B polymerase inhibitor. The phase 2 study, which is being managed by Tibotec Pharmaceuticals, will investigate the efficacy and safety of 12 weeks or 24 weeks of TMC435 150 mg q.d. in combination with PSI-7977 400 mg q.d. with or without ribavirin in prior null responders to peginterferon/ribavirin therapy. The primary endpoint of the trial will be sustained virological response at 12 weeks (SVR12).
Bertil Samuelsson, CSO, of Medivir commented, "We are delighted to have received the Fast Track designation for TMC435 from the FDA. This shows that TMC435 with its high safety profile, efficacy, short treatment duration and convenience of once daily dosing is believed to have the potential to provide benefit over current treatments. We believe TMC435 has the potential to become a cornerstone of future direct-acting antiviral combinations for HCV therapy. We are thus very pleased over the clinical collaboration agreement Pharmasset announced today with Tibotec, and the coming start-up of a TMC435 combination trial with Pharmasset's once daily NS5B nucleotide inhibitor PSI-7977. This is one of several ongoing TMC435 combination trials and we expect the momentum to continue with regards to the development of TMC435"
About Fast Track
Fast Track is a process designed to facilitate the development, and expedite the review of drugs to treat serious diseases and to fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious diseases. "Filling an unmet medical need" is defined as providing a therapy where none exists or providing a therapy that may potentially be superior to existing therapy. If there are existing therapies, a fast track drug must show some advantage over available treatment, such as:
-- Showing superior effectiveness
-- Avoiding serious side effects of an available treatment
-- Improving the diagnosis of a serious disease where early diagnosis results in an improved outcome
-- Decreasing a clinically significant toxicity of an accepted treatment
A drug that receives Fast Track designation is eligible for some or all of the following:
-- More frequent meetings with the FDA to discuss the drug's development plan and ensure collection of appropriate data needed to support drug approval
-- More frequent written correspondence from the FDA about such things as the design of the proposed clinical trials
-- Eligibility for Accelerated Approval, i.e., approval on an effect on a surrogate or substitute endpoint reasonably likely to predict clinical benefit
-- Rolling Review, which means that a drug company can submit completed sections of its New Drug Application (NDA) for review by FDA, rather than waiting until every section of the application is completed before the entire application can be reviewed. NDA review usually does not begin until the drug company has submitted the entire application to the FDA
-- Dispute resolution if the drug company is not satisfied with an FDA decision not to grant Fast Track status.
In addition, most drugs that are eligible for Fast Track designation are likely to be considered appropriate to receive a Priority Review.
Once a drug receives Fast Track designation, early and frequent communication between the FDA and a drug company is encouraged throughout the entire drug development and review process. The frequency of communication assures that questions and issues are resolved quickly, often leading to earlier drug approval and access by patients.
About TMC435
TMC435, an investigational CHC protease inhibitor currently in phase 3 clinical development, is a highly potent, selective and safe once-daily (q.d.) drug jointly developed by Tibotec Pharmaceuticals to treat chronic hepatitis C virus infections.
TMC435 is being developed in combination with PegIFN/RBV and in combination with Direct-acting Antiviral (DAA) agents without peginterferon and with or without ribavirin (RBV). In June 2011 the combination study of TMC435 with TMC647055, a non-nucleoside NS5B polymerase inhibitor being developed by Tibotec Pharmaceuticals, was initiated.
Three global clinical phase 3 response guided studies were initiated in early 2011 by Tibotec:
-- TMC435-C208 or QUEST-1 includes approximately 375 treatment-naive patients
-- TMC435-C216 or QUEST-2 includes approximately 375 treatment-naive patients
-- TMC435-C3007 or PROMISE includes approximately 375 who have relapsed after prior interferon-based treatment
Phase 3 programs for TMC435 are also ongoing in Japan.
In parallel with the recent start of the global phase 3-studies, TMC435 is currently in a follow up phase in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naive and in G1 patients that failed previous IFN-based treatment. More safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2011.
For additional information from these studies, please see www.medivir.com and www.clinicaltrials.gov
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The US Centers for Disease Control ("CDC") has reported that almost three million people in the United States are chronically infected with HCV.
About Medivir
Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company's key pipeline asset is TMC435, a novel protease inhibitor is in phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals. In June 2011, Medivir acquired the specialty pharmaceutical company BioPhausia to ensure timely commercialization of TMC435 in the Nordic markets, once approved.
Medivir's first product, the unique cold sore product Xerese(TM)/Xerclear(R) was launched on the US market in February 2011. Xerese(TM)/Xerclear(R), which has been approved in both the US and Europe is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia. Rights in North America, Canada and Mexico have recently been sold to Meda AB. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.
For more information about Medivir, please visit the Company's website: www.medivir.com .
This information was brought to you by Cision http://www.cisionwire.com
SOURCE: Medivir
Wednesday, July 6, 2011
Pharmasset & Tibotec team up HCV drugs in clinical collaborative agreement...
Pharmasset all over the news this week, they definitely seem to be teaming up with the right folks in their development of their nucleotide analog PSI-7977... with their own nuc PSI-938, with BMS's NS5a inhibitor and now with Medivir/Tibotec's TMC435. The HCV DAA development space is definitely heating up!
Pharmasset Enters into a Clinical Collaboration Agreement with Tibotec Pharmaceuticals for a Combination Study in Patients Chronically Infected with Hepatitis C
- Study to evaluate the combination of PSI-7977 and TMC435 with and without ribavirin in prior null responder, genotype 1 HCV patients
PRINCETON, N.J., July 6, 2011 /PRNewswire/ -- Pharmasset, Inc. (NASDAQ: VRUS), announced today that it has entered into a clinical collaboration agreement with Tibotec Pharmaceuticals to evaluate in a Phase 2 study the safety and efficacy of PSI-7977, Pharmasset's investigational nucleotide polymerase inhibitor, in combination with TMC435, Tibotec Pharmaceuticals' investigational protease inhibitor, for the treatment of chronic hepatitis C virus (HCV).
This phase 2 proof of concept study will evaluate the potential to achieve sustained virologic response 12 weeks post treatment with an all oral, once-daily, interferon-free treatment regimen in patients infected with genotype 1 HCV. Specifically, the study will assess the safety, pharmacokinetics and pharmacodynamics of 12 and 24 weeks of PSI-7977 in combination with TMC435, with and without ribavirin, in patients chronically infected with HCV genotype 1 who had a prior null response to peginterferon alfa and ribavirin treatment. The study is planned to start in the second half of 2011.
"We are excited to be working with Tibotec to simplify and improve HCV treatment," stated Bill Symonds, PharmD, Pharmasset's Senior Vice President of Clinical Pharmacology and Translational Medicine. "PSI-7977 is now being studied in interferon-free combinations with each of the three leading classes of direct-acting antivirals: Tibotec's protease inhibitor, Bristol-Myers Squibb's NS5a inhibitor, and our own nucleotide, PSI-938. This advances one of our key goals at Pharmasset: to develop our nucleotide analogs as the backbone of interferon-free HCV therapy."
About PSI-7977
PSI-7977 is a prodrug of a uracil nucleotide analog polymerase inhibitor we are developing for the treatment of chronic HCV infection. PSI-7977 has completed a 28 day phase 2a trial in combination with peg-interferon and ribavirin (Peg-IFN/RBV) and is currently being tested in four phase 2b studies: the PROTON trial in combination with peg-IFN/RBV in HCV genotype 1, 2 or 3 patients; the ATOMIC trial with peg-IFN/RBV in HCV genotypes 1,4,5,6; the ELECTRON trial, an interferon sparing /interferon free study in HCV genotypes 1,2 and 3 and a study with Bristol-Myers Squibb's NS5a inhibitor, BMS-790052, as part of an interferon free regimen. Pharmasset also anticipates initiating its own interferon free trial with PSI-7977 and PSI-938, a guanine nucleotide polymerase inhibitor in the third calendar quarter 2011.
About Pharmasset
Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing, and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is the development of oral therapeutics for the treatment of hepatitis C virus (HCV) infection. Our research and development efforts are focused on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have three clinical-stage product candidates advancing in trials in various populations. Our pyrimidine, PSI-7977, an unpartnered uracil nucleotide analog, is currently under study in three Phase 2b trials in patients with HCV genotypes 1 through 6, including abbreviated duration interferon and interferon-free regimens. Our purine, PSI-938, an unpartnered guanosine nucleotide analog, recently reported safety and efficacy data from 14 days of monotherapy as well as 14 days in combination with the pyrimidine, PSI-7977. An SVR-endpoint study of the purine-pyrimidine combination is anticipated to begin in the third quarter of 2011. Mericitabine (RG7128) continues in two Phase 2b trials and one interferon-free trial being conducted through a strategic collaboration with Roche.
Pharmasset
Richard E. T. Smith, Ph.D.
VP, Investor Relations and Corporate Communications
Office: +1 (609) 865-0693
Pharmasset Forward-Looking Statements
Pharmasset "Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release that are not historical facts are "forward-looking statements," that involve risks, uncertainties, and other important factors, including, without limitation, the risk of cessation or delay of any of the ongoing or planned clinical trials and/or our development of our product candidates, the risk that the results of previously conducted studies involving our product candidates will not be repeated or observed in ongoing or future studies involving our product candidates, the risk that our collaboration with Roche will not continue or will not be successful, and the risk that any one or more of our product candidates will not be successfully developed and commercialized. For a discussion of risks, uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our Annual Report on Form 10-K for the fiscal year ended September 30, 2010 and our Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission.
SOURCE Pharmasset, Inc.
RELATED LINKS
http://www.pharmasset.com
Pharmasset Enters into a Clinical Collaboration Agreement with Tibotec Pharmaceuticals for a Combination Study in Patients Chronically Infected with Hepatitis C
- Study to evaluate the combination of PSI-7977 and TMC435 with and without ribavirin in prior null responder, genotype 1 HCV patients
PRINCETON, N.J., July 6, 2011 /PRNewswire/ -- Pharmasset, Inc. (NASDAQ: VRUS), announced today that it has entered into a clinical collaboration agreement with Tibotec Pharmaceuticals to evaluate in a Phase 2 study the safety and efficacy of PSI-7977, Pharmasset's investigational nucleotide polymerase inhibitor, in combination with TMC435, Tibotec Pharmaceuticals' investigational protease inhibitor, for the treatment of chronic hepatitis C virus (HCV).
This phase 2 proof of concept study will evaluate the potential to achieve sustained virologic response 12 weeks post treatment with an all oral, once-daily, interferon-free treatment regimen in patients infected with genotype 1 HCV. Specifically, the study will assess the safety, pharmacokinetics and pharmacodynamics of 12 and 24 weeks of PSI-7977 in combination with TMC435, with and without ribavirin, in patients chronically infected with HCV genotype 1 who had a prior null response to peginterferon alfa and ribavirin treatment. The study is planned to start in the second half of 2011.
"We are excited to be working with Tibotec to simplify and improve HCV treatment," stated Bill Symonds, PharmD, Pharmasset's Senior Vice President of Clinical Pharmacology and Translational Medicine. "PSI-7977 is now being studied in interferon-free combinations with each of the three leading classes of direct-acting antivirals: Tibotec's protease inhibitor, Bristol-Myers Squibb's NS5a inhibitor, and our own nucleotide, PSI-938. This advances one of our key goals at Pharmasset: to develop our nucleotide analogs as the backbone of interferon-free HCV therapy."
About PSI-7977
PSI-7977 is a prodrug of a uracil nucleotide analog polymerase inhibitor we are developing for the treatment of chronic HCV infection. PSI-7977 has completed a 28 day phase 2a trial in combination with peg-interferon and ribavirin (Peg-IFN/RBV) and is currently being tested in four phase 2b studies: the PROTON trial in combination with peg-IFN/RBV in HCV genotype 1, 2 or 3 patients; the ATOMIC trial with peg-IFN/RBV in HCV genotypes 1,4,5,6; the ELECTRON trial, an interferon sparing /interferon free study in HCV genotypes 1,2 and 3 and a study with Bristol-Myers Squibb's NS5a inhibitor, BMS-790052, as part of an interferon free regimen. Pharmasset also anticipates initiating its own interferon free trial with PSI-7977 and PSI-938, a guanine nucleotide polymerase inhibitor in the third calendar quarter 2011.
About Pharmasset
Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing, and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is the development of oral therapeutics for the treatment of hepatitis C virus (HCV) infection. Our research and development efforts are focused on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have three clinical-stage product candidates advancing in trials in various populations. Our pyrimidine, PSI-7977, an unpartnered uracil nucleotide analog, is currently under study in three Phase 2b trials in patients with HCV genotypes 1 through 6, including abbreviated duration interferon and interferon-free regimens. Our purine, PSI-938, an unpartnered guanosine nucleotide analog, recently reported safety and efficacy data from 14 days of monotherapy as well as 14 days in combination with the pyrimidine, PSI-7977. An SVR-endpoint study of the purine-pyrimidine combination is anticipated to begin in the third quarter of 2011. Mericitabine (RG7128) continues in two Phase 2b trials and one interferon-free trial being conducted through a strategic collaboration with Roche.
Pharmasset
Richard E. T. Smith, Ph.D.
VP, Investor Relations and Corporate Communications
Office: +1 (609) 865-0693
Pharmasset Forward-Looking Statements
Pharmasset "Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release that are not historical facts are "forward-looking statements," that involve risks, uncertainties, and other important factors, including, without limitation, the risk of cessation or delay of any of the ongoing or planned clinical trials and/or our development of our product candidates, the risk that the results of previously conducted studies involving our product candidates will not be repeated or observed in ongoing or future studies involving our product candidates, the risk that our collaboration with Roche will not continue or will not be successful, and the risk that any one or more of our product candidates will not be successfully developed and commercialized. For a discussion of risks, uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our Annual Report on Form 10-K for the fiscal year ended September 30, 2010 and our Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission.
SOURCE Pharmasset, Inc.
RELATED LINKS
http://www.pharmasset.com
Friday, May 20, 2011
FDA Approves Tibotec's New HIV Treatment, Edurant
FDA Approves Tibotec's New HIV Treatment, Edurant
5/20/2011
SILVER SPRING, Md., May 20, 2011 /PRNewswire-USNewswire/ -- The U.S. Food and Drug Administration today approved Edurant (rilpivirine) in combination with other antiretroviral drugs for the treatment of HIV-1 infection in adults who have never taken HIV therapy (treatment-naive).
Edurant belongs to a class of HIV drugs called non-nucleoside reverse transcriptase inhibitor (NNRTI). The drug works by blocking HIV viral replication. Edurant is to be used as part of a highly active antiretroviral therapy (HAART) regimen that is designed to suppress the amount of HIV (viral load) in the blood. Edurant is a pill taken once a day with food.
"Patients may respond differently to various HIV drugs or experience varied side effects. FDA's approval of Edurant provides an additional treatment option for patients who are starting HIV therapy," said Edward Cox, M.D., M.P.H, director, Office of Antimicrobial Products in the FDA's Center for Drug Evaluation and Research.
The safety and effectiveness of Edurant is based on 48-week data from two Phase 3 clinical trials with 1,368 adult subjects with HIV infection, and from a 96-week (with extension to 192 weeks) trial. Patients had not received prior HIV therapy and were selected to receive treatment with Edurant or efavirenz (another FDA-approved NNRTI for the treatment of HIV infection). Both drugs were given in combination with other antiretroviral drugs.
Edurant was as effective as efavirenz in lowering viral load. In the Edurant and efavirenz groups, 83 percent and 80 percent of subjects, respectively, had undetectable amounts of HIV in their blood after 48 weeks of treatment. Patients receiving Edurant who had a higher viral load at the start of therapy were more likely not to respond to the drug than were patients with a lower viral load at the start of therapy. In addition, persons who failed therapy with Edurant developed more drug resistance than patients who failed efavirenz.
The most commonly reported side effects in patients taking Edurant included depression, difficulty sleeping (insomnia), headache and rash. Fewer patients stopped taking the drug due to side effects as compared to patients taking efavirenz.
Edurant does not cure HIV infection. Patients must stay on continuous HIV therapy to control HIV infection and decrease HIV-related illnesses.
Edurant is manufactured by Raritan, N.J.-based Tibotec Therapeutics, a division of Centocor Ortho Biotech Inc.
For more information:
FDA: HIV and AIDS Activities
http://www.fda.gov/ForConsumers/byAudience/ForPatientAdvocates/HIVandAIDSActivities/default.htm
FDA: Antiretroviral drugs used in the treatment of HIV infection
http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm118915.htm
CDC: HIV/AIDS
http://www.cdc.gov/hiv/default.htm
HHS: AIDS News and Resources
http://www.aids.gov/
AIDS Information
http://www.aidsinfo.nih.gov/
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation's food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
Media Inquiries:Erica Jefferson, 301-796-4988, erica.jefferson@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA
SOURCE U.S. Food and Drug Administration
5/20/2011
SILVER SPRING, Md., May 20, 2011 /PRNewswire-USNewswire/ -- The U.S. Food and Drug Administration today approved Edurant (rilpivirine) in combination with other antiretroviral drugs for the treatment of HIV-1 infection in adults who have never taken HIV therapy (treatment-naive).
Edurant belongs to a class of HIV drugs called non-nucleoside reverse transcriptase inhibitor (NNRTI). The drug works by blocking HIV viral replication. Edurant is to be used as part of a highly active antiretroviral therapy (HAART) regimen that is designed to suppress the amount of HIV (viral load) in the blood. Edurant is a pill taken once a day with food.
"Patients may respond differently to various HIV drugs or experience varied side effects. FDA's approval of Edurant provides an additional treatment option for patients who are starting HIV therapy," said Edward Cox, M.D., M.P.H, director, Office of Antimicrobial Products in the FDA's Center for Drug Evaluation and Research.
The safety and effectiveness of Edurant is based on 48-week data from two Phase 3 clinical trials with 1,368 adult subjects with HIV infection, and from a 96-week (with extension to 192 weeks) trial. Patients had not received prior HIV therapy and were selected to receive treatment with Edurant or efavirenz (another FDA-approved NNRTI for the treatment of HIV infection). Both drugs were given in combination with other antiretroviral drugs.
Edurant was as effective as efavirenz in lowering viral load. In the Edurant and efavirenz groups, 83 percent and 80 percent of subjects, respectively, had undetectable amounts of HIV in their blood after 48 weeks of treatment. Patients receiving Edurant who had a higher viral load at the start of therapy were more likely not to respond to the drug than were patients with a lower viral load at the start of therapy. In addition, persons who failed therapy with Edurant developed more drug resistance than patients who failed efavirenz.
The most commonly reported side effects in patients taking Edurant included depression, difficulty sleeping (insomnia), headache and rash. Fewer patients stopped taking the drug due to side effects as compared to patients taking efavirenz.
Edurant does not cure HIV infection. Patients must stay on continuous HIV therapy to control HIV infection and decrease HIV-related illnesses.
Edurant is manufactured by Raritan, N.J.-based Tibotec Therapeutics, a division of Centocor Ortho Biotech Inc.
For more information:
FDA: HIV and AIDS Activities
http://www.fda.gov/ForConsumers/byAudience/ForPatientAdvocates/HIVandAIDSActivities/default.htm
FDA: Antiretroviral drugs used in the treatment of HIV infection
http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm118915.htm
CDC: HIV/AIDS
http://www.cdc.gov/hiv/default.htm
HHS: AIDS News and Resources
http://www.aids.gov/
AIDS Information
http://www.aidsinfo.nih.gov/
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation's food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
Media Inquiries:Erica Jefferson, 301-796-4988, erica.jefferson@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA
SOURCE U.S. Food and Drug Administration
Medivir Announces Positive 48-week Interim Data from TMC435 Hepatitis C Phase 2b ASPIRE Study in Treatment-Experienced Genotype-1 Patients...
I need to add 'SVR4' to my list of HCV Direct Acting Antiviral terminology... 'SVR4' is SVR 4 weeks post end of treatment date. Glad to get that squared away. This press release covers the majority of results of the phase IIb trial (ASPIRE) with the HCV protease inhibitor TMC435 looking at those who were previous non-responders to previous Peg-inf + P/R therapy - Relapsers, Partial Responders and Null-Responders to be specific. SVR4 in the TMC435 150mg + P/R was achieved in 88%, 77% and 57% oof those respective populations vs 50%, 11% and 23% in the placebo + P/R ar, again, respectively. No relevant differences between the 12, 24 and 48 week arms. Serious AEs were reported in 6.1% subjects in the placebo and vs 8.3% of the subjects treated with TMC435 with no substantial differences seen between the TMC435 dose groups. AEs leading to treatment discontinuation were reported in 4.5% of the placebo subjects and in 8.8% of the TMC435 treated subjects. The relative lack of AE's compared to the first generation of HCV PIs and the once a day dosing make TMC435 one to keep our eyes on.
HUDDINGE, Sweden, May 20, 2011 /PRNewswire/ --
- All TMC435 Patient Subgroups Achieved Substantially Higher SVR4 Rates (Undetectable Virus 4 Weeks After End of Treatment) Compared to pegylated-interferon and ribavirin Alone
- TMC435 was Safe and Well Tolerated at All Doses and Treatment Durations
Medivir AB (OMX: MVIR), the emerging research-based specialty
pharmaceutical company focused on infectious diseases, today announced results from the ASPIRE phase 2b study that evaluates the addition of once daily TMC435 to pegylated interferon and ribavirin in patients with genotype 1 chronic hepatitis C whose prior treatment with pegylated-interferon (PegIFN) and ribavirin (RBV) was unsuccessful either because they relapsed, had a partial response or had a null response.
Bertil Samuelsson, CSO of Medivir, commented, "We are delighted with the encouraging efficacy and safety results shown by TMC435-based triple therapy over pegylated-interferon and ribavirin, in this 48-Week interim analysis of the ASPIRE study in treatment experienced genotype-1 hepatitis C patients. This patient group is known to be the most difficult one to treat, where in particular prior null and partial responder groups respond very poorly upon retreatment with PegIFN/RBV alone. With several global phase 3 clinical trials ongoing in hepatitis C patients we are expecting the momentum to continue with regards to the development of TMC435."
ASPIRE (C206) - Design and Week-48 Interim Analysis
TMC435, a potent, once-daily, oral hepatitis C virus protease inhibitor is being developed by Tibotec jointly with Medivir. The randomized, placebo-controlled, double-blind ASPIRE study evaluates the effect of TMC435 in combination with pegylated-interferon and ribavirin in 462 patients infected with genotype-1 hepatitis C virus who have failed prior treatment with PegIFN/RBV. The study includes patients that have relapsed, achieved partial response, or achieved no response (null responders) to SoC treatment and where 62 percent (287/462) of patients overall had advanced liver disease, periportal or septal fibrosis or cirrhosis (scarring of the liver) upon study entry (Metavir score F2-F4).
Patients were equally randomized to 1 of 7 different treatment arms: 6 TMC435 treatment arms and one placebo arm. TMC435 was administered once daily at a dose of either 100 mg or 150 mg given for either 12, 24, or 48 weeks in combination with PegIFN/RBV. PegIFN/RBV treatment was continued in all patients until the study completion at week 48. This interim analysis was performed when all patients had completed 48 weeks of treatment or discontinued earlier. The analysis was done based on the intent-to-treat, ITT, population which included all randomized subjects who took at least one dose of the study medication. SVR4, Sustained Virologic Response 4 weeks after planned end of treatment data, was available for 94% and 84% of TMC435 and placebo patients respectively.
ASPIRE Results - Efficacy
In this Week 48 interim analysis, all subgroups of treatment-experienced patients who failed previous peginterferon and ribavirin treatment, achieved substantially higher virologic response rates following treatment with TMC435-containing regimen at all doses and durations, compared with pegylated-interferon and ribavirin.
There was no relevant difference in virological response between the TMC435 150 mg dose groups who received TMC435-based triple therapy of 12 weeks, 24 weeks or 48 weeks. At end of treatment (EoT) 92%, 83% and 71% of relapser patients, partial responder patients and null responder patients taking TMC435 150 mg once daily and placebo, respectively, achieved undetectable HCV RNA levels compared to 70%, 17% and 25% in the placebo PegIFN/RBV groups respectively. At week 4 after cessation of treatment (SVR4) 88%, 77% and 57% of prior relapser patients, partial responder patients and null responder patients taking TMC435 150 mg once daily and placebo, respectively, achieved undetectable HCV RNA levels, compared to 50%, 11% and 23% in the placebo groups, respectively.
Virological Response Rates in TMC435 Dose Groups (150 mg q.d.) vs
Placebo
TMC435 TMC435 TMC435 All TMC435 Placebo
% (n/N) 12PR48 24PR48 48PR48 PR48 PR48
N=66 N=68 N=65 N=199 N=66
Prior EoT 92 (24/26) 93 (25/27) 92 (24/26) 92 (73/79) 70 (19/27)
Relapser
SVR4 84 (21/25) 93 (25/27) 85 (22/26) 87 (68/78) 50 (12/24)
Prior EoT 78 (18/23) 83 (20/24) 86 (19/22) 83 (57/69) 17 (4/23)
Partial
Responder SVR4 64 (14/22) 86 (18/21) 82 (18/22) 77 (50/65) 11 (2/18)
Prior Null EoT 65 (11/17) 71 (12/17) 77 (13/17) 71 (36/51) 25 (4/16)
Responder
SVR4 56 (9/16) 60 (9/15) 56 (9/16) 57 (27/47) 23 (3/13)
q.d.: once daily; PR: pegIFNalpha-2A and ribavirin; EoT: End of Treatment,
SVR4: patients with undetectable HCV RNA (<25 IU/mL Undetectable) at EOT and 4 weeks after planned EoT. Prior Relapser: undetectable HCV RNA at EoT and detectable within 24 weeks of follow-up
Partial Responders: more than 2 log reduction in HCV RNA at W12 but not achieving undetectable at EoT
Prior Null Responders: less than 2 log reduction in HCV RNA at W12
Results - Safety and Tolerability
TMC435 was generally safe and well tolerated and overall incidence of adverse events (AEs) was similar across treatment groups. Most of the AEs were grade 1 or 2 in severity. Serious AEs (SAEs) were reported in 6.1% subjects in the placebo and in 8.3% of the subjects treated with TMC435 with no substantial differences seen between the TMC435 dose groups. AEs leading to treatment discontinuation were reported in 4.5% of the placebo subjects and in 8.8% of the TMC435 treated subjects. Patients in the TMC435 ASPIRE treatment groups had overall longer treatment duration than patients in the placebo group due to a higher frequency of early discontinuation in the placebo group caused by treatment failures (i.e. reaching viral stopping rules). The most common AEs during the treatment period were headache, fatigue, pruritus and influenza-like illness.
Incidence was similar across treatment groups and the level of AEs and frequency were consistent with prior phase 2b PILLAR study of TMC435.
In the safety analyses, special attention was given to the following AEs of interest: hepatobiliary AEs, pruritus, rash, anemia and cardiac events. Most AEs of interest were grade 1 or 2 in severity and infrequently led to treatment discontinuation. For each category of AEs of interest the incidence was similar with TMC435 and PegIFN/RBV.
Mild and reversible increases in bilirubin (total, direct and indirect) were observed in TMC435 dose groups with no differences between 100 mg and 150 mg. There were no meaningful differences between treatment groups for any of the other laboratory parameters. There were no clinically significant findings on vital signs, nor were there any relevant changes in electrocardiogram (ECG) parameters, including QTc. Mean alanine aminotransferase (ALT) levels decreased in all treatment groups.
About TMC435 in other clinical studies
TMC435 is a once-daily (q.d.) protease inhibitor drug jointly developed by Tibotec Pharmaceuticals and, to treat chronic hepatitis C virus infections.
Three global clinical phase 3 response guided studies were recently initiated by Tibotec:
- TMC435-C208 or QUEST-1 includes approximately 375 treatment-naive patients
- TMC435-C216 or QUEST-2 includes approximately 375 treatment-naive patients
- TMC435-C3007 or PROMISE includes approximately 375 who have relapsed after prior interferon-based treatment
In parallel to the recent start of the global phase 3-studies, TMC435 is currently in a follow up phase in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naive and in G1 patients that failed previous IFN-based treatment. More safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2011. Phase 3 programs for TMC435 are also ongoing in Japan.
For additional information for these studies, please see http://www.clinicaltrials.gov
Conference call for analysts and investors:
There will be a conference call today, May 20 2011, for investors and analysts at 08.00 (EDT) / 13.00 (GMT) / 14.00 (CET) to discuss the data. To dial-in to the conference call please use the following numbers:
Participant Telephone Numbers: +1-718-354-1359 USA
+46(0)8-5051-3785 Sweden
+44(0)20-7136-2053 UK
Participant code 1156834
Soundbyte Replay Access Number: +44(0)20-7111-1244 UK
+1-347-366-9565 USA
+46(0)8-5051-3897 Sweden
Replay Access Code: 1156834#
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.
About Medivir
Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company's key pipeline asset is TMC435, a protease inhibitor which has recently entered phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals.
Medivir is also marketing its first product, the unique cold sore product Xerese(TM)/Xerclear(R) which has recently been launched on the US market. Xerese(TM)/Xerclear(R), which is also approved in Europe, is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia and with Meda AB in North America, Canada and Mexico. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.
For more information about Medivir, please visit the Company's website: http://www.medivir.com.
For more information about Medivir, please contact:
Medivir (http://www.medivir.com):
Rein Piir, CFO & VP Investor Relations Mobile: +46-708-537-292
Bertil Samuelsson, CSO Research & Development +46-8-54683100
M:Communications:
Mary-Jane Elliott / Amber Bielecka / Katja Toon +44(0)20-7920-2330
Medivir@mcomgroup.com
USA: Roland Tomforde +1-212-232-2356
SOURCE Medivir AB
HUDDINGE, Sweden, May 20, 2011 /PRNewswire/ --
- All TMC435 Patient Subgroups Achieved Substantially Higher SVR4 Rates (Undetectable Virus 4 Weeks After End of Treatment) Compared to pegylated-interferon and ribavirin Alone
- TMC435 was Safe and Well Tolerated at All Doses and Treatment Durations
Medivir AB (OMX: MVIR), the emerging research-based specialty
pharmaceutical company focused on infectious diseases, today announced results from the ASPIRE phase 2b study that evaluates the addition of once daily TMC435 to pegylated interferon and ribavirin in patients with genotype 1 chronic hepatitis C whose prior treatment with pegylated-interferon (PegIFN) and ribavirin (RBV) was unsuccessful either because they relapsed, had a partial response or had a null response.
Bertil Samuelsson, CSO of Medivir, commented, "We are delighted with the encouraging efficacy and safety results shown by TMC435-based triple therapy over pegylated-interferon and ribavirin, in this 48-Week interim analysis of the ASPIRE study in treatment experienced genotype-1 hepatitis C patients. This patient group is known to be the most difficult one to treat, where in particular prior null and partial responder groups respond very poorly upon retreatment with PegIFN/RBV alone. With several global phase 3 clinical trials ongoing in hepatitis C patients we are expecting the momentum to continue with regards to the development of TMC435."
ASPIRE (C206) - Design and Week-48 Interim Analysis
TMC435, a potent, once-daily, oral hepatitis C virus protease inhibitor is being developed by Tibotec jointly with Medivir. The randomized, placebo-controlled, double-blind ASPIRE study evaluates the effect of TMC435 in combination with pegylated-interferon and ribavirin in 462 patients infected with genotype-1 hepatitis C virus who have failed prior treatment with PegIFN/RBV. The study includes patients that have relapsed, achieved partial response, or achieved no response (null responders) to SoC treatment and where 62 percent (287/462) of patients overall had advanced liver disease, periportal or septal fibrosis or cirrhosis (scarring of the liver) upon study entry (Metavir score F2-F4).
Patients were equally randomized to 1 of 7 different treatment arms: 6 TMC435 treatment arms and one placebo arm. TMC435 was administered once daily at a dose of either 100 mg or 150 mg given for either 12, 24, or 48 weeks in combination with PegIFN/RBV. PegIFN/RBV treatment was continued in all patients until the study completion at week 48. This interim analysis was performed when all patients had completed 48 weeks of treatment or discontinued earlier. The analysis was done based on the intent-to-treat, ITT, population which included all randomized subjects who took at least one dose of the study medication. SVR4, Sustained Virologic Response 4 weeks after planned end of treatment data, was available for 94% and 84% of TMC435 and placebo patients respectively.
ASPIRE Results - Efficacy
In this Week 48 interim analysis, all subgroups of treatment-experienced patients who failed previous peginterferon and ribavirin treatment, achieved substantially higher virologic response rates following treatment with TMC435-containing regimen at all doses and durations, compared with pegylated-interferon and ribavirin.
There was no relevant difference in virological response between the TMC435 150 mg dose groups who received TMC435-based triple therapy of 12 weeks, 24 weeks or 48 weeks. At end of treatment (EoT) 92%, 83% and 71% of relapser patients, partial responder patients and null responder patients taking TMC435 150 mg once daily and placebo, respectively, achieved undetectable HCV RNA levels compared to 70%, 17% and 25% in the placebo PegIFN/RBV groups respectively. At week 4 after cessation of treatment (SVR4) 88%, 77% and 57% of prior relapser patients, partial responder patients and null responder patients taking TMC435 150 mg once daily and placebo, respectively, achieved undetectable HCV RNA levels, compared to 50%, 11% and 23% in the placebo groups, respectively.
Virological Response Rates in TMC435 Dose Groups (150 mg q.d.) vs
Placebo
TMC435 TMC435 TMC435 All TMC435 Placebo
% (n/N) 12PR48 24PR48 48PR48 PR48 PR48
N=66 N=68 N=65 N=199 N=66
Prior EoT 92 (24/26) 93 (25/27) 92 (24/26) 92 (73/79) 70 (19/27)
Relapser
SVR4 84 (21/25) 93 (25/27) 85 (22/26) 87 (68/78) 50 (12/24)
Prior EoT 78 (18/23) 83 (20/24) 86 (19/22) 83 (57/69) 17 (4/23)
Partial
Responder SVR4 64 (14/22) 86 (18/21) 82 (18/22) 77 (50/65) 11 (2/18)
Prior Null EoT 65 (11/17) 71 (12/17) 77 (13/17) 71 (36/51) 25 (4/16)
Responder
SVR4 56 (9/16) 60 (9/15) 56 (9/16) 57 (27/47) 23 (3/13)
q.d.: once daily; PR: pegIFNalpha-2A and ribavirin; EoT: End of Treatment,
SVR4: patients with undetectable HCV RNA (<25 IU/mL Undetectable) at EOT and 4 weeks after planned EoT. Prior Relapser: undetectable HCV RNA at EoT and detectable within 24 weeks of follow-up
Partial Responders: more than 2 log reduction in HCV RNA at W12 but not achieving undetectable at EoT
Prior Null Responders: less than 2 log reduction in HCV RNA at W12
Results - Safety and Tolerability
TMC435 was generally safe and well tolerated and overall incidence of adverse events (AEs) was similar across treatment groups. Most of the AEs were grade 1 or 2 in severity. Serious AEs (SAEs) were reported in 6.1% subjects in the placebo and in 8.3% of the subjects treated with TMC435 with no substantial differences seen between the TMC435 dose groups. AEs leading to treatment discontinuation were reported in 4.5% of the placebo subjects and in 8.8% of the TMC435 treated subjects. Patients in the TMC435 ASPIRE treatment groups had overall longer treatment duration than patients in the placebo group due to a higher frequency of early discontinuation in the placebo group caused by treatment failures (i.e. reaching viral stopping rules). The most common AEs during the treatment period were headache, fatigue, pruritus and influenza-like illness.
Incidence was similar across treatment groups and the level of AEs and frequency were consistent with prior phase 2b PILLAR study of TMC435.
In the safety analyses, special attention was given to the following AEs of interest: hepatobiliary AEs, pruritus, rash, anemia and cardiac events. Most AEs of interest were grade 1 or 2 in severity and infrequently led to treatment discontinuation. For each category of AEs of interest the incidence was similar with TMC435 and PegIFN/RBV.
Mild and reversible increases in bilirubin (total, direct and indirect) were observed in TMC435 dose groups with no differences between 100 mg and 150 mg. There were no meaningful differences between treatment groups for any of the other laboratory parameters. There were no clinically significant findings on vital signs, nor were there any relevant changes in electrocardiogram (ECG) parameters, including QTc. Mean alanine aminotransferase (ALT) levels decreased in all treatment groups.
About TMC435 in other clinical studies
TMC435 is a once-daily (q.d.) protease inhibitor drug jointly developed by Tibotec Pharmaceuticals and, to treat chronic hepatitis C virus infections.
Three global clinical phase 3 response guided studies were recently initiated by Tibotec:
- TMC435-C208 or QUEST-1 includes approximately 375 treatment-naive patients
- TMC435-C216 or QUEST-2 includes approximately 375 treatment-naive patients
- TMC435-C3007 or PROMISE includes approximately 375 who have relapsed after prior interferon-based treatment
In parallel to the recent start of the global phase 3-studies, TMC435 is currently in a follow up phase in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naive and in G1 patients that failed previous IFN-based treatment. More safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2011. Phase 3 programs for TMC435 are also ongoing in Japan.
For additional information for these studies, please see http://www.clinicaltrials.gov
Conference call for analysts and investors:
There will be a conference call today, May 20 2011, for investors and analysts at 08.00 (EDT) / 13.00 (GMT) / 14.00 (CET) to discuss the data. To dial-in to the conference call please use the following numbers:
Participant Telephone Numbers: +1-718-354-1359 USA
+46(0)8-5051-3785 Sweden
+44(0)20-7136-2053 UK
Participant code 1156834
Soundbyte Replay Access Number: +44(0)20-7111-1244 UK
+1-347-366-9565 USA
+46(0)8-5051-3897 Sweden
Replay Access Code: 1156834#
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.
About Medivir
Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company's key pipeline asset is TMC435, a protease inhibitor which has recently entered phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals.
Medivir is also marketing its first product, the unique cold sore product Xerese(TM)/Xerclear(R) which has recently been launched on the US market. Xerese(TM)/Xerclear(R), which is also approved in Europe, is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia and with Meda AB in North America, Canada and Mexico. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.
For more information about Medivir, please visit the Company's website: http://www.medivir.com.
For more information about Medivir, please contact:
Medivir (http://www.medivir.com):
Rein Piir, CFO & VP Investor Relations Mobile: +46-708-537-292
Bertil Samuelsson, CSO Research & Development +46-8-54683100
M:Communications:
Mary-Jane Elliott / Amber Bielecka / Katja Toon +44(0)20-7920-2330
Medivir@mcomgroup.com
USA: Roland Tomforde +1-212-232-2356
SOURCE Medivir AB
Tuesday, April 12, 2011
Medivir to buy BioPhausia to "create a platform" for the launch of TMC435....
Medivir to buy BioPhausia for 62 million euros
World News | April 12, 2011
Medivir is to acquire fellow Swedish firm BioPhausia in a deal that will "create a platform" for the launch of its promising hepatitis C treatment.
Under the terms of the deal, Medivir is offering a mixture of cash and new shares, thus valuing BioPhausia at around 565 million Swedish kroner (62 million euros) or 1.65 crowns per share. The offer represents a 44% premium over the average price of BioPhausia shares over the last 30 days and the latter's board has unanimously recommended the offer.
The Huddinge-headquartered group says that BioPhausia will provide it with "complementary competencies in regulatory affairs, logistics, distribution, marketing, sales and quality assurance", plus a local presence in Sweden, Denmark and Finland. It also brings quite healthy revenues; turnover in 2010 came in at 506 million kroner, compared to Medivir's 62 million kroner.
Seeking sustainable profits
Ron Long, Medivir's chief executive, said the acquisition brings the firm closer to "achieving its goal of becoming a sustainably profitable, research-based specialty pharmaceutical company". He added that the BioPhausia team will "significantly advance our commercial capabilities as we prepare to realize full value from TMC435".
The latter is a once-daily, protease inhibitor for hepatitis C, which is partnered with Johnson & Johnson affiliate Tibotec and has recently reported positive interim data in three Phase IIb studies. It has moved to Phase III and Medivir has retained full commercial rights to TMC435 in the Nordic region.
Links
www.medivir.se
www.biophausia.se
World News | April 12, 2011
Medivir is to acquire fellow Swedish firm BioPhausia in a deal that will "create a platform" for the launch of its promising hepatitis C treatment.
Under the terms of the deal, Medivir is offering a mixture of cash and new shares, thus valuing BioPhausia at around 565 million Swedish kroner (62 million euros) or 1.65 crowns per share. The offer represents a 44% premium over the average price of BioPhausia shares over the last 30 days and the latter's board has unanimously recommended the offer.
The Huddinge-headquartered group says that BioPhausia will provide it with "complementary competencies in regulatory affairs, logistics, distribution, marketing, sales and quality assurance", plus a local presence in Sweden, Denmark and Finland. It also brings quite healthy revenues; turnover in 2010 came in at 506 million kroner, compared to Medivir's 62 million kroner.
Seeking sustainable profits
Ron Long, Medivir's chief executive, said the acquisition brings the firm closer to "achieving its goal of becoming a sustainably profitable, research-based specialty pharmaceutical company". He added that the BioPhausia team will "significantly advance our commercial capabilities as we prepare to realize full value from TMC435".
The latter is a once-daily, protease inhibitor for hepatitis C, which is partnered with Johnson & Johnson affiliate Tibotec and has recently reported positive interim data in three Phase IIb studies. It has moved to Phase III and Medivir has retained full commercial rights to TMC435 in the Nordic region.
Links
www.medivir.se
www.biophausia.se
Friday, April 1, 2011
Medivr/Tibotec QD HCV PI TMC435 Interim 24 week data from Phase 2b ASPIRE trial presented at EASL...
This is by far the cockiest press release I've read thus far that's associated with EASL, and I've had an eyeful. But the Medivir/Tibotec partnership has good reason to be at least somewhat arrogant. If they can keep these numbers looking as good 6 months post-treatment, then TMC435 will be the next gen DAA poised to usurp what looks to be Telaprevir’s throne. TMC435 looks to have extraordinary efficacy and tolerability in combination with PEG and Ribavirin at 24 weeks, boasting as much as 93.3% week 24 HCV RNA < 25 IU/mL in prior NULL responders in the 48 weeks TMC435 + Peg + RBV for 48 weeks arm (yes, NULL responders!) . Take a look at the tables here: http://www.prnewswire.com/news-releases/medivir-week-24-interim-results-from-tmc435-hepatitis-c-phase-2b-aspire-study-presented-at-easl-119040924.html
HUDDINGE, Sweden, April 1, 2011 /PRNewswire-FirstCall/ --
- Results Show Potent Antiviral Efficacy of Once Daily 150 mg TMC435 in Hepatitis C Patients Who Have Failed Earlier Treatment, Especially in Prior Null Responders, and Excellent Safety and Tolerability
Medivir AB (OMX: MVIR), the emerging research-based specialty pharmaceutical company focused on infectious diseases, announces that their partner, Tibotec has presented the results of a planned Week 24 interim analysis of the phase 2b ASPIRE study for TMC435 in treatment experienced hepatitis C patients in a late-breaker session at the 46th Annual meeting of the European Association for the Study of the Liver (EASL), Berlin, Germany.
Treatment experienced patients are known to be the most difficult to treat hepatitis C patient group.
TMC435 is a potent, once-daily, oral hepatitis C virus protease inhibitor which recently entered clinical phase 3 studies. The study enrolled patients chronically infected with genotype-1 hepatitis C virus (HCV) that had previously failed treatment with standard of care therapy (peginterferon and ribavarin). TMC435 is being jointly developed by Medivir and its partner Tibotec.
In this Week 24 interim analysis, treatment-experienced patients who failed peginterferon and ribavarin treatment achieved significantly greater virologic response rates following treatment with TMC435-containing regimen at all doses, compared with placebo. Results demonstrated that the TMC435 150 mg dose group showed the highest response, particularly in prior null responders. In this 150 mg dose group, HCV RNA levels were undetectable at week 24 for between 82% and 91% of the patients. Results also showed that there was no statistically relevant difference in safety and tolerability between the TMC435 and placebo treated groups.
Ron Long, CEO of Medivir, commented: "We are delighted that these strong results are to be presented at such a prestigious scientific conference as EASL. TMC435 continues to demonstrate why Medivir are so confident that hepatitis C treatment can be significantly changed by a more convenient, once daily protease inhibitor especially for treatment experienced patients. These data and the recent start of phase 3 clinical studies for TMC435, represent an exciting stage in Medivir's development as a significant player in the infectious disease market."
The ASPIRE study evaluates the effect of TMC435 in combination with standard of care (SoC) in 462 patients infected with the difficult to treat genotype-1 hepatitis C virus who had undergone and failed prior treatment with (SoC). The study includes patients that have relapsed, achieved partial response, or achieved no response (null responders) to treatment with standard of care. TMC435 was administered once daily at a dose of either 100 mg or 150mg given for either 12, 24, or 48 weeks in combination with standard of care. Standard of care treatment was continued until the study completion at week 48.
As well as the late-breaker ASPIRE data presented, a further three presentations will be made at EASL on TMC435. These include:
Oral presentation: Impact of IL28b genotype and pretreatment serum IP-10 in treatment-naive genotype-1 HCV patients treated with TMC435 in combination with peginterferona-2a and ribavirin in PILLAR study, J. Aerssens, which found that during 24 weeks of treatment, IL28B genotype and serum IP-10 were predictive of response in patients receiving standard of care (peginterferon and ribavirin) but had limited predictive value in patients treated with both TMC435 and peginterferon and ribavirin, therefore suggesting that TMC435, a potent, once daily oral protease inhibitor, may overcome the negative consequences of unfavourable host genotype encountered with pegIFN/RBV.
Poster presentation No.472: Pharmacokinetics of TMC435 in subjects with moderate hepatic impairment, V. Sekar, which found that no TMC435 dose adjustment was necessary for patients with moderate liver impairment.
Poster presentation No.1221: Treatment outcome and resistance analysis in HCV genotype 1 patients previously exposed to TMC435 monotherapy and re-treated with TMC435 in combination with pegifna-2a/ribavirin, O. Lenz, which found that viral variants in patients who had received TMC435 as a monotherapy were no longer detected over time and successful treatment after prior exposure to TMC435 with emergence of resistance variants was possible in 3/5 patients who had failed interferon-based therapy.
About TMC435 in other clinical studies
TMC435 is a once-daily (q.d.) protease inhibitor drug jointly developed by Medivir and Tibotec Pharmaceuticals, to treat chronic hepatitis C virus infections.
Three clinical phase 3 response guided studies were recently initiated:
- TMC435-C208 or QUEST-1 includes approximately 375 treatment-naive patients
- TMC435-C216 or QUEST-2 includes approximately 375 treatment-naive patients
- TMC435-C3007 or PROMISE includes approximately 375 who have relapsed after prior interferon-based treatment
In parallel to the recent start of the global phase 3-studies, TMC435 is currently in a follow up phase in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naive and in G1 patients that failed previous IFN-based treatment. More safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2011.
A phase 3 program for TMC435 has also recently been launched in Japan.
For additional information for these studies, please see http://www.clinicaltrials.gov
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.
About Medivir
Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company's key pipeline asset is TMC435, a protease inhibitor which has recently entered phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals.
Medivir is also marketing its first product, the unique cold sore product Xerese(TM)/Xerclear(R) which has recently been launched on the US market. Xerese(TM)/Xerclear(R), which is also approved in Europe, is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia and with Meda AB in North America, Canada and Mexico. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.
For more information about Medivir, please visit the Company's website: http://www.medivir.com.
For more information about Medivir, please contact:
Medivir (http://www.medivir.com):
Rein Piir, CFO & VP Investor Relations
Mobile: +46-708-537-292
Bertil Samuelsson, CFO Mobile: +46(70)576-13-50
M:Communications:
Mary-Jane Elliott / Amber Bielecka / Katja Toon
Medivir@mcomgroup.com
+44(0)20-7920 2330
USA: Roland Tomforde
+1-212-232-2356
Read the full press release with tables
HUDDINGE, Sweden, April 1, 2011 /PRNewswire-FirstCall/ --
- Results Show Potent Antiviral Efficacy of Once Daily 150 mg TMC435 in Hepatitis C Patients Who Have Failed Earlier Treatment, Especially in Prior Null Responders, and Excellent Safety and Tolerability
Medivir AB (OMX: MVIR), the emerging research-based specialty pharmaceutical company focused on infectious diseases, announces that their partner, Tibotec has presented the results of a planned Week 24 interim analysis of the phase 2b ASPIRE study for TMC435 in treatment experienced hepatitis C patients in a late-breaker session at the 46th Annual meeting of the European Association for the Study of the Liver (EASL), Berlin, Germany.
Treatment experienced patients are known to be the most difficult to treat hepatitis C patient group.
TMC435 is a potent, once-daily, oral hepatitis C virus protease inhibitor which recently entered clinical phase 3 studies. The study enrolled patients chronically infected with genotype-1 hepatitis C virus (HCV) that had previously failed treatment with standard of care therapy (peginterferon and ribavarin). TMC435 is being jointly developed by Medivir and its partner Tibotec.
In this Week 24 interim analysis, treatment-experienced patients who failed peginterferon and ribavarin treatment achieved significantly greater virologic response rates following treatment with TMC435-containing regimen at all doses, compared with placebo. Results demonstrated that the TMC435 150 mg dose group showed the highest response, particularly in prior null responders. In this 150 mg dose group, HCV RNA levels were undetectable at week 24 for between 82% and 91% of the patients. Results also showed that there was no statistically relevant difference in safety and tolerability between the TMC435 and placebo treated groups.
Ron Long, CEO of Medivir, commented: "We are delighted that these strong results are to be presented at such a prestigious scientific conference as EASL. TMC435 continues to demonstrate why Medivir are so confident that hepatitis C treatment can be significantly changed by a more convenient, once daily protease inhibitor especially for treatment experienced patients. These data and the recent start of phase 3 clinical studies for TMC435, represent an exciting stage in Medivir's development as a significant player in the infectious disease market."
The ASPIRE study evaluates the effect of TMC435 in combination with standard of care (SoC) in 462 patients infected with the difficult to treat genotype-1 hepatitis C virus who had undergone and failed prior treatment with (SoC). The study includes patients that have relapsed, achieved partial response, or achieved no response (null responders) to treatment with standard of care. TMC435 was administered once daily at a dose of either 100 mg or 150mg given for either 12, 24, or 48 weeks in combination with standard of care. Standard of care treatment was continued until the study completion at week 48.
As well as the late-breaker ASPIRE data presented, a further three presentations will be made at EASL on TMC435. These include:
Oral presentation: Impact of IL28b genotype and pretreatment serum IP-10 in treatment-naive genotype-1 HCV patients treated with TMC435 in combination with peginterferona-2a and ribavirin in PILLAR study, J. Aerssens, which found that during 24 weeks of treatment, IL28B genotype and serum IP-10 were predictive of response in patients receiving standard of care (peginterferon and ribavirin) but had limited predictive value in patients treated with both TMC435 and peginterferon and ribavirin, therefore suggesting that TMC435, a potent, once daily oral protease inhibitor, may overcome the negative consequences of unfavourable host genotype encountered with pegIFN/RBV.
Poster presentation No.472: Pharmacokinetics of TMC435 in subjects with moderate hepatic impairment, V. Sekar, which found that no TMC435 dose adjustment was necessary for patients with moderate liver impairment.
Poster presentation No.1221: Treatment outcome and resistance analysis in HCV genotype 1 patients previously exposed to TMC435 monotherapy and re-treated with TMC435 in combination with pegifna-2a/ribavirin, O. Lenz, which found that viral variants in patients who had received TMC435 as a monotherapy were no longer detected over time and successful treatment after prior exposure to TMC435 with emergence of resistance variants was possible in 3/5 patients who had failed interferon-based therapy.
About TMC435 in other clinical studies
TMC435 is a once-daily (q.d.) protease inhibitor drug jointly developed by Medivir and Tibotec Pharmaceuticals, to treat chronic hepatitis C virus infections.
Three clinical phase 3 response guided studies were recently initiated:
- TMC435-C208 or QUEST-1 includes approximately 375 treatment-naive patients
- TMC435-C216 or QUEST-2 includes approximately 375 treatment-naive patients
- TMC435-C3007 or PROMISE includes approximately 375 who have relapsed after prior interferon-based treatment
In parallel to the recent start of the global phase 3-studies, TMC435 is currently in a follow up phase in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naive and in G1 patients that failed previous IFN-based treatment. More safety and efficacy data from the phase 2b trials will be presented at scientific meetings later in 2011.
A phase 3 program for TMC435 has also recently been launched in Japan.
For additional information for these studies, please see http://www.clinicaltrials.gov
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.
About Medivir
Medivir is an emerging research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company's key pipeline asset is TMC435, a protease inhibitor which has recently entered phase 3 clinical development for hepatitis C and is partnered with Tibotec Pharmaceuticals.
Medivir is also marketing its first product, the unique cold sore product Xerese(TM)/Xerclear(R) which has recently been launched on the US market. Xerese(TM)/Xerclear(R), which is also approved in Europe, is partnered with GlaxoSmithKline to be sold OTC in Europe, Japan and Russia and with Meda AB in North America, Canada and Mexico. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.
For more information about Medivir, please visit the Company's website: http://www.medivir.com.
For more information about Medivir, please contact:
Medivir (http://www.medivir.com):
Rein Piir, CFO & VP Investor Relations
Mobile: +46-708-537-292
Bertil Samuelsson, CFO Mobile: +46(70)576-13-50
M:Communications:
Mary-Jane Elliott / Amber Bielecka / Katja Toon
Medivir@mcomgroup.com
+44(0)20-7920 2330
USA: Roland Tomforde
+1-212-232-2356
Read the full press release with tables
Monday, December 20, 2010
Janssen Seeks European Marketing Authorization For Investigational Hepatitis C Treatment Telaprevir
It will be interesting to see how Tibotec supports Telaprevir in Europe, with a possible competitor, TMC435 waiting in the wings. Vertex, with it's relatively rich, advanced pipeline in HCV, esp with the relatively drug-interaction free HCV non-nuc VX-222 that would be a nice complementary acquisition for the J&J family. According to outside sources, Merck only expects a 35% marketshare for Boceprevir vs Telaprevir. Given the potential baggage that comes along with Telaprevir with Q8h dosing, highly variable PK at q12h and the potential severity of the rash, esp in people of color, Merck (for once) may be underestimating the market potential of Boceprevir - Chris
Janssen-Cilag International NV announced the submission of a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) for telaprevir, an investigational, oral, direct-acting antiviral for the treatment of chronic genotype 1 hepatitis C virus (HCV), the most common form of the virus. Telaprevir is a potent and selective protease inhibitor (PI), which when combined with pegylated-interferon and ribavirin (the current treatment standard), shows activity in patients that are new to treatment and who have been previously treated but were not cured, including partial responders, relapsers and those who have had little or no response (null responders) to the current standard of treatment.
The EMA has accepted telaprevir for accelerated assessment, which is granted to quicken access to innovative, new medicines of major public-health interest. Tibotec BVBA, a global research and development company with specific experience in virology, is developing telaprevir in collaboration with Vertex Pharmaceuticals. Tibotec BVBA is an affiliate company of Janssen.
"The EMA submission for telaprevir is a landmark in the treatment of HCV and demonstrates our dedication to addressing unmet medical needs by developing innovative treatments for infectious diseases," said Johan Van Hoof, Global Therapeutic Area Head Infectious Diseases and Vaccines at Janssen. "Above all, it is an important step towards making telaprevir available to people living with HCV."
It is estimated that 170 million people are living with HCV around the world, including more than five million in Europe. Chronic HCV can result in serious long-term health problems, and an estimated 30 percent of patients will develop progressive liver disease, including cirrhosis (damage and scarring of the liver), which places them at risk for liver insufficiency and liver cancer. HCV is the most common cause of liver transplant in Europe.
The current standard of care for HCV genotype 1 patients, pegylated-interferon and ribavirin, is administered for 48 weeks and only 40 to 50 percent of genotype 1 patients achieve a sustained virologic response (SVR), defined as achieving undetectable levels of the virus in the blood for six months after completion of treatment, and considered an indicator of cure. Re-treatment with pegylated-interferon and ribavirin in patients who have previously failed this treatment shows only limited success. ,
The EMA submission is supported by results from three phase 3 studies, which compared telaprevir in combination with the current standard of treatment to the current standard of treatment alone in HCV genotype 1 patients. Results were very positive:
- Significantly higher SVR rates were observed in treatment-naïve patients treated with telaprevir compared to the current standard treatment of pegylated-interferon and ribavirin (75 percent vs. 44 percent)
- The majority of patients were cured by week 24, which is half the duration of therapy with the current standard of treatment8,
- There was a three-fold increase in cure rates (65 percent vs. 17 percent) across all types of previously treated patients who were given telaprevir compared to the current treatment standard, including prior null responders (31 percent vs. 5 percent) 10
- The most common adverse events in the telaprevir-based treatment groups were fatigue, pruritus, nausea, headache, anemia, rash, influenza-like illness, insomnia, fever and diarrhea. The majority of these adverse events were mild to moderate.8,9,10
"Current treatment for hepatitis is lengthy and only effective for approximately half of treatment-naïve patients, and even fewer patients who failed previous treatment," commented Stefan Zeuzem, Professor of Medicine and Chief, department of medicine, J W Goethe University Hospital, Frankfurt. "If approved, telaprevir would help to significantly improve cure rates and shorten treatment duration for many people living with HCV, compared to current standard treatment."
About the Telaprevir Development Program
To date, more than 2,500 people with HCV genotype 1 have received telaprevir-based therapy (telaprevir combined with the current standard of treatment) as part of Phase 2 studies and the Phase 3 ADVANCE, ILLUMINATE and REALIZE trials.8,9,10 The telaprevir clinical development program is the largest conducted to date for any investigational direct-acting antiviral hepatitis C therapy.
- ADVANCE evaluated telaprevir-based regimens in approximately 1,088 treatment-naïve patients with chronic HCV infection. Data from the ADVANCE trial were presented at the 2010 American Association for the Study of Liver Diseases (AASLD) annual meeting in November 2010.8
- ILLUMINATE evaluated the benefits of extending telaprevir-based therapy in 540 treatment-naïve patients whose HCV was undetectable at weeks 4 and 12 of treatment. 322 of these patients were randomized to receive 24 or 48 weeks of treatment, and it was found that there was no benefit to extending treatment to 48 weeks. Data from the ILLUMINATE meeting were presented at AASLD in November 2010.9
- REALIZE evaluated telaprevir-based regimens in approximately 650 treatment-failure HCV patients. Data from the REALIZE trial will likely be published in 2011.
Telaprevir is being developed by Tibotec BVBA, an affiliate company of Janssen, in collaboration with Vertex Pharmaceuticals and Mitsubishi Tanabe Pharma for the treatment of genotype 1 HCV in combination with pegylated-interferon and ribavirin in both patients who have failed prior treatment and those who have never been treated. Tibotec BVBA has the commercialisation rights for telaprevir in Europe, Latin America, the Middle East, Africa, India, Australia and New Zealand, pending approval by the respective regulatory authorities. Vertex will commercialise telaprevir in the U.S., Canada and Mexico and Mitsubishi Tanabe Pharma has rights to commercialise telaprevir in Japan and certain Far East countries.
About Tibotec BVBA
Tibotec BVBA is a global pharmaceutical and research development company. The Company's main research and development facilities are in Beerse, Belgium with offices in Titusville, NJ and Cork, Ireland. Tibotec is dedicated to the discovery and development of innovative HIV/AIDS and HCV drugs, and anti-infectives for diseases of high unmet medical need.
Janssen-Cilag International NV announced the submission of a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) for telaprevir, an investigational, oral, direct-acting antiviral for the treatment of chronic genotype 1 hepatitis C virus (HCV), the most common form of the virus. Telaprevir is a potent and selective protease inhibitor (PI), which when combined with pegylated-interferon and ribavirin (the current treatment standard), shows activity in patients that are new to treatment and who have been previously treated but were not cured, including partial responders, relapsers and those who have had little or no response (null responders) to the current standard of treatment.
The EMA has accepted telaprevir for accelerated assessment, which is granted to quicken access to innovative, new medicines of major public-health interest. Tibotec BVBA, a global research and development company with specific experience in virology, is developing telaprevir in collaboration with Vertex Pharmaceuticals. Tibotec BVBA is an affiliate company of Janssen.
"The EMA submission for telaprevir is a landmark in the treatment of HCV and demonstrates our dedication to addressing unmet medical needs by developing innovative treatments for infectious diseases," said Johan Van Hoof, Global Therapeutic Area Head Infectious Diseases and Vaccines at Janssen. "Above all, it is an important step towards making telaprevir available to people living with HCV."
It is estimated that 170 million people are living with HCV around the world, including more than five million in Europe. Chronic HCV can result in serious long-term health problems, and an estimated 30 percent of patients will develop progressive liver disease, including cirrhosis (damage and scarring of the liver), which places them at risk for liver insufficiency and liver cancer. HCV is the most common cause of liver transplant in Europe.
The current standard of care for HCV genotype 1 patients, pegylated-interferon and ribavirin, is administered for 48 weeks and only 40 to 50 percent of genotype 1 patients achieve a sustained virologic response (SVR), defined as achieving undetectable levels of the virus in the blood for six months after completion of treatment, and considered an indicator of cure. Re-treatment with pegylated-interferon and ribavirin in patients who have previously failed this treatment shows only limited success. ,
The EMA submission is supported by results from three phase 3 studies, which compared telaprevir in combination with the current standard of treatment to the current standard of treatment alone in HCV genotype 1 patients. Results were very positive:
- Significantly higher SVR rates were observed in treatment-naïve patients treated with telaprevir compared to the current standard treatment of pegylated-interferon and ribavirin (75 percent vs. 44 percent)
- The majority of patients were cured by week 24, which is half the duration of therapy with the current standard of treatment8,
- There was a three-fold increase in cure rates (65 percent vs. 17 percent) across all types of previously treated patients who were given telaprevir compared to the current treatment standard, including prior null responders (31 percent vs. 5 percent) 10
- The most common adverse events in the telaprevir-based treatment groups were fatigue, pruritus, nausea, headache, anemia, rash, influenza-like illness, insomnia, fever and diarrhea. The majority of these adverse events were mild to moderate.8,9,10
"Current treatment for hepatitis is lengthy and only effective for approximately half of treatment-naïve patients, and even fewer patients who failed previous treatment," commented Stefan Zeuzem, Professor of Medicine and Chief, department of medicine, J W Goethe University Hospital, Frankfurt. "If approved, telaprevir would help to significantly improve cure rates and shorten treatment duration for many people living with HCV, compared to current standard treatment."
About the Telaprevir Development Program
To date, more than 2,500 people with HCV genotype 1 have received telaprevir-based therapy (telaprevir combined with the current standard of treatment) as part of Phase 2 studies and the Phase 3 ADVANCE, ILLUMINATE and REALIZE trials.8,9,10 The telaprevir clinical development program is the largest conducted to date for any investigational direct-acting antiviral hepatitis C therapy.
- ADVANCE evaluated telaprevir-based regimens in approximately 1,088 treatment-naïve patients with chronic HCV infection. Data from the ADVANCE trial were presented at the 2010 American Association for the Study of Liver Diseases (AASLD) annual meeting in November 2010.8
- ILLUMINATE evaluated the benefits of extending telaprevir-based therapy in 540 treatment-naïve patients whose HCV was undetectable at weeks 4 and 12 of treatment. 322 of these patients were randomized to receive 24 or 48 weeks of treatment, and it was found that there was no benefit to extending treatment to 48 weeks. Data from the ILLUMINATE meeting were presented at AASLD in November 2010.9
- REALIZE evaluated telaprevir-based regimens in approximately 650 treatment-failure HCV patients. Data from the REALIZE trial will likely be published in 2011.
Telaprevir is being developed by Tibotec BVBA, an affiliate company of Janssen, in collaboration with Vertex Pharmaceuticals and Mitsubishi Tanabe Pharma for the treatment of genotype 1 HCV in combination with pegylated-interferon and ribavirin in both patients who have failed prior treatment and those who have never been treated. Tibotec BVBA has the commercialisation rights for telaprevir in Europe, Latin America, the Middle East, Africa, India, Australia and New Zealand, pending approval by the respective regulatory authorities. Vertex will commercialise telaprevir in the U.S., Canada and Mexico and Mitsubishi Tanabe Pharma has rights to commercialise telaprevir in Japan and certain Far East countries.
About Tibotec BVBA
Tibotec BVBA is a global pharmaceutical and research development company. The Company's main research and development facilities are in Beerse, Belgium with offices in Titusville, NJ and Cork, Ireland. Tibotec is dedicated to the discovery and development of innovative HIV/AIDS and HCV drugs, and anti-infectives for diseases of high unmet medical need.
Subscribe to:
Comments (Atom)
Posts
