Showing posts with label aasld. Show all posts
Showing posts with label aasld. Show all posts
Tuesday, September 25, 2012
Vertex Pharmaceuticals / Alios BioPharma HCV nuc update...
Posted on 9-25-12 on ClinicaSpace.com. Vertex Pharmaceuticals will continue to develop one nucleotide inhibtior in it's collaboration with Alios BioPharm, ALS-2200 (also known as VX-135), while ending development of ALS-2158 due to lack of efficacy. Vertex is planning on moving ALS-2200 to an all-oral, interferon-free combination Phase II trial in genotype 1 patients later this year.
Vertex Pharmaceuticals Incorporated (VRTX) Ends Work on One Hepatitis C Drug, Continues Another; Stock Down
9/25/2012 7:41:57 AM
CAMBRIDGE, Mass., Sep 25, 2012 (BUSINESS WIRE) -- --- ALS-2200: Data from additional cohort of seven-day viral kinetic study with ALS-2200 (200 mg, QD) in combination with ribavirin show median 4.18 log10 reduction in HCV RNA with 5 of 8 people below the limit of quantification; treatment was well-tolerated -
Vertex Pharmaceuticals Incorporated and its collaborator Alios BioPharma, Inc. today announced results from a viral kinetic study of the adenosine nucleotide analogue pro-drug ALS-2158 for the treatment of hepatitis C. Data showed that seven days of dosing with up to 900 mg of ALS-2158 was well-tolerated in people with genotype 1 chronic hepatitis C, but that there was insufficient antiviral activity to warrant proceeding with further clinical development. The companies also announced new data from an additional cohort of an ongoing viral kinetic study of the uridine nucleotide analogue pro-drug ALS-2200 in combination with ribavirin. There was a median 4.18 log10 reduction from baseline in HCV RNA after seven days of dosing with a once-daily 200 mg dose of ALS-2200 in combination with ribavirin in people with genotype 1 chronic hepatitis C who were new to treatment (n=8). Five patients achieved HCV RNA levels below the limit of quantification
Similar to previously announced data from the monotherapy cohort, ALS-2200 was well-tolerated, no patients discontinued due to adverse events and there were no serious adverse events. Data from the ALS-2200 study will be presented in an oral presentation at The Liver Meeting(R), the 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, November 9 to 13, 2012.
"Our goal is to develop all-oral regimens that are well-tolerated and provide a high rate of viral cure in a broad population of people with chronic hepatitis C," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "We're making good progress and expect to begin all-oral Phase 2 combination studies by the end of this year."
Pending discussions with regulatory agencies, Vertex is planning one Phase 2 study to evaluate ALS-2200 (VX-135) in combination with ribavirin, and one to evaluate ALS-2200 (VX-135) in combination with INCIVEK(R) (telaprevir), the company's approved protease inhibitor for people with genotype 1 chronic hepatitis C. These studies will evaluate 12 total weeks of treatment with a primary endpoint of SVR12 (sustained viral response:undetectable hepatitis C virus 12 weeks after the end of treatment) in people with genotype 1 chronic hepatitis C.
About ALS-2200
ALS-2200 is a uridine nucleotide analogue pro-drug that appears to have a high barrier to drug resistance based on in vitro studies. It is designed to inhibit the replication of the hepatitis C virus by acting on the NS5B polymerase. In vitro studies of the compound showed antiviral activity across all genotypes, or forms, of the hepatitis C virus, including genotypes more prevalent outside of the United States.
Vertex gained worldwide rights to ALS-2200 through an exclusive licensing agreement signed with Alios BioPharma, Inc. in June 2011. The agreement also includes a research program that will focus on the discovery of additional nucleotide analogues that act on hepatitis C polymerase. Vertex has the option to select additional compounds for development emerging from the research program.
About INCIVEK
INCIVEK(R) (telaprevir) tablets is an oral medicine that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication.
INCIVEK was approved by the U.S. Food and Drug Administration (FDA) in May 2011 and by Health Canada in August 2011 for use in combination with pegylated-interferon and ribavirin for adults with genotype 1 chronic hepatitis C with compensated liver disease (some level of damage to the liver but the liver still functions), including cirrhosis (scarring of the liver). INCIVEK is approved for people who are new to treatment, and for people who were treated previously with interferon-based treatment but who did not achieve a sustained viral response, or viral cure (relapsers, partial responders and null responders).
Vertex developed telaprevir in collaboration with Janssen and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America where it is being marketed under the brand name INCIVEK (in-SEE-veck). Janssen has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. In September 2011, telaprevir was approved in the European Union and Switzerland. Telaprevir is known as INCIVO(R) in Europe. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries. In September 2011, telaprevir was approved in Japan and is known as Telavic(R).
IMPORTANT SAFETY INFORMATION
Indication
INCIVEK(R) (telaprevir) is a prescription medicine used with the medicines peginterferon alfa and ribavirin to treat chronic (lasting a long time) hepatitis C genotype 1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatment. It is not known if INCIVEK is safe and effective in children under 18 years of age.
Important Safety Information
INCIVEK should always be taken in combination with peginterferon alfa and ribavirin. Ribavirin may cause birth defects or death of an unborn baby. Therefore, a patient should not take INCIVEK combination treatment if she is pregnant or may become pregnant, or if he is a man with a sexual partner who is pregnant. Patients must use two forms of effective birth control during treatment and for the 6 months after treatment with these medicines. Hormonal forms of birth control, including birth control pills, vaginal rings, implants or injections, may not work during treatment with INCIVEK.
INCIVEK and other medicines can affect each other and can also cause side effects that can be serious or life threatening. There are certain medicines patients cannot take with INCIVEK combination treatment. Patients should tell their healthcare providers about all the medicines they take, including prescription and non-prescription medicines, vitamins and herbal supplements.
INCIVEK can cause serious side effects including skin reactions, rash and anemia that can be severe. The most common side effects of INCIVEK include itching, nausea, diarrhea, vomiting, anal or rectal problems, taste changes and tiredness. There are other possible side effects of INCIVEK, and side effects associated with peginterferon alfa and ribavirin also apply to INCIVEK combination treatment. Patients should tell their healthcare providers about any side effect that bothers them or doesn't go away.
Please see full Prescribing Information for INCIVEK including the Medication Guide, available at www.INCIVEK.com .
About Hepatitis C
Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.(1) Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.(1) Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.(1)
Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured.(2) However, approximately 60 percent of people do not achieve SVR,(3,4,5)or viral cure,(6) after treatment with 48 weeks of pegylated-interferon and ribavirin alone. If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.(7,8)
More than 170 million people worldwide are chronically infected with hepatitis C.(6) In the United States, up to 5 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.(9,10)Hepatitis C is four times more prevalent in the United States compared to HIV.(10) The majority of people with hepatitis C in the United States were born between 1945 and 1965, accounting 82 percent of people with the disease.(11)Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 15,000 deaths annually.(12,13)By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.(10)
About Vertex
Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.
Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, rheumatoid arthritis and other life-threatening diseases.
Founded more than 20 years ago in Cambridge, Mass., we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada. Today, Vertex has more than 2,000 employees around the world, and for three years in a row, Science magazine has named Vertex one of its Top Employers in the life sciences.
Vertex's press releases are available at www.vrtx.com .
About Alios BioPharma
Alios BioPharma is a biotechnology company located in South San Francisco, California, that is developing novel medicines aimed at the treatment of viral diseases. Alios has an innovative team of highly experienced scientists and clinical researchers who are developing direct acting antiviral agents against several human viral pathogens of public health importance including HCV, RSV, Influenza and other chronic, acute and emerging viral diseases. The overall goal for the Alios therapeutic platform is to maximize patient benefits in areas of high unmet medical need through optimization of potency, safety and tolerability.
Special Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, Dr. Kauffman's statements in the third paragraph of this press release and statements regarding (i) data supporting the advancement of ALS-2200 into Phase 2 all-oral studies this year and (ii) Vertex's plans regarding the design of these Phase 2 studies. While the company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the initiation of Phase 2 studies of ALS-2200 may be delayed or prevented, outcomes from any future studies of ALS-2200 may not be favorable and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through Vertex's website at www.vrtx.com . Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
(VRTX-GEN)
References:
(1) Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf Updated June 2010. Accessed September 21, 2012.
(2) Pearlman BL and Traub N. Sustained Virologic Response to Antiviral Therapy for Chronic Hepatitis C Virus Infection: A Cure and So Much More. Clin Infect Dis. 2011 Apr;52(7):889-900.
(3) Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.
(4) Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.
(5) McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.
(6) Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.
(7) Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).
(8) Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.
(9) Chak, E, et. al. Hepatitis C Virus Infection In USA: An Estimate of True Prevalence. Liver Intl. 2011;1096 -1098.
(10) Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. Available at: http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx Updated January 11, 2010. Accessed September 21, 2012.
(11) Smith, BD, et al. Hepatitis C Virus Antibody Prevalence, Correlates and Predictors among Persons Born from 1945 through 1965, United States, 1999-2008. AASLD 2011 Annual Meeting.
(12) Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.
(13) S.D. Holmberg, K.N. Ly., et.al. The Growing Burden of Mortality Associated with Viral Hepatitis in the United States, 1999-2007. AASLD 2011 Annual Meeting.
SOURCE: Vertex Pharmaceuticals Incorporated
Thursday, July 12, 2012
Levels of Hepatitis C Virus Higher Among African-Americans and Males
Posted on 7/10/12 on www.amren.com. A collaborative study between the National Institutes of Health Clinical Center and UCSF to be published in the July issue of "Hepatology" showed that among IVDUs males and African Americans were more likely to have HCV and/or HIV than any other demographic. This has implications for treatment in that African Americans are less likely to respond to current therapy than any other demographic.
Levels of Hepatitis C Virus Higher Among African-Americans and Males
Medical Xpress, July 10, 2012
Epidemiologists have determined that levels of hepatitis C virus (HCV) found among injection drug users (IDUs) were higher in individuals who are male or African American even after differences in other factors were considered. The study, which was funded by the National Cancer Institute and performed with collaborators from the National Institutes of Health Clinical Center and the University of California—San Francisco, was the first to simultaneously examine the association of demographic, viral and human genetic factors on HCV RNA levels. Results of the study published in the July issue of Hepatology, a journal of the American Association for the Study of Liver Diseases (AASLD), also showed higher levels of HCV among IDUs who were co-infected with human immunodeficiency virus (HIV).
A 2010 report from the Centers for Disease Control and Prevention (CDC) estimates that up to 3.9 million Americans have chronic HCV—a leading cause of liver cancer, end-stage liver disease and liver transplantation. According to the CDC 17,000 new cases and 2,800 acute cases of HCV were reported in 2010. Previous epidemiologic studies suggest one-third of those 18 to 30 year-old IDUs and up to 90% of older IDUs are infected with HCV.
“With such a high incidence and prevalence of hepatitis C virus infection among IDUs, it is important to understand the characteristics of the infection in this group,” explains lead author Dr. Thomas O’Brien of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute in Rockville, MD. “The HCV RNA level is an important predictor of response to treatment in patients with chronic hepatitis C. Our study is the first to examine simultaneously the viral, demographic, and genetic factors that impact HCV levels in ethnically diverse IDUs.”
Participants were originally recruited for the Urban Health Study—a multi-ethnic group of IDUs in San Francisco. Researchers used interview data and biological samples from participants to analyze demographic, viral and host characteristics of cancer-causing viruses. A total of 1701 participants had detectable HCV RNA and were included in the present study. The median age at enrollment was 46 years and median age of first illicit drug injection was 18 years. Close to 75% of participants were men and 56% were African American, 34% European (non-Hispanic) and 7% Latino (non-African American).
Adjusted analysis revealed that age, gender, racial ancestry, HIV-1 infection, and IL28B rs12979860 genotype were all independently associated with the HCV RNA level. “We know that the level of HCV is an important predictor of treatment response and that these levels seem to be influenced by a number of demographic, clinical, viral and human genetic factors,” concludes Dr. O’Brien.
Monday, November 28, 2011
Seeking Alpha.com's Chris Katje on Gilead potential for antiviral dominance...
A bullish outlook for Gilead from Seeking Alpha author Chris Katje. His view is that Gilead will have market dominance in both HIV and HCV. He sees that Gilead will have full control of the Pharmasset HCV portfolio through the buyout, thus negating any worry about royalty payments. I'd also add the potential for co-formulation between Pharmasset's portfolio and Gilead's current HCV portfolio, which has always been Gilead's hallmark. An interesting read and it seems the rest of the market seems to agree with Katje, as Gilead stock has received several outlook upgrades from analysts. It just took some time for the initial sticker shock to wear off.
Acquisition of Pharmasset
Gilead Sciences (GILD) announced its intent to acquire Pharmasset (VRUS) for a whopping $11 billion on Monday morning. The deal has led many analysts and investors to question if Gilead overpaid for the deal. I think the deal is a great long-term play for the company and actually could present a buying opportunity of shares, which were down sharply after the announcement. Shares were up around five percent the following day after the announcement. Gilead will now be a large player in the HIV and Hepatitis markets.
Pharmasset has no drugs on the market, which is the biggest reason why people question the valuation. Drug candidate PSI-7977 appears to show enough promise that other companies were nibbling at acquiring the company. Gilead is confident in its acquisition and is funding the deal through cash and $6 billion in debt it is taking on. Hepatitis C is being targeted by this drug and it could actually save many Americans from the life threatening liver damage that is usually caused by the disease and leads to many liver transplants. The drug is expected to be filed with the Food and Drug Administration in 2014. Pharmasset owned the worldwide rights to the drug so Gilead will take full control and will not have to worry about licensing or royalty payments. Gilead now will be the leader in the race to find an all oral drug for the treatment of Hepatitis C.
Why the Acquisition and Hefty Premium
Gilead presented a slide show on its website shortly after the announcement to acquire Pharmasset. Gilead reconfirmed its goal of creating the best Hepatitis C drug, which would be determined by some of the following:
Taken Once Daily
Manageable Side Effects
Higher Cure Rates Than Current Drugs on the Market
Increased Treatments With a New Drug
Gilead has recognized that a combination of two or more drugs may be needed to create this super Hepatitis C drug. This is where I believe that Gilead’s acquisition will ultimately pay off. Gilead has combined several of its own drugs with products of other companies to create better acting and more effective drugs for patients.
Competition in Hepatitis C Market
Several other Hepatitis C drugs have popped up on the market recently. Victrelis is a drug owned by Merck (MRK), acquired through its acquisition of Schering Plough. The drug has so far been a disappointment as it only brought in $31 million of revenue in the third quarter reported on October 31, for Merck. Incivek, a drug owned by Vertex Pharmaceuticals (VRTX), on the other hand posted sales of $419 million in the past quarter. Analysts have already been lowering price targets of VRTX because of the likely competition from PS-7977 pending approval. Vertex will enjoy a couple of years of dominating market share before the competing drug enters the market. Annual sales could hit $2 to $3 billion for Vertex. Merck on the other hand is playing second fiddle and is likely to never see blockbuster status with its Hepatitis C drug.
Gilead’s Biggest Acquisitions
Gilead has a long history of acquiring other drug companies as many large drug companies do. Highlights include:
1999 Nexstar Pharmaceuticals - Gained two drugs through the acquisition. One, Ambisome, is still a marketed drug by Gilead. Deal seemed to be made more for the company’s intent on expanding in Europe.
2003 Triangle Pharmaceuticals - Emtriva, now a part of two Gilead drugs, was gained through this $464 million acquisition. Atripla and Truvada both use the component emtricitabine, a former Triangle product.
2006 Corrus Pharma - Has a current drug in Gilead’s pipeline aimed at treating Cystic Fibrosis.
2006 Myogen - Myogen was the most expensive acquisition previous to Pharmasset coming in at $2.5 billion. This has also been one of the most important and successful acquisitions made by Gilead as it brought three drugs, two marketed, and one currently sold by Gilead to the company.
2009 CV Therapeutics - Billion dollar purchase helped strengthen and diversify Gilead’s pool of drugs as it gained two drugs aimed at cardiovascular diseases.
Several other million dollar deals were made by Gilead over the last eight years. Gilead has made many of its acquisitions to strengthen its own technology and combine existing drugs with new ones.
Gilead’s Products
Gilead remains the market leader in drugs that treat the HIV virus. Its marketed products in the HIV market are:
Atripla is marketed with Bristol Myers Squibb (BMY) after its approval in 2006. The drug treats HIV and will lose patent expiration in 2021.
Complera is one of Gilead’s newest drugs on the market. It was approved by the FDA in August of 2011, and is co-marketed with Johnson and Johnson (JNJ).
Emtriva was approved in 2003 and will expire in 2021.
Truvada treats HIV and is one of Gilead’s top selling drugs. It was approved in 2004 and will lose its patent protection in 2021.
Viread treats Hepatitis B and HIV viruses. The drug was the first successfully launched HIV drug in 2001 by Gilead. The drug, which is a huge seller for Gilead, will lose patent protection in 2017.
Gilead has drugs in several other fields that compete with numerous other large drug companies. The other drugs currently on the market are:
Ambisome treats infections like fungal, meningitis, and Cryptococcus. The drug was approved in 1997 and will lose patent protection in 2016. The marketing partner on the drug is Astellas Pharma.
Cayston is Gilead’s cystic fibrosis drug that was approved in 2010. The drug has exclusive patent protection until 2021. Gilead markets the drug on its own and maintains all revenue from the drug.
Hepsera treats Hepatitis B and is owned and marketed by Gilead. The drug was approved in 2002 and its patent expires in 2014.
Letairis has since 2007 treated Pulmonary Hypertension. The drug is co-marketed with GlasxoSmithKline (GSK) and loses patent protection in 2015.
Lexiscan is a cardiovascular drug marketed with Astellas Pharma and it will lose patent protection in 2019.
Macugen is an age-related macular degeneration drug first approved in 2004, which is shared with Pfizer (PFE) and will lose patent protection in 2017.
Ranexa treats chest pain and will lose patent protection in 2019. The drug is co-marketed with Swiss drug company Roche.
Tamiflu treats the influenza virus as an oral capsule. The drug, which loses its patent protection in 2016, is licensed to Roche.
Vistide treats Cytomegalovirus and also certain eye problems involving the retina. The drug was founded in 1996 and has since lost its patent protection.
Gilead’s Pipeline
Gilead has twenty drugs listed on its site in current phases of trial. The drugs target HIV, Hepatitis C, numerous Cardiovascular diseases, Diabetes, Leukemia, Non-Hodgkin’s Lymphoma, and other diseases. Like many other large drug companies, Gilead has kept a strong pipeline targeting some of the biggest diseases affecting the world today. Three drugs targeting HIV are in Phase III trials currently. The Pharmasset acquisition will improve the company’s pipeline as it focuses on becoming a large player in the Hepatitis C market. Gilead will likely test several of its own Hepatitis drugs with Pharmasset products to create dual drugs much like it has with its HIV drugs.
The most important drug for Gilead in my opinion is known as the Quad. The drug combines Gilead’s own products and will help cut part of its revenue share with other marketing partners. The drug has held up well in trials. The drug will be brought in front of the FDA in 2012 and could be a substantial revenue earner for Gilead. The Quad drug is cutting down on symptoms from Gilead’s Atripla including dizziness, insomnia and depression. There are two trials testing Gilead drugs together in the Quad trials. Atripla had sales of $2.9 billion over the last year. However a portion of that revenue is given to Bristol Myers Squibb for its contribution to the drug. The approval of the quad pill could provide a nice bump to the share price in 2012.
Gilead’s Current Sales
Gilead is the leader in the HIV drug market and has shown its dominance. From the slide show presentation after the Pharmasset announcement it listed trailing twelve month revenue at $7.4 billion. The total market for HIV drugs is currently $13 billion so Gilead controls 50% of this blockbuster medical category. In the last fiscal year Gilead had earnings per share of $3.32 based on earnings of $2.9 billion.
Analysts call for earnings of $4.37 for the next fiscal year. With a closing share price of $39.28 on Friday, the price-to-earnings ratio is less than nine. According to Yahoo Finance, over 91% of the shares are currently held by institutions and mutual funds. More than 900 funds hold shares of Gilead as it represents one of the best plays on the healthcare and drugs industry.
Analyst Upgrades
Several days after the acquisition of Pharmasset was announced, analysts have upgraded shares. Citigroup and Bank of America both upgraded the shares after revaluating. Bank of America said that the company’s Hepatitis C program could some day be worth $15 to $30 billion. Gilead currently has a market capitalization of just under $30 billion so this deal could clearly define the company for the future.
My Share Valuation
I think the buyout of Pharmasset is a great purchase for Gilead. Gilead has made great use of drugs acquired through pipelines of companies it has bought out. Gilead absolutely owns the HIV drug market and the deal should help insure it gets a large portion of the Hepatitis C drug market in the future as well. For the coming year shares should trade closer to 12 times earnings, which would represent a share price of $52.44. The approval of the Quad drug as well as earnings announcements could power shares past $60. I think long term the company could double its market capitalization to $60 billion with its marketed HIV drugs and several Hepatitis C drugs on the market. I think shares would be a great purchase for an IRA as a bet on the company for the future.
Disclosure: I have no positions in any stocks mentioned, but may initiate a long position in GILD over the next 72 hours.
Acquisition of Pharmasset
Gilead Sciences (GILD) announced its intent to acquire Pharmasset (VRUS) for a whopping $11 billion on Monday morning. The deal has led many analysts and investors to question if Gilead overpaid for the deal. I think the deal is a great long-term play for the company and actually could present a buying opportunity of shares, which were down sharply after the announcement. Shares were up around five percent the following day after the announcement. Gilead will now be a large player in the HIV and Hepatitis markets.
Pharmasset has no drugs on the market, which is the biggest reason why people question the valuation. Drug candidate PSI-7977 appears to show enough promise that other companies were nibbling at acquiring the company. Gilead is confident in its acquisition and is funding the deal through cash and $6 billion in debt it is taking on. Hepatitis C is being targeted by this drug and it could actually save many Americans from the life threatening liver damage that is usually caused by the disease and leads to many liver transplants. The drug is expected to be filed with the Food and Drug Administration in 2014. Pharmasset owned the worldwide rights to the drug so Gilead will take full control and will not have to worry about licensing or royalty payments. Gilead now will be the leader in the race to find an all oral drug for the treatment of Hepatitis C.
Why the Acquisition and Hefty Premium
Gilead presented a slide show on its website shortly after the announcement to acquire Pharmasset. Gilead reconfirmed its goal of creating the best Hepatitis C drug, which would be determined by some of the following:
Taken Once Daily
Manageable Side Effects
Higher Cure Rates Than Current Drugs on the Market
Increased Treatments With a New Drug
Gilead has recognized that a combination of two or more drugs may be needed to create this super Hepatitis C drug. This is where I believe that Gilead’s acquisition will ultimately pay off. Gilead has combined several of its own drugs with products of other companies to create better acting and more effective drugs for patients.
Competition in Hepatitis C Market
Several other Hepatitis C drugs have popped up on the market recently. Victrelis is a drug owned by Merck (MRK), acquired through its acquisition of Schering Plough. The drug has so far been a disappointment as it only brought in $31 million of revenue in the third quarter reported on October 31, for Merck. Incivek, a drug owned by Vertex Pharmaceuticals (VRTX), on the other hand posted sales of $419 million in the past quarter. Analysts have already been lowering price targets of VRTX because of the likely competition from PS-7977 pending approval. Vertex will enjoy a couple of years of dominating market share before the competing drug enters the market. Annual sales could hit $2 to $3 billion for Vertex. Merck on the other hand is playing second fiddle and is likely to never see blockbuster status with its Hepatitis C drug.
Gilead’s Biggest Acquisitions
Gilead has a long history of acquiring other drug companies as many large drug companies do. Highlights include:
1999 Nexstar Pharmaceuticals - Gained two drugs through the acquisition. One, Ambisome, is still a marketed drug by Gilead. Deal seemed to be made more for the company’s intent on expanding in Europe.
2003 Triangle Pharmaceuticals - Emtriva, now a part of two Gilead drugs, was gained through this $464 million acquisition. Atripla and Truvada both use the component emtricitabine, a former Triangle product.
2006 Corrus Pharma - Has a current drug in Gilead’s pipeline aimed at treating Cystic Fibrosis.
2006 Myogen - Myogen was the most expensive acquisition previous to Pharmasset coming in at $2.5 billion. This has also been one of the most important and successful acquisitions made by Gilead as it brought three drugs, two marketed, and one currently sold by Gilead to the company.
2009 CV Therapeutics - Billion dollar purchase helped strengthen and diversify Gilead’s pool of drugs as it gained two drugs aimed at cardiovascular diseases.
Several other million dollar deals were made by Gilead over the last eight years. Gilead has made many of its acquisitions to strengthen its own technology and combine existing drugs with new ones.
Gilead’s Products
Gilead remains the market leader in drugs that treat the HIV virus. Its marketed products in the HIV market are:
Atripla is marketed with Bristol Myers Squibb (BMY) after its approval in 2006. The drug treats HIV and will lose patent expiration in 2021.
Complera is one of Gilead’s newest drugs on the market. It was approved by the FDA in August of 2011, and is co-marketed with Johnson and Johnson (JNJ).
Emtriva was approved in 2003 and will expire in 2021.
Truvada treats HIV and is one of Gilead’s top selling drugs. It was approved in 2004 and will lose its patent protection in 2021.
Viread treats Hepatitis B and HIV viruses. The drug was the first successfully launched HIV drug in 2001 by Gilead. The drug, which is a huge seller for Gilead, will lose patent protection in 2017.
Gilead has drugs in several other fields that compete with numerous other large drug companies. The other drugs currently on the market are:
Ambisome treats infections like fungal, meningitis, and Cryptococcus. The drug was approved in 1997 and will lose patent protection in 2016. The marketing partner on the drug is Astellas Pharma.
Cayston is Gilead’s cystic fibrosis drug that was approved in 2010. The drug has exclusive patent protection until 2021. Gilead markets the drug on its own and maintains all revenue from the drug.
Hepsera treats Hepatitis B and is owned and marketed by Gilead. The drug was approved in 2002 and its patent expires in 2014.
Letairis has since 2007 treated Pulmonary Hypertension. The drug is co-marketed with GlasxoSmithKline (GSK) and loses patent protection in 2015.
Lexiscan is a cardiovascular drug marketed with Astellas Pharma and it will lose patent protection in 2019.
Macugen is an age-related macular degeneration drug first approved in 2004, which is shared with Pfizer (PFE) and will lose patent protection in 2017.
Ranexa treats chest pain and will lose patent protection in 2019. The drug is co-marketed with Swiss drug company Roche.
Tamiflu treats the influenza virus as an oral capsule. The drug, which loses its patent protection in 2016, is licensed to Roche.
Vistide treats Cytomegalovirus and also certain eye problems involving the retina. The drug was founded in 1996 and has since lost its patent protection.
Gilead’s Pipeline
Gilead has twenty drugs listed on its site in current phases of trial. The drugs target HIV, Hepatitis C, numerous Cardiovascular diseases, Diabetes, Leukemia, Non-Hodgkin’s Lymphoma, and other diseases. Like many other large drug companies, Gilead has kept a strong pipeline targeting some of the biggest diseases affecting the world today. Three drugs targeting HIV are in Phase III trials currently. The Pharmasset acquisition will improve the company’s pipeline as it focuses on becoming a large player in the Hepatitis C market. Gilead will likely test several of its own Hepatitis drugs with Pharmasset products to create dual drugs much like it has with its HIV drugs.
The most important drug for Gilead in my opinion is known as the Quad. The drug combines Gilead’s own products and will help cut part of its revenue share with other marketing partners. The drug has held up well in trials. The drug will be brought in front of the FDA in 2012 and could be a substantial revenue earner for Gilead. The Quad drug is cutting down on symptoms from Gilead’s Atripla including dizziness, insomnia and depression. There are two trials testing Gilead drugs together in the Quad trials. Atripla had sales of $2.9 billion over the last year. However a portion of that revenue is given to Bristol Myers Squibb for its contribution to the drug. The approval of the quad pill could provide a nice bump to the share price in 2012.
Gilead’s Current Sales
Gilead is the leader in the HIV drug market and has shown its dominance. From the slide show presentation after the Pharmasset announcement it listed trailing twelve month revenue at $7.4 billion. The total market for HIV drugs is currently $13 billion so Gilead controls 50% of this blockbuster medical category. In the last fiscal year Gilead had earnings per share of $3.32 based on earnings of $2.9 billion.
Analysts call for earnings of $4.37 for the next fiscal year. With a closing share price of $39.28 on Friday, the price-to-earnings ratio is less than nine. According to Yahoo Finance, over 91% of the shares are currently held by institutions and mutual funds. More than 900 funds hold shares of Gilead as it represents one of the best plays on the healthcare and drugs industry.
Analyst Upgrades
Several days after the acquisition of Pharmasset was announced, analysts have upgraded shares. Citigroup and Bank of America both upgraded the shares after revaluating. Bank of America said that the company’s Hepatitis C program could some day be worth $15 to $30 billion. Gilead currently has a market capitalization of just under $30 billion so this deal could clearly define the company for the future.
My Share Valuation
I think the buyout of Pharmasset is a great purchase for Gilead. Gilead has made great use of drugs acquired through pipelines of companies it has bought out. Gilead absolutely owns the HIV drug market and the deal should help insure it gets a large portion of the Hepatitis C drug market in the future as well. For the coming year shares should trade closer to 12 times earnings, which would represent a share price of $52.44. The approval of the Quad drug as well as earnings announcements could power shares past $60. I think long term the company could double its market capitalization to $60 billion with its marketed HIV drugs and several Hepatitis C drugs on the market. I think shares would be a great purchase for an IRA as a bet on the company for the future.
Disclosure: I have no positions in any stocks mentioned, but may initiate a long position in GILD over the next 72 hours.
Monday, November 14, 2011
Milk Thistle shows no effect according to data presented at AASLD...
(From MEDPAGE.com: Data from AASLD concludes that silymarin. the active compound in the botanical Milk Thistle long believed to have antiviral and liver rejuvenating effects has neither compared to placebo. Important info for patients long misled by claims from unscrupulous vendors)
SAN FRANCISCO -- A botanical agent used in the treatment of liver disorders had no detectable effect on hepatitis C virus (HCV) disease activity in comparison with placebo in patients with previously treated chronic disease, results of a randomized trial showed.
Patients treated for six months with either of two doses of silymarin had little change in levels of the liver enzyme alanine transaminase (ALT). About 4% of patients in each silymarin arm and in the placebo group met the primary endpoint of a decline in ALT to ≤45 IU or at least a 50% decline from baseline.
"Similarly, symptom scores and quality of life measures were unchanged during silymarin treatment," Michael W. Fried, MD, of the University of North Carolina in Chapel Hill, reported here at the American Association for the Study of Liver Diseases meeting.
The trial was perhaps the first to use a single, well-described silymarin preparation, and the doses employed in the study were five to seven times higher than customary doses, he added.
Silymarin is an extract of milk thistle and has long been used as a treatment for various types of liver disorders. A mixture of flavonolignans, silymarin has demonstrated anti-inflammatory and immunodulatory properties in vitro, as well as activity against the HCV core and virus-associated gene expression.
The substance has been evaluated in clinical trials as a therapeutic aid for cirrhosis, alcoholic liver disease, and viral hepatitis. However, the results have been inconsistent.
"Previous studies have been confounded by a lack of well-defined efficacy endpoints, inclusion of heterogeneous populations of patients with liver disease, and use of nonstandardized silymarin preparations," said Fried.
To address some of the shortcomings of previous clinical studies, the investigators designed a trial to evaluate silymarin as a potential aid in the treatment of chronic HCV that had not responded to interferon-based therapy.
All of the 154 patients enrolled at four centers in the U.S. had a history of treatment with interferon-based therapy and had not achieved a sustained virologic response. The patients had quantifiable HCV RNA and a serum ALT ≥65 IU.
The silymarin preparation used for the trial is produced in the Netherlands under the brand name Legalon 140 and is approved as a prescription drug in some European and Asian countries. The customary dose is 140 mg three times a day.
Eligible patients were randomized to one of two doses of silymarin (420 or 700 mg) or placebo. Patients in the high-dose silymarin arm took five capsules of the botanical agent three times daily. Patients randomized to the standard dose took three silymarin capsules and two placebo capsules three times each day, and patients in the placebo arm took five matching capsules three times daily.
The high-dose arm was based on results from a phase I dose-finding trial "in order to provide the highest likelihood of finding a therapeutic benefit," said Fried.
The primary endpoint, measured after 24 weeks, was a decline in serum ALT to ≤45 IU (the upper limit of normal) or a decline of at least 50% from baseline and <65 IU (1.5 times the upper limit of normal).
The patients were randomized to the three treatment arms. The three groups did not differ with respect to baseline demographic and clinical characteristics. Median age was 55, about 70% were white, about 90% had HCV genotype 1, about a fourth of the patients had evidence of cirrhosis, and 40% to 45% had a history of milk thistle use.
Adherence was good, said Fried, as about 90% of the study participants consumed more than 80% of their medication doses.
After six months, one person in the placebo group had a serum ALT ≤45 IU, as did two patients in each of the silymarin arms. Additionally, two patients in the placebo and high-dose silymarin groups had at least a 50% decline in baseline ALT to <65 IU, as did one patient in the 420-mg silymarin arm.
The proportion of patients who met either definition of the primary endpoint was 3.8% (two of 52) in the placebo group, 4% (two of 50) in the 420-mg silymarin arm, and 3.8% (two of 52) in the high-dose silymarin arm.
The three groups also did not differ significantly with respect to the mean change in ALT, change in HCV RNA, or scores on a battery of quality-of-life instruments. A graph of serum ALT levels throughout the six months showed virtually superimposable lines for the three groups.
The placebo and silymarin groups also did not differ significantly in their adverse-event profiles. The most common types of adverse events were gastrointestinal, musculoskeletal, dermatologic, infection, and physical injury. Six patients in the 420-mg silymarin arm and five in the 700-mg arm had serious adverse events, compared with one in the placebo group.
During the discussion that followed the presentation, Fried expressed doubt that using even higher doses of silymarin might lead to better results, as suggested by a member of the audience.
AASLD president T. Jake Liang, MD, said the study is informative because the results showed not only that silymarin performed no better than placebo in a well-controlled clinical trial but also that the substance is not harmful for people who take it for liver conditions.
SAN FRANCISCO -- A botanical agent used in the treatment of liver disorders had no detectable effect on hepatitis C virus (HCV) disease activity in comparison with placebo in patients with previously treated chronic disease, results of a randomized trial showed.
Patients treated for six months with either of two doses of silymarin had little change in levels of the liver enzyme alanine transaminase (ALT). About 4% of patients in each silymarin arm and in the placebo group met the primary endpoint of a decline in ALT to ≤45 IU or at least a 50% decline from baseline.
"Similarly, symptom scores and quality of life measures were unchanged during silymarin treatment," Michael W. Fried, MD, of the University of North Carolina in Chapel Hill, reported here at the American Association for the Study of Liver Diseases meeting.
The trial was perhaps the first to use a single, well-described silymarin preparation, and the doses employed in the study were five to seven times higher than customary doses, he added.
Silymarin is an extract of milk thistle and has long been used as a treatment for various types of liver disorders. A mixture of flavonolignans, silymarin has demonstrated anti-inflammatory and immunodulatory properties in vitro, as well as activity against the HCV core and virus-associated gene expression.
The substance has been evaluated in clinical trials as a therapeutic aid for cirrhosis, alcoholic liver disease, and viral hepatitis. However, the results have been inconsistent.
"Previous studies have been confounded by a lack of well-defined efficacy endpoints, inclusion of heterogeneous populations of patients with liver disease, and use of nonstandardized silymarin preparations," said Fried.
To address some of the shortcomings of previous clinical studies, the investigators designed a trial to evaluate silymarin as a potential aid in the treatment of chronic HCV that had not responded to interferon-based therapy.
All of the 154 patients enrolled at four centers in the U.S. had a history of treatment with interferon-based therapy and had not achieved a sustained virologic response. The patients had quantifiable HCV RNA and a serum ALT ≥65 IU.
The silymarin preparation used for the trial is produced in the Netherlands under the brand name Legalon 140 and is approved as a prescription drug in some European and Asian countries. The customary dose is 140 mg three times a day.
Eligible patients were randomized to one of two doses of silymarin (420 or 700 mg) or placebo. Patients in the high-dose silymarin arm took five capsules of the botanical agent three times daily. Patients randomized to the standard dose took three silymarin capsules and two placebo capsules three times each day, and patients in the placebo arm took five matching capsules three times daily.
The high-dose arm was based on results from a phase I dose-finding trial "in order to provide the highest likelihood of finding a therapeutic benefit," said Fried.
The primary endpoint, measured after 24 weeks, was a decline in serum ALT to ≤45 IU (the upper limit of normal) or a decline of at least 50% from baseline and <65 IU (1.5 times the upper limit of normal).
The patients were randomized to the three treatment arms. The three groups did not differ with respect to baseline demographic and clinical characteristics. Median age was 55, about 70% were white, about 90% had HCV genotype 1, about a fourth of the patients had evidence of cirrhosis, and 40% to 45% had a history of milk thistle use.
Adherence was good, said Fried, as about 90% of the study participants consumed more than 80% of their medication doses.
After six months, one person in the placebo group had a serum ALT ≤45 IU, as did two patients in each of the silymarin arms. Additionally, two patients in the placebo and high-dose silymarin groups had at least a 50% decline in baseline ALT to <65 IU, as did one patient in the 420-mg silymarin arm.
The proportion of patients who met either definition of the primary endpoint was 3.8% (two of 52) in the placebo group, 4% (two of 50) in the 420-mg silymarin arm, and 3.8% (two of 52) in the high-dose silymarin arm.
The three groups also did not differ significantly with respect to the mean change in ALT, change in HCV RNA, or scores on a battery of quality-of-life instruments. A graph of serum ALT levels throughout the six months showed virtually superimposable lines for the three groups.
The placebo and silymarin groups also did not differ significantly in their adverse-event profiles. The most common types of adverse events were gastrointestinal, musculoskeletal, dermatologic, infection, and physical injury. Six patients in the 420-mg silymarin arm and five in the 700-mg arm had serious adverse events, compared with one in the placebo group.
During the discussion that followed the presentation, Fried expressed doubt that using even higher doses of silymarin might lead to better results, as suggested by a member of the audience.
AASLD president T. Jake Liang, MD, said the study is informative because the results showed not only that silymarin performed no better than placebo in a well-controlled clinical trial but also that the substance is not harmful for people who take it for liver conditions.
Monday, November 7, 2011
Pharmasset's HCV nucleotide analog PSI-7977 poised to raise the bar for HCV DAAs....
By far the biggest buzz at AASLD thus far has been the performance of Pharmasset's PSI-7977, a nucleotide analog being studied in various combinations for the treatment of chronic hepatitis C. Pharmasset released Phase II data at AASLD showing 100% SVR in a small group of genotype 2/3 patients in combination with ribavirin but without the need for interferon. The success despite the lack of interferon raised hopes for a truly interferon-free pan-genotypic treatment for HCV with once daily dosing and a minimum amount of side effects. The drug has a long way to go in development, but this data certainly buoyed hopes of patients, HCV providers and investors alike. One hopes that the data for prior non-responders (especially null-responders) and genotype 1 patients fair as well.
Twelve Weeks Interferon-Free PSI-7977 Regimen Cures 100 Percent Hep C Genotype 2/3
A twelve-week course of Pharmasset’s once-daily experimental nucleotide analog PSI-7977, combined with ribavirin, cured 10 of 10 people living with genotype 2/3 hepatitis C virus (HCV) who used the regimen—without pegylated interferon—in a Phase II clinical trial. The highly encouraging results were reported Sunday, November 6, at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco.
Compared with the three other groups included in the study, which involved taking PSI-7977 plus ribavirin with either four, eight or 12 weeks of pegylated interferon, significant improvements in safety and tolerability were also documented among those using PSI-7977 plus ribavirin alone, according to Edward Gane, MD, of the Auckland City Hospital in Auckland, New Zealand, and his ELECTRON study colleagues.
Results from early studies of PSI-7977 have been promising. In the PROTON study, PSI-7977 combined with pegylated interferon plus ribavirin resulted in sustained virologic responses (SVRs)—viral cures—in 96 percent of study volunteers with HCV genotype 2/3 and 91 percent of those with HCV genotype 1 (the most common yet hardest-to-treat form of the virus in the United States).
ELECTRON, initiated in December 2010, was conducted to determine the shortest duration of pegylated interferon—if any—required to achieve SVRs when PSI-7977 plus ribavirin are given for 12 weeks. HCV genotype 2/3 patients were initially selected for this unorthodox study—pegylated interferon has long been a mainstay agent in hepatitis C drug regimens—given pegylated interferon and ribavirin tend to be much more effective for individuals with genotype 2/3 virus and could be called upon in the event of poor responses to PSI-7977/ribavirin in the study.
No “rescue” therapy proved necessary. At virtually all study time points—weeks 4, 8 and 12 during therapy and weeks 4, 8, 12 and 24 following the completion of treatment—100 percent of the patients in each group maintained undetectable HCV viral loads. Eleven patients received PSI-7977/ribavirin plus 12 weeks of pegylated interferon, 10 received PSI-7977/ribavirin plus eight weeks of pegylated interferon, nine received PSI-7977/ribavirin plus pegylated interferon and ten received PSI-7977/ribavirin without pegylated interferon.
Gane noted that HCV viral load suppression was rapid in all four treatment groups—virtually everyone had HCV below the level of detection within three weeks of beginning treatment.
At least one side effect—including headache, fatigue, depression, insomnia, anxiety, irritability, muscle soreness and upper respiratory tract infections—was more likely to be documented in those in the 12-week pegylated interferon group (72 percent), compared with those who didn’t receive any pegylated interferon (40 percent).
Similarly, whereas moderate-to-severe drops in neutrophils—a type of white blood cell—was documented in roughly 70 percent of those in the 12-week pegylated interferon group, no volunteers in the interferon-free PSI-7977/ribavirin group experienced this toxicity. Interferon-free PSI-7977 plus ribavirin also had much less of an impact on hemoglobin levels, a marker of anemia.
Also encouraging, all patients in the study experienced a rapid normalization of ALT, a key liver enzyme. Among those in the interferon-free treatment group, normal ALT levels were documented in all patients by the end of the third week of treatment.
In summary, Gane noted, “PSI-7977 [400 milligrams once daily] remains very well tolerated with no attributable safety signal, no treatment discontinuations and no treatment emergency laboratory abnormalities.” As for potency, he concluded that PSI-7977/ribavirin “elicited rapid suppression” of HCV viral load in study volunteers with HCV genotype 2 or 3 and that all 40 patients in the study achieved an SVR, regardless of whether or not interferon was used. Additionally, not a single case of drug-resistant virus emerged during the study.
Further results from ELECTRON are expected. The study has been amended, adding several new treatment groups. One group is exploring PSI-7977 used as monotherapy—without pegylated interferon or ribavirin—to treat genotype 2/3 infection. Preliminary data reported by Gane's team suggest that four patients in this group have maintained undetectable HCV levels four weeks after discontinuing treatment.
Another group is studying PSI-7977 in combination with pegylated interferon plus ribavirin, again in genotype 2/3 patients, but for only eight weeks.
Three additional groups are now enrolling patients. One is studying 12 weeks of PSI-7977 plus ribavirin, without interferon, in HCV genotype 2/3 patients who weren't able to clear the virus with 24 weeks of previous pegylated interferon/ribavirin therapy. A second is evaluating PSI-7977 plus ribavirin in HCV genotype 1 patients beginning therapy for the first time. The third group consists of individuals with HCV genotype 1 null responders (patients who responded very poorly to prior pegylated interferon/ribavirin treatment); they will receive PSI-7977/ribavirin for a total of 12 weeks.
Pharmasset recently announced its Phase III clinical trial program. Two studies—FISSION and POSITRON—will further explore the safety and efficacy of PSI-7977 plus ribavirin, but without pegylated interferon, in approximately 725 people with genotype 2/3 HCV infection. A third study will explore PSI-7977 in HCV genotype 1 patients, with the design of the study determined by the ongoing ELECTRON clinical trial and another study still under way.
Read the full article here: http://www.aidsmeds.com/articles/psi7977_svr_hcv_1667_21405.shtml
Twelve Weeks Interferon-Free PSI-7977 Regimen Cures 100 Percent Hep C Genotype 2/3
A twelve-week course of Pharmasset’s once-daily experimental nucleotide analog PSI-7977, combined with ribavirin, cured 10 of 10 people living with genotype 2/3 hepatitis C virus (HCV) who used the regimen—without pegylated interferon—in a Phase II clinical trial. The highly encouraging results were reported Sunday, November 6, at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco.
Compared with the three other groups included in the study, which involved taking PSI-7977 plus ribavirin with either four, eight or 12 weeks of pegylated interferon, significant improvements in safety and tolerability were also documented among those using PSI-7977 plus ribavirin alone, according to Edward Gane, MD, of the Auckland City Hospital in Auckland, New Zealand, and his ELECTRON study colleagues.
Results from early studies of PSI-7977 have been promising. In the PROTON study, PSI-7977 combined with pegylated interferon plus ribavirin resulted in sustained virologic responses (SVRs)—viral cures—in 96 percent of study volunteers with HCV genotype 2/3 and 91 percent of those with HCV genotype 1 (the most common yet hardest-to-treat form of the virus in the United States).
ELECTRON, initiated in December 2010, was conducted to determine the shortest duration of pegylated interferon—if any—required to achieve SVRs when PSI-7977 plus ribavirin are given for 12 weeks. HCV genotype 2/3 patients were initially selected for this unorthodox study—pegylated interferon has long been a mainstay agent in hepatitis C drug regimens—given pegylated interferon and ribavirin tend to be much more effective for individuals with genotype 2/3 virus and could be called upon in the event of poor responses to PSI-7977/ribavirin in the study.
No “rescue” therapy proved necessary. At virtually all study time points—weeks 4, 8 and 12 during therapy and weeks 4, 8, 12 and 24 following the completion of treatment—100 percent of the patients in each group maintained undetectable HCV viral loads. Eleven patients received PSI-7977/ribavirin plus 12 weeks of pegylated interferon, 10 received PSI-7977/ribavirin plus eight weeks of pegylated interferon, nine received PSI-7977/ribavirin plus pegylated interferon and ten received PSI-7977/ribavirin without pegylated interferon.
Gane noted that HCV viral load suppression was rapid in all four treatment groups—virtually everyone had HCV below the level of detection within three weeks of beginning treatment.
At least one side effect—including headache, fatigue, depression, insomnia, anxiety, irritability, muscle soreness and upper respiratory tract infections—was more likely to be documented in those in the 12-week pegylated interferon group (72 percent), compared with those who didn’t receive any pegylated interferon (40 percent).
Similarly, whereas moderate-to-severe drops in neutrophils—a type of white blood cell—was documented in roughly 70 percent of those in the 12-week pegylated interferon group, no volunteers in the interferon-free PSI-7977/ribavirin group experienced this toxicity. Interferon-free PSI-7977 plus ribavirin also had much less of an impact on hemoglobin levels, a marker of anemia.
Also encouraging, all patients in the study experienced a rapid normalization of ALT, a key liver enzyme. Among those in the interferon-free treatment group, normal ALT levels were documented in all patients by the end of the third week of treatment.
In summary, Gane noted, “PSI-7977 [400 milligrams once daily] remains very well tolerated with no attributable safety signal, no treatment discontinuations and no treatment emergency laboratory abnormalities.” As for potency, he concluded that PSI-7977/ribavirin “elicited rapid suppression” of HCV viral load in study volunteers with HCV genotype 2 or 3 and that all 40 patients in the study achieved an SVR, regardless of whether or not interferon was used. Additionally, not a single case of drug-resistant virus emerged during the study.
Further results from ELECTRON are expected. The study has been amended, adding several new treatment groups. One group is exploring PSI-7977 used as monotherapy—without pegylated interferon or ribavirin—to treat genotype 2/3 infection. Preliminary data reported by Gane's team suggest that four patients in this group have maintained undetectable HCV levels four weeks after discontinuing treatment.
Another group is studying PSI-7977 in combination with pegylated interferon plus ribavirin, again in genotype 2/3 patients, but for only eight weeks.
Three additional groups are now enrolling patients. One is studying 12 weeks of PSI-7977 plus ribavirin, without interferon, in HCV genotype 2/3 patients who weren't able to clear the virus with 24 weeks of previous pegylated interferon/ribavirin therapy. A second is evaluating PSI-7977 plus ribavirin in HCV genotype 1 patients beginning therapy for the first time. The third group consists of individuals with HCV genotype 1 null responders (patients who responded very poorly to prior pegylated interferon/ribavirin treatment); they will receive PSI-7977/ribavirin for a total of 12 weeks.
Pharmasset recently announced its Phase III clinical trial program. Two studies—FISSION and POSITRON—will further explore the safety and efficacy of PSI-7977 plus ribavirin, but without pegylated interferon, in approximately 725 people with genotype 2/3 HCV infection. A third study will explore PSI-7977 in HCV genotype 1 patients, with the design of the study determined by the ongoing ELECTRON clinical trial and another study still under way.
Read the full article here: http://www.aidsmeds.com/articles/psi7977_svr_hcv_1667_21405.shtml
Monday, October 3, 2011
Vertex to Present New Data from Hepatitis C Development Program at AASLD Annual Meeting
Vertex to Present New Data from Hepatitis C Development Program at AASLD Annual Meeting
- Late-Breaker Presentations Include Phase 2 Data from INCIVEK-Based Combination Regimen in HIV/HCV Co-Infection and Short Duration Treatment with a Four-Drug Regimen Including INCIVEK and VX-222 -
CAMBRIDGE, Mass., Sep 30, 2011 (BUSINESS WIRE) -- Vertex Pharmaceuticals Incorporated VRTX +4.67% today announced that abstracts from its hepatitis C program, including two late-breaking posters from studies of INCIVEK(TM) (telaprevir) tablets and VX-222, were accepted for presentation at The Liver Meeting(R), the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco, November 4-8, 2011.
New data, including sustained viral response (SVR, or viral cure) results, from a Phase 2 study evaluating short durations of 12- and 24-week regimens of VX-222 in combination with INCIVEK (in-SEE-veck), pegylated-interferon and ribavirin in people with genotype 1 chronic hepatitis C who were new to treatment will be presented for the first time. Additionally, new data from a Phase 2 study evaluating INCIVEK combination treatment in people co-infected with genotype 1 chronic hepatitis C and human immunodeficiency virus (HIV) will be presented at the meeting. All people in this study were new to hepatitis C treatment.
"INCIVEK combination therapy has successfully increased viral cure rates and shortened total treatment time for the majority of people with hepatitis C who are being treated for the first time, but we have more to do," said Peter Mueller, Ph.D., Chief Scientific Officer and Executive Vice President of Global Research and Development at Vertex. "Our ongoing research is aimed at further improving treatment for hepatitis C by exploring the use of INCIVEK among those in critical need of more effective medicines and evaluating combinations, including some without interferon, that may offer higher cure rates and shorter treatment times."
The accepted abstracts are now available on the AASLD website at https://www.aasld.org/lm2011 .
INCIVEK Oral Presentations
1. #31: "Efficacy and safety of telaprevir-based regimens in cirrhotic patients with HCV genotype 1 and prior peginterferon/ribavirin treatment failure: subanalysis of the REALIZE Phase III study." November 6, 2011, 3:00 p.m. PDT.
2. #32: "Predictors of virologic response with telaprevir-based combination treatment in HCV genotype 1-infected patients with prior peginterferon/ribavirin treatment failure: post-hoc analysis of the Phase III REALIZE study." November 6, 2011, 3:15 p.m. PDT.
3. #35: "Retreatment with telaprevir/Peg-IFN/RBV after a short exposure to telaprevir in Phase I studies: interim results from a Phase IIIb rollover trial (C219)." November 6, 2011, 4:00 p.m. PDT.
4. #248: "Follow-up of SVR Durability and Viral Resistance in Patients with Chronic Hepatitis C Treated with Telaprevir-Based Regimens: Interim Analysis of the EXTEND Study." November 8, 2011, 11:00 a.m. PDT.
Vertex Late-Breaking Poster Presentations
1. #LB-8: "Telaprevir Combination with Peginterferon Alfa-2a/Ribavirin in HCV/HIV Coinfected Patients: 24-Week Treatment Interim Analysis." November 7, 2011.
2. #LB-14: "VX-222/telaprevir in Combination with Peginterferon Alfa-2a and Ribavirin in Treatment-naive Genotype 1 HCV Patients Treated for 12 Weeks: ZENITH Study, SVR12 Interim Analysis." November 7, 2011.
Vertex Poster Presentations
1. #943: "Projections Using Decision-Analytic Modeling of Long-Term Clinical Value of Telaprevir for the Treatment of HCV Patients who had Failed Prior Peginterferon/Ribavirin Treatment." November 6, 2011.
2. #1328: "Summary of Clinical Virology Findings from Clinical Trials of Telaprevir." November 7, 2011.
3. #1331: "Different likelihood of achieving SVR on a telaprevir-containing regimen among null responders, partial responders and relapsers irrespective of similar responses after a peginterferon/ribavirin 4-week lead-in phase: REALIZE study subanalysis." November 7, 2011.
4. #1368: "Impact of anemia and ribavirin dose reduction on SVR to a telaprevir-based regimen in patients with HCV genotype 1 and prior peginterferon/ribavirin treatment failure in the Phase III REALIZE study." November 7, 2011.
5. #1369: "Impact of insulin resistance on virologic response to a telaprevir-based regimen in patients with HCV genotype 1 and prior peginterferon/ribavirin treatment failure: post-hoc analysis of the REALIZE Phase III study." November 7, 2011.
6. #2105: "Sustained Virologic Response Rates and Viral Resistance Profiles Were Similar in Patients Treated with a Telaprevir-Based Regimen Regardless of Liver Fibrosis Stage." November 8, 2011.
About INCIVEK
INCIVEK is an oral medicine that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication. INCIVEK was approved by the U.S. Food and Drug Administration (FDA) in May 2011 and by Health Canada in August 2011 for people with genotype 1 chronic hepatitis C with compensated liver disease (some level of damage to the liver but the liver still functions), including cirrhosis (scarring of the liver). INCIVEK is approved for people who are new to treatment, and for people who were treated previously but who did not achieve a sustained viral response or viral cure (relapsers, partial responders and null responders).
INCIVEK (750 mg) is given as two 375 mg tablets three times daily for 12 weeks in combination with pegylated-interferon and ribavirin. Each monthly package of INCIVEK contains four weekly boxes that include daily blister strips. After the first 12 weeks, all patients stop receiving INCIVEK and continue treatment with pegylated-interferon and ribavirin alone for an additional 12 weeks or 36 weeks of treatment. With INCIVEK combination therapy, more than 60 percent of people treated for the first time, as well as those who relapsed after previous therapy, are expected to complete all treatment in 24 weeks. All other patients receive a total of 48 weeks of treatment.
Rash and anemia are the most serious side effects associated with INCIVEK, which led to treatment discontinuation in about 1 percent of people in clinical studies. The most common side effects reported with INCIVEK combination treatment include fatigue, itching, nausea, diarrhea, vomiting, anal or rectal problems, and taste changes.
Vertex developed telaprevir in collaboration with Tibotec BVBA and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America where it is being marketed under the brand name INCIVEK (in-SEE-veck). Through its affiliate, Janssen, Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. In September 2011, telaprevir was approved in the European Union and Switzerland. Telaprevir is known as INCIVO(R) in Europe. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries. In September 2011, telaprevir was approved in Japan and will be known as Telavic(R).
About VX-222
VX-222 is an oral medicine in development that is a non-nucleoside inhibitor of the HCV NS5B polymerase. VX-222 is being evaluated in a Phase 2 study in combination with INCIVEK and ribavirin, with and without pegylated-interferon. Vertex retains worldwide commercial rights to VX-222.
IMPORTANT SAFETY INFORMATION
Indication
INCIVEK(TM) (telaprevir) is a prescription medicine used with the medicines peginterferon alfa and ribavirin to treat chronic (lasting a long time) hepatitis C genotype 1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatment. It is not known if INCIVEK is safe and effective in children under 18 years of age.
Important Safety Information
INCIVEK should always be taken in combination with peginterferon alfa and ribavirin. Ribavirin may cause birth defects or death of an unborn baby. Therefore, a patient should not take INCIVEK combination treatment if she is pregnant or may become pregnant, or if he is a man with a sexual partner who is pregnant. Patients must use two forms of effective birth control during treatment and for the 6 months after treatment with these medicines.
INCIVEK and other medicines can affect each other and can also cause side effects that can be serious or life threatening. There are certain medicines patients cannot take with INCIVEK combination treatment. Patients should tell their healthcare providers about all the medicines they take, including prescription and non-prescription medicines, vitamins and herbal supplements.
INCIVEK can cause serious side effects including rash and anemia. The most common side effects of INCIVEK include itching, nausea, diarrhea, vomiting, anal or rectal problems, taste changes and tiredness. There are other possible side effects of INCIVEK, and side effects associated with peginterferon alfa and ribavirin also apply to INCIVEK combination treatment. Patients should tell their healthcare providers about any side effect that bothers them or doesn't go away.
Please see full Prescribing Information for INCIVEK including the Medication Guide, available at www.INCIVEK.com .
INCIVEK(TM) is a trademark of Vertex Pharmaceuticals Incorporated.
PEGASYS(R) and COPEGUS(R) are registered trademarks of Hoffmann-La Roche.
About Hepatitis C
Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.(1) Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.(1)Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.(1)
Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured.(2) However, approximately 60 percent of people do not achieve SVR,(3,4,5)or viral cure,(6) after treatment with 48 weeks of pegylated-interferon and ribavirin alone. If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.(7,8)
More than 170 million people worldwide are chronically infected with hepatitis C.(6) In the United States, nearly 4 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.(9)Hepatitis C is four times more prevalent in the United States compared to HIV.(9)The majority of people with hepatitis C in the United States were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.(10)Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 4,600 to 12,000 deaths annually.(11,12)By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.(9)
Special Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including statements regarding Vertex's aim to further improve treatment for hepatitis C by exploring the use of INCIVEK among those in critical need of more effective medicines and evaluating combinations that may offer higher cure rates and shorter treatment times. While the company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, future scientific, clinical, competitive or other market factors may adversely affect the potential for INCIVEK-based therapies and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through Vertex's website at www.vrtx.com . Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
About Vertex
Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.
Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, epilepsy and other life-threatening diseases.
Founded more than 20 years ago in Cambridge, MA, we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada.
(VRTX-GEN)
(1) Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf . Accessed March 21, 2011.
(2) Pearlman BL and Traub N. Sustained Virologic Response to Antiviral Therapy for Chronic Hepatitis C Virus Infection: A Cure and So Much More. Clin Infect Dis. 2011 Apr;52(7):889-900.
(3) Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.
(4) Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.
(5) McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.
(6) Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.
(7) Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).
(8) Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.
(9) Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. Available at: http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx . Updated January 11, 2010. Accessed March 21, 2011.
(10) Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease. Available at: http://www.natap.org/2009/HCV/051809_01.htm . Updated May 2009. Accessed March 21, 2011. This report was commissioned by Vertex Pharmaceuticals, Inc.
(11) Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.
(12) Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138:513-521.
SOURCE: Vertex Pharmaceuticals Incorporated
Vertex Pharmaceuticals Incorporated
Media:
Dawn Kalmar, 617-444-6992
mediainfo@vrtx.com
or
Investors:
Michael Partridge, 617-444-6108
or
Lora Pike, 617-444-6755
or
Matthew Osborne, 617-444-6057
or
Patient Inquiries: 1-855-837-8394
- Late-Breaker Presentations Include Phase 2 Data from INCIVEK-Based Combination Regimen in HIV/HCV Co-Infection and Short Duration Treatment with a Four-Drug Regimen Including INCIVEK and VX-222 -
CAMBRIDGE, Mass., Sep 30, 2011 (BUSINESS WIRE) -- Vertex Pharmaceuticals Incorporated VRTX +4.67% today announced that abstracts from its hepatitis C program, including two late-breaking posters from studies of INCIVEK(TM) (telaprevir) tablets and VX-222, were accepted for presentation at The Liver Meeting(R), the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco, November 4-8, 2011.
New data, including sustained viral response (SVR, or viral cure) results, from a Phase 2 study evaluating short durations of 12- and 24-week regimens of VX-222 in combination with INCIVEK (in-SEE-veck), pegylated-interferon and ribavirin in people with genotype 1 chronic hepatitis C who were new to treatment will be presented for the first time. Additionally, new data from a Phase 2 study evaluating INCIVEK combination treatment in people co-infected with genotype 1 chronic hepatitis C and human immunodeficiency virus (HIV) will be presented at the meeting. All people in this study were new to hepatitis C treatment.
"INCIVEK combination therapy has successfully increased viral cure rates and shortened total treatment time for the majority of people with hepatitis C who are being treated for the first time, but we have more to do," said Peter Mueller, Ph.D., Chief Scientific Officer and Executive Vice President of Global Research and Development at Vertex. "Our ongoing research is aimed at further improving treatment for hepatitis C by exploring the use of INCIVEK among those in critical need of more effective medicines and evaluating combinations, including some without interferon, that may offer higher cure rates and shorter treatment times."
The accepted abstracts are now available on the AASLD website at https://www.aasld.org/lm2011 .
INCIVEK Oral Presentations
1. #31: "Efficacy and safety of telaprevir-based regimens in cirrhotic patients with HCV genotype 1 and prior peginterferon/ribavirin treatment failure: subanalysis of the REALIZE Phase III study." November 6, 2011, 3:00 p.m. PDT.
2. #32: "Predictors of virologic response with telaprevir-based combination treatment in HCV genotype 1-infected patients with prior peginterferon/ribavirin treatment failure: post-hoc analysis of the Phase III REALIZE study." November 6, 2011, 3:15 p.m. PDT.
3. #35: "Retreatment with telaprevir/Peg-IFN/RBV after a short exposure to telaprevir in Phase I studies: interim results from a Phase IIIb rollover trial (C219)." November 6, 2011, 4:00 p.m. PDT.
4. #248: "Follow-up of SVR Durability and Viral Resistance in Patients with Chronic Hepatitis C Treated with Telaprevir-Based Regimens: Interim Analysis of the EXTEND Study." November 8, 2011, 11:00 a.m. PDT.
Vertex Late-Breaking Poster Presentations
1. #LB-8: "Telaprevir Combination with Peginterferon Alfa-2a/Ribavirin in HCV/HIV Coinfected Patients: 24-Week Treatment Interim Analysis." November 7, 2011.
2. #LB-14: "VX-222/telaprevir in Combination with Peginterferon Alfa-2a and Ribavirin in Treatment-naive Genotype 1 HCV Patients Treated for 12 Weeks: ZENITH Study, SVR12 Interim Analysis." November 7, 2011.
Vertex Poster Presentations
1. #943: "Projections Using Decision-Analytic Modeling of Long-Term Clinical Value of Telaprevir for the Treatment of HCV Patients who had Failed Prior Peginterferon/Ribavirin Treatment." November 6, 2011.
2. #1328: "Summary of Clinical Virology Findings from Clinical Trials of Telaprevir." November 7, 2011.
3. #1331: "Different likelihood of achieving SVR on a telaprevir-containing regimen among null responders, partial responders and relapsers irrespective of similar responses after a peginterferon/ribavirin 4-week lead-in phase: REALIZE study subanalysis." November 7, 2011.
4. #1368: "Impact of anemia and ribavirin dose reduction on SVR to a telaprevir-based regimen in patients with HCV genotype 1 and prior peginterferon/ribavirin treatment failure in the Phase III REALIZE study." November 7, 2011.
5. #1369: "Impact of insulin resistance on virologic response to a telaprevir-based regimen in patients with HCV genotype 1 and prior peginterferon/ribavirin treatment failure: post-hoc analysis of the REALIZE Phase III study." November 7, 2011.
6. #2105: "Sustained Virologic Response Rates and Viral Resistance Profiles Were Similar in Patients Treated with a Telaprevir-Based Regimen Regardless of Liver Fibrosis Stage." November 8, 2011.
About INCIVEK
INCIVEK is an oral medicine that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication. INCIVEK was approved by the U.S. Food and Drug Administration (FDA) in May 2011 and by Health Canada in August 2011 for people with genotype 1 chronic hepatitis C with compensated liver disease (some level of damage to the liver but the liver still functions), including cirrhosis (scarring of the liver). INCIVEK is approved for people who are new to treatment, and for people who were treated previously but who did not achieve a sustained viral response or viral cure (relapsers, partial responders and null responders).
INCIVEK (750 mg) is given as two 375 mg tablets three times daily for 12 weeks in combination with pegylated-interferon and ribavirin. Each monthly package of INCIVEK contains four weekly boxes that include daily blister strips. After the first 12 weeks, all patients stop receiving INCIVEK and continue treatment with pegylated-interferon and ribavirin alone for an additional 12 weeks or 36 weeks of treatment. With INCIVEK combination therapy, more than 60 percent of people treated for the first time, as well as those who relapsed after previous therapy, are expected to complete all treatment in 24 weeks. All other patients receive a total of 48 weeks of treatment.
Rash and anemia are the most serious side effects associated with INCIVEK, which led to treatment discontinuation in about 1 percent of people in clinical studies. The most common side effects reported with INCIVEK combination treatment include fatigue, itching, nausea, diarrhea, vomiting, anal or rectal problems, and taste changes.
Vertex developed telaprevir in collaboration with Tibotec BVBA and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America where it is being marketed under the brand name INCIVEK (in-SEE-veck). Through its affiliate, Janssen, Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. In September 2011, telaprevir was approved in the European Union and Switzerland. Telaprevir is known as INCIVO(R) in Europe. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries. In September 2011, telaprevir was approved in Japan and will be known as Telavic(R).
About VX-222
VX-222 is an oral medicine in development that is a non-nucleoside inhibitor of the HCV NS5B polymerase. VX-222 is being evaluated in a Phase 2 study in combination with INCIVEK and ribavirin, with and without pegylated-interferon. Vertex retains worldwide commercial rights to VX-222.
IMPORTANT SAFETY INFORMATION
Indication
INCIVEK(TM) (telaprevir) is a prescription medicine used with the medicines peginterferon alfa and ribavirin to treat chronic (lasting a long time) hepatitis C genotype 1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatment. It is not known if INCIVEK is safe and effective in children under 18 years of age.
Important Safety Information
INCIVEK should always be taken in combination with peginterferon alfa and ribavirin. Ribavirin may cause birth defects or death of an unborn baby. Therefore, a patient should not take INCIVEK combination treatment if she is pregnant or may become pregnant, or if he is a man with a sexual partner who is pregnant. Patients must use two forms of effective birth control during treatment and for the 6 months after treatment with these medicines.
INCIVEK and other medicines can affect each other and can also cause side effects that can be serious or life threatening. There are certain medicines patients cannot take with INCIVEK combination treatment. Patients should tell their healthcare providers about all the medicines they take, including prescription and non-prescription medicines, vitamins and herbal supplements.
INCIVEK can cause serious side effects including rash and anemia. The most common side effects of INCIVEK include itching, nausea, diarrhea, vomiting, anal or rectal problems, taste changes and tiredness. There are other possible side effects of INCIVEK, and side effects associated with peginterferon alfa and ribavirin also apply to INCIVEK combination treatment. Patients should tell their healthcare providers about any side effect that bothers them or doesn't go away.
Please see full Prescribing Information for INCIVEK including the Medication Guide, available at www.INCIVEK.com .
INCIVEK(TM) is a trademark of Vertex Pharmaceuticals Incorporated.
PEGASYS(R) and COPEGUS(R) are registered trademarks of Hoffmann-La Roche.
About Hepatitis C
Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.(1) Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.(1)Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.(1)
Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured.(2) However, approximately 60 percent of people do not achieve SVR,(3,4,5)or viral cure,(6) after treatment with 48 weeks of pegylated-interferon and ribavirin alone. If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.(7,8)
More than 170 million people worldwide are chronically infected with hepatitis C.(6) In the United States, nearly 4 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.(9)Hepatitis C is four times more prevalent in the United States compared to HIV.(9)The majority of people with hepatitis C in the United States were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.(10)Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 4,600 to 12,000 deaths annually.(11,12)By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.(9)
Special Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including statements regarding Vertex's aim to further improve treatment for hepatitis C by exploring the use of INCIVEK among those in critical need of more effective medicines and evaluating combinations that may offer higher cure rates and shorter treatment times. While the company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, future scientific, clinical, competitive or other market factors may adversely affect the potential for INCIVEK-based therapies and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through Vertex's website at www.vrtx.com . Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
About Vertex
Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.
Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, epilepsy and other life-threatening diseases.
Founded more than 20 years ago in Cambridge, MA, we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada.
(VRTX-GEN)
(1) Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf . Accessed March 21, 2011.
(2) Pearlman BL and Traub N. Sustained Virologic Response to Antiviral Therapy for Chronic Hepatitis C Virus Infection: A Cure and So Much More. Clin Infect Dis. 2011 Apr;52(7):889-900.
(3) Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.
(4) Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.
(5) McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.
(6) Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.
(7) Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).
(8) Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.
(9) Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. Available at: http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx . Updated January 11, 2010. Accessed March 21, 2011.
(10) Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease. Available at: http://www.natap.org/2009/HCV/051809_01.htm . Updated May 2009. Accessed March 21, 2011. This report was commissioned by Vertex Pharmaceuticals, Inc.
(11) Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.
(12) Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138:513-521.
SOURCE: Vertex Pharmaceuticals Incorporated
Vertex Pharmaceuticals Incorporated
Media:
Dawn Kalmar, 617-444-6992
mediainfo@vrtx.com
or
Investors:
Michael Partridge, 617-444-6108
or
Lora Pike, 617-444-6755
or
Matthew Osborne, 617-444-6057
or
Patient Inquiries: 1-855-837-8394
Merck announces presentations and posters for upcoming AASLD meeting....
Merck Announces New Data Analyses For VICTRELIS™ (Boceprevir) Will Be Presented At The American Association For The Study Of Liver Diseases 2011 Annual Meeting
Written by TradersHuddle Staff
Friday, 30 September 2011 10:58
WHITEHOUSE STATION, N.J.-( Business Wire )-
Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that several new analyses from Phase III studies of VICTRELIS™ (boceprevir), the company’s first-in-class, oral hepatitis C virus (HCV) NS3/4A protease inhibitor will be presented at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). The meeting will be held Nov. 4-8 in San Francisco. Presentations will include results from the Phase III PROVIDE study, which evaluated the efficacy of VICTRELIS in combination with peginterferon alfa and ribavirin in adult patients with chronic HCV genotype 1 infection who had prior null response to treatment with peginterferon alfa and ribavirin alone.
More than 30 abstracts highlighting Merck medicines and investigational therapies for chronic HCV will be presented at AASLD, including four oral presentations and 14 posters for VICTRELIS. One poster has been selected as a Presidential Poster of Distinction.
New data also will be presented on the efficacy and safety of Merck's MK-5172, an investigational once-daily, second-generation oral HCV NS3/4A protease inhibitor, in patients chronically infected with HCV genotypes 1 and 3.
"Merck looks forward to sharing data with the scientific community at this year's AASLD to inform the continuing fight against chronic hepatitis C," said Roger J. Pomerantz, M.D., F.A.C.P., senior vice president, Infectious Diseases, Merck Research Laboratories.
The abstracts were published today and can be accessed on the AASLD website. For program information, please visit https://www.aasld.org.
Key presentations for VICTRELIS
Efficacy of Boceprevir in Patients with Null Responses to Peginterferon/Ribavirin:
The PROVIDE study. Vierling, J. et al. Poster 931. Sunday, Nov. 6, 8:00 a.m. – 5:30 p.m. Moscone West Convention Center Poster Hall
Treatment-Naive Black Patients Treated with Boceprevir Combined with Peginterferon Alfa-2b + Ribavirin: Results from HCV SPRINT-2. McCone, J. et al. Poster 981. Sunday, Nov. 6, 8:00 a.m. – 5:30 p.m.
Analysis of Resistance-Associated Amino Acid Variants (RAVs) in non-SVR Patients Enrolled in a Retrospective Long-Term Follow-Up Analysis of Boceprevir Phase III Clinical Studies. Barnard, R.J.O. et al. Abstract #164. Oral Presentation: Monday, Nov. 7, 3:15 - 3:30p.m., Moscone West Convention Center, Rooms 2001-2003 and 2014-2016
Genotypic and Phenotypic Correlates of Resistance in HCV Genotype 1a and 1b Infected Patients Treated with Boceprevir Plus Peginterferon Alpha and Ribavirin. Ogert, R.A. et al. Poster 927. Sunday, Nov. 6, 8:00 a.m. – 5:30 p.m. Moscone West Convention Center Poster Hall. Selected as a Presidential Poster of Distinction
Other key Merck presentations
IL28B genotype predicted for >/=1 log10 IU/mL reduction in serum HCV RNA after 4 weeks of peginterferon and ribavirin therapy: implications for the use of the lead-in strategy for DAA-based treatment regimens. Thompson, A.J. et al. Abstract #157. Oral Presentation: Monday, Nov. 7, 3:00 -3:15 p.m., Moscone West Convention Center, Rooms 2006-2008
Safety and Antiviral Activity of MK-5172, a Next Generation HCV NS3/4A Protease Inhibitor with a Broad HCV Genotypic Activity Spectrum and Potent Activity Against Known Resistance Mutants, in Genotype 1 and 3 HCV-Infected Patients. Petry, A. et al. Poster 346. Saturday, Nov. 5, 2:00 p.m. – 7:30 p.m. Moscone West Convention Center Poster Hall
MK-5172, a Second-Generation HCV NS3/4A Protease Inhibitor, is Active against Common Resistance Associated Variants (RAVs) and Exhibits Cross-Genotype Activity. Graham, D. et al. Poster 370. Saturday, Nov. 5, 2:00 p.m. – 7:30 p.m. Moscone West Convention Center Poster Hall
Indications and usage for VICTRELIS
VICTRELIS was approved by the U.S. Food and Drug Administration (FDA) on May 13 for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin, in adult patients (18 years of age and older) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy.
The following points should be considered when initiating VICTRELIS for treatment of chronic hepatitis C infection:
VICTRELIS must not be used as monotherapy and should only be used in combination with peginterferon alfa and ribavirin.
VICTRELIS efficacy has not been studied in patients who have previously failed therapy with a treatment regimen that includes VICTRELIS or other HCV NS3/4A protease inhibitors. VICTRELIS in combination with peginterferon alfa and ribavirin has not been studied in patients documented to be historical null responders (less than a 2 log HCV-RNA decline by treatment week 12) during prior therapy with peginterferon alfa and ribavirin. The clinical studies included patients who were poorly interferon responsive. Patients with less than 0.5 log HCV-RNA decline in viral load at treatment week 4 with peginterferon alfa plus ribavirin alone are predicted to have a null response (less than a 2 log HCV-RNA decline by treatment week 12) to peginterferon alfa and ribavirin therapy.
Poorly interferon responsive patients who were treated with VICTRELIS in combination with peginterferon alfa and ribavirin have a lower likelihood of achieving a sustained virologic response (SVR), and a higher rate of detection of resistance-associated substitutions upon treatment failure, compared to patients with a greater response to peginterferon alfa and ribavirin.
Important safety information about VICTRELIS
All contraindications to peginterferon alfa and ribavirin also apply since VICTRELIS must be administered with peginterferon alfa and ribavirin. Because ribavirin may cause birth defects and fetal death, VICTRELIS in combination with peginterferon alfa and ribavirin is contraindicated in pregnant women and in men whose female partners are pregnant. Avoid pregnancy in female patients and female partners of male patients. Patients must have a negative pregnancy test prior to therapy; have monthly pregnancy tests; and use two or more forms of effective contraception, including intrauterine devices and barrier methods, during treatment and for at least 6 months after treatment has concluded. Systemic hormonal contraceptives may not be as effective in women while taking VICTRELIS.
VICTRELIS is contraindicated in coadministration with drugs that are highly dependent on CYP3A4/5 for clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening events. VICTRELIS also is contraindicated in coadministration with potent CYP3A4/5 inducers where significantly reduced boceprevir plasma concentrations may be associated with reduced efficacy. Drugs that are contraindicated with VICTRELIS include: alfuzosin, carbamazepine, phenobarbital, phenytoin, rifampin, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, St. John's Wort (hypericum perforatum), lovastatin, simvastatin, drosperinone, Revatio® (sildenafil) or Adcirca® (tadalafil) (when used for the treatment of pulmonary arterial hypertension), pimozide, triazolam, and midazolam (orally administered).
Anemia has been reported with peginterferon alfa and ribavirin therapy. The addition of VICTRELIS to peginterferon alfa and ribavirin is associated with an additional decrease in hemoglobin concentrations. The addition of VICTRELIS may result in a worsening of neutropenia associated with peginterferon alfa and ribavirin alone. Complete blood counts should be obtained pretreatment, and at treatment weeks 4, 8 and 12, and should be monitored closely at other time points, as clinically appropriate. If a patient has a serious adverse reaction potentially related to peginterferon alfa and ribavirin therapy, the peginterferon alfa and/or ribavirin dose should be reduced or discontinued. VICTRELIS must not be administered in the absence of peginterferon alfa and ribavirin. Dose reduction of VICTRELIS is not recommended.
The most commonly reported adverse reactions (greater than 35 percent) in clinical trials in adult patients receiving the combination of VICTRELIS with peginterferon alfa-2b and ribavirin were fatigue, anemia, nausea, headache and dysgeusia. Of these commonly reported adverse reactions, fatigue, anemia, nausea, and dysgeusia occurred at rates greater than or equal to 5 percent above the rates for peginterferon alfa and ribavirin alone in either clinical study. The incidence of these adverse reactions in previously untreated patients who received VICTRELIS combination therapy compared with peginterferon and ribavirin alone were: fatigue (58 vs. 59 percent), anemia (50 vs. 30 percent), nausea (46 vs. 42 percent), dysgeusia (35 vs. 16 percent), respectively. The incidence of these adverse reactions in previously treated patients who received VICTRELIS combination therapy compared with peginterferon and ribavirin alone were: fatigue (55 vs. 50 percent), anemia (45 vs. 20 percent), nausea (43 vs. 38 percent), dysgeusia (44 vs. 11 percent), respectively.
VICTRELIS is a strong inhibitor of CYP3A4/5 and is partly metabolized by CYP3A4/5. The potential for drug-drug interactions must be considered prior to and during therapy.
Please see U.S. prescribing information at: http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf.
Merck's global commitment to advancing hepatitis therapy
Merck is committed to building on its strong legacy in the field of viral hepatitis by continuing to discover, develop and deliver vaccines and medicines to help prevent and treat viral hepatitis. In hepatitis C, company researchers developed the first approved therapy for chronic HCV in 1991 and the first combination therapy in 1998. In addition to ongoing studies with VICTRELIS, extensive research efforts are underway to develop additional innovative oral therapies for viral hepatitis treatment.
About Merck
Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.
Forward-Looking Statement
This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Such statements may include, but are not limited to, statements about the benefits of the merger between Merck and Schering-Plough, including future financial and operating results, the combined company’s plans, objectives, expectations and intentions and other statements that are not historical facts. Such statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. Actual results may differ from those set forth in the forward-looking statements.
The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period; the impact of pharmaceutical industry regulation and health care legislation; the risk that the businesses will not be integrated successfully; disruption from the merger making it more difficult to maintain business and operational relationships; Merck’s ability to accurately predict future market conditions; dependence on the effectiveness of Merck’s patents and other protections for innovative products; the risk of new and changing regulation and health policies in the U.S. and internationally and the exposure to litigation and/or regulatory actions.
Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2010 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
Please see Prescribing Information for VICTRELIS at http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf and Medication Guide for VICTRELIS at http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_mg.pdf.
Merck & Co., Inc.Media:Pamela Eisele, 908-423-5042orLainie Keller, 908-423-4187orInvestor:Carol Ferguson, 908-423-4465
Written by TradersHuddle Staff
Friday, 30 September 2011 10:58
WHITEHOUSE STATION, N.J.-( Business Wire )-
Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that several new analyses from Phase III studies of VICTRELIS™ (boceprevir), the company’s first-in-class, oral hepatitis C virus (HCV) NS3/4A protease inhibitor will be presented at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). The meeting will be held Nov. 4-8 in San Francisco. Presentations will include results from the Phase III PROVIDE study, which evaluated the efficacy of VICTRELIS in combination with peginterferon alfa and ribavirin in adult patients with chronic HCV genotype 1 infection who had prior null response to treatment with peginterferon alfa and ribavirin alone.
More than 30 abstracts highlighting Merck medicines and investigational therapies for chronic HCV will be presented at AASLD, including four oral presentations and 14 posters for VICTRELIS. One poster has been selected as a Presidential Poster of Distinction.
New data also will be presented on the efficacy and safety of Merck's MK-5172, an investigational once-daily, second-generation oral HCV NS3/4A protease inhibitor, in patients chronically infected with HCV genotypes 1 and 3.
"Merck looks forward to sharing data with the scientific community at this year's AASLD to inform the continuing fight against chronic hepatitis C," said Roger J. Pomerantz, M.D., F.A.C.P., senior vice president, Infectious Diseases, Merck Research Laboratories.
The abstracts were published today and can be accessed on the AASLD website. For program information, please visit https://www.aasld.org.
Key presentations for VICTRELIS
Efficacy of Boceprevir in Patients with Null Responses to Peginterferon/Ribavirin:
The PROVIDE study. Vierling, J. et al. Poster 931. Sunday, Nov. 6, 8:00 a.m. – 5:30 p.m. Moscone West Convention Center Poster Hall
Treatment-Naive Black Patients Treated with Boceprevir Combined with Peginterferon Alfa-2b + Ribavirin: Results from HCV SPRINT-2. McCone, J. et al. Poster 981. Sunday, Nov. 6, 8:00 a.m. – 5:30 p.m.
Analysis of Resistance-Associated Amino Acid Variants (RAVs) in non-SVR Patients Enrolled in a Retrospective Long-Term Follow-Up Analysis of Boceprevir Phase III Clinical Studies. Barnard, R.J.O. et al. Abstract #164. Oral Presentation: Monday, Nov. 7, 3:15 - 3:30p.m., Moscone West Convention Center, Rooms 2001-2003 and 2014-2016
Genotypic and Phenotypic Correlates of Resistance in HCV Genotype 1a and 1b Infected Patients Treated with Boceprevir Plus Peginterferon Alpha and Ribavirin. Ogert, R.A. et al. Poster 927. Sunday, Nov. 6, 8:00 a.m. – 5:30 p.m. Moscone West Convention Center Poster Hall. Selected as a Presidential Poster of Distinction
Other key Merck presentations
IL28B genotype predicted for >/=1 log10 IU/mL reduction in serum HCV RNA after 4 weeks of peginterferon and ribavirin therapy: implications for the use of the lead-in strategy for DAA-based treatment regimens. Thompson, A.J. et al. Abstract #157. Oral Presentation: Monday, Nov. 7, 3:00 -3:15 p.m., Moscone West Convention Center, Rooms 2006-2008
Safety and Antiviral Activity of MK-5172, a Next Generation HCV NS3/4A Protease Inhibitor with a Broad HCV Genotypic Activity Spectrum and Potent Activity Against Known Resistance Mutants, in Genotype 1 and 3 HCV-Infected Patients. Petry, A. et al. Poster 346. Saturday, Nov. 5, 2:00 p.m. – 7:30 p.m. Moscone West Convention Center Poster Hall
MK-5172, a Second-Generation HCV NS3/4A Protease Inhibitor, is Active against Common Resistance Associated Variants (RAVs) and Exhibits Cross-Genotype Activity. Graham, D. et al. Poster 370. Saturday, Nov. 5, 2:00 p.m. – 7:30 p.m. Moscone West Convention Center Poster Hall
Indications and usage for VICTRELIS
VICTRELIS was approved by the U.S. Food and Drug Administration (FDA) on May 13 for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin, in adult patients (18 years of age and older) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy.
The following points should be considered when initiating VICTRELIS for treatment of chronic hepatitis C infection:
VICTRELIS must not be used as monotherapy and should only be used in combination with peginterferon alfa and ribavirin.
VICTRELIS efficacy has not been studied in patients who have previously failed therapy with a treatment regimen that includes VICTRELIS or other HCV NS3/4A protease inhibitors. VICTRELIS in combination with peginterferon alfa and ribavirin has not been studied in patients documented to be historical null responders (less than a 2 log HCV-RNA decline by treatment week 12) during prior therapy with peginterferon alfa and ribavirin. The clinical studies included patients who were poorly interferon responsive. Patients with less than 0.5 log HCV-RNA decline in viral load at treatment week 4 with peginterferon alfa plus ribavirin alone are predicted to have a null response (less than a 2 log HCV-RNA decline by treatment week 12) to peginterferon alfa and ribavirin therapy.
Poorly interferon responsive patients who were treated with VICTRELIS in combination with peginterferon alfa and ribavirin have a lower likelihood of achieving a sustained virologic response (SVR), and a higher rate of detection of resistance-associated substitutions upon treatment failure, compared to patients with a greater response to peginterferon alfa and ribavirin.
Important safety information about VICTRELIS
All contraindications to peginterferon alfa and ribavirin also apply since VICTRELIS must be administered with peginterferon alfa and ribavirin. Because ribavirin may cause birth defects and fetal death, VICTRELIS in combination with peginterferon alfa and ribavirin is contraindicated in pregnant women and in men whose female partners are pregnant. Avoid pregnancy in female patients and female partners of male patients. Patients must have a negative pregnancy test prior to therapy; have monthly pregnancy tests; and use two or more forms of effective contraception, including intrauterine devices and barrier methods, during treatment and for at least 6 months after treatment has concluded. Systemic hormonal contraceptives may not be as effective in women while taking VICTRELIS.
VICTRELIS is contraindicated in coadministration with drugs that are highly dependent on CYP3A4/5 for clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening events. VICTRELIS also is contraindicated in coadministration with potent CYP3A4/5 inducers where significantly reduced boceprevir plasma concentrations may be associated with reduced efficacy. Drugs that are contraindicated with VICTRELIS include: alfuzosin, carbamazepine, phenobarbital, phenytoin, rifampin, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, St. John's Wort (hypericum perforatum), lovastatin, simvastatin, drosperinone, Revatio® (sildenafil) or Adcirca® (tadalafil) (when used for the treatment of pulmonary arterial hypertension), pimozide, triazolam, and midazolam (orally administered).
Anemia has been reported with peginterferon alfa and ribavirin therapy. The addition of VICTRELIS to peginterferon alfa and ribavirin is associated with an additional decrease in hemoglobin concentrations. The addition of VICTRELIS may result in a worsening of neutropenia associated with peginterferon alfa and ribavirin alone. Complete blood counts should be obtained pretreatment, and at treatment weeks 4, 8 and 12, and should be monitored closely at other time points, as clinically appropriate. If a patient has a serious adverse reaction potentially related to peginterferon alfa and ribavirin therapy, the peginterferon alfa and/or ribavirin dose should be reduced or discontinued. VICTRELIS must not be administered in the absence of peginterferon alfa and ribavirin. Dose reduction of VICTRELIS is not recommended.
The most commonly reported adverse reactions (greater than 35 percent) in clinical trials in adult patients receiving the combination of VICTRELIS with peginterferon alfa-2b and ribavirin were fatigue, anemia, nausea, headache and dysgeusia. Of these commonly reported adverse reactions, fatigue, anemia, nausea, and dysgeusia occurred at rates greater than or equal to 5 percent above the rates for peginterferon alfa and ribavirin alone in either clinical study. The incidence of these adverse reactions in previously untreated patients who received VICTRELIS combination therapy compared with peginterferon and ribavirin alone were: fatigue (58 vs. 59 percent), anemia (50 vs. 30 percent), nausea (46 vs. 42 percent), dysgeusia (35 vs. 16 percent), respectively. The incidence of these adverse reactions in previously treated patients who received VICTRELIS combination therapy compared with peginterferon and ribavirin alone were: fatigue (55 vs. 50 percent), anemia (45 vs. 20 percent), nausea (43 vs. 38 percent), dysgeusia (44 vs. 11 percent), respectively.
VICTRELIS is a strong inhibitor of CYP3A4/5 and is partly metabolized by CYP3A4/5. The potential for drug-drug interactions must be considered prior to and during therapy.
Please see U.S. prescribing information at: http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf.
Merck's global commitment to advancing hepatitis therapy
Merck is committed to building on its strong legacy in the field of viral hepatitis by continuing to discover, develop and deliver vaccines and medicines to help prevent and treat viral hepatitis. In hepatitis C, company researchers developed the first approved therapy for chronic HCV in 1991 and the first combination therapy in 1998. In addition to ongoing studies with VICTRELIS, extensive research efforts are underway to develop additional innovative oral therapies for viral hepatitis treatment.
About Merck
Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.
Forward-Looking Statement
This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Such statements may include, but are not limited to, statements about the benefits of the merger between Merck and Schering-Plough, including future financial and operating results, the combined company’s plans, objectives, expectations and intentions and other statements that are not historical facts. Such statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. Actual results may differ from those set forth in the forward-looking statements.
The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period; the impact of pharmaceutical industry regulation and health care legislation; the risk that the businesses will not be integrated successfully; disruption from the merger making it more difficult to maintain business and operational relationships; Merck’s ability to accurately predict future market conditions; dependence on the effectiveness of Merck’s patents and other protections for innovative products; the risk of new and changing regulation and health policies in the U.S. and internationally and the exposure to litigation and/or regulatory actions.
Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2010 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
Please see Prescribing Information for VICTRELIS at http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf and Medication Guide for VICTRELIS at http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_mg.pdf.
Merck & Co., Inc.Media:Pamela Eisele, 908-423-5042orLainie Keller, 908-423-4187orInvestor:Carol Ferguson, 908-423-4465
Wednesday, September 28, 2011
Updated Hepatitis C Practice Guidelines Now Available from AASLD
Short version - new AASLD HCV Practice Guidelines are now available here
Updated Hepatitis C Practice Guidelines Now Available from AASLD
ARLINGTON, Va., Sept. 28, 2011 /PRNewswire via COMTEX/ -- On Monday, September 26, 2011, the American Association for the Study of Liver Diseases published online at its journal Hepatology's website ( http://onlinelibrary.wiley.com/doi/10.1002/hep.24641/full ) an update to its practice guidelines for hepatitis C - "An Update on Treatment of Genotype 1 Chronic Hepatitis C Virus Infection: 2011 Practice Guideline by the American Association for the Study of Liver Diseases." AASLD is the premiere organization for research and education in the area of liver disease. The authors of the update are Marc Ghany, David R. Nelson, Doris B. Strader, David L. Thomas, and Leonard B. Seeff, all of whom are thought leaders in the field of hepatology.
The guidelines are noteworthy because they address treatment of patients with hepatitis C using two recently FDA approved drugs - telaprevir and boceprevir. Both long-awaited drugs were approved by the FDA in May 2011, are direct acting antivirals (DAA), and improve cure rates for patients with hepatitis C genotype 1. In addition, both drugs are in the forefront of a wave of new drugs that will reach the market in the near future. According to AASLD President T. Jake Liang, MD, "The AASLD has been very proactive in modifying our HCV guidelines to reflect this change. Ever since we knew of the improved treatment response with the addition of DAAs, the AASLD Practice Guideline Committee has moved quickly to update the existing guideline. Just 4 months after the official approval of the first two DAAs, the updated guideline is available on the website of our journal Hepatology."
DAAs promise great hope, but AASLD has expedited the writing and review of its practice guideline because those drugs do require a level of expertise for practitioners if optimum outcomes can be reached. In addition, treatment schedules will be complex and different for each DAA. The newly approved treatment schedules have more side effects than pegylated interferon and ribavirin, and should be managed carefully. The drugs are intended for use only in combination with pegylated interfreron and ribavirin, and if not used in combination with those drugs, treatment will be ineffective and will cause emergence of antiviral-resistant mutants that could be difficult to treat subsequently.
Dr. Liang said, "The DAAs will likely change the landscape of treatment for hepatitis C. However a note of caution is necessary to remind all of us that the treatment regimens are complicated and different. They are associated with more side effects than the standard peginterferon and ribavirin combination, and therefore need careful management."
Some of the concerns noted by AASLD are:
They are only approved for use in patients with HCV genotype 1.
They are not approved for use in post-transplant recurrent HCV.
They are not approved for use in HIV/HCV coinfected patients.
They are not approved for use in children.
Gary Davis, MD, Chair of AASLD's special interest group on hepatitis C acknowledges the complexities the new DAAs pose, but is still optimistic about these recent developments and the promise of new drugs. Dr. Davis said, "Hepatologists, gastroenterologists, and others who treat patients with chronic hepatitis C now have the option of two newly approved drugs that directly interfere with the ability of the hepatitis C virus to persist in the patient. Administration of these drugs is not straight-forward and increases the complexities of patient management. The new AASLD guidelines review how and when to use these agents in the clinic. This timely document should be a great asset in the management of our patients with hepatitis C."
Dr. Liang echoes those sentiments, adding, "The approval of DAAs for treatment of hepatitis C reflects an important milestone in our efforts to combat the global public health burden of viral hepatitis."
About the American Association for the Study of Liver Diseases
AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. Visit our website at aasld.org.
Media Contact: Gregory Bologna703/299-9766gbologna@aasld.org
SOURCE American Association for the Study of Liver Diseases (AASLD)
Copyright (C) 2011 PR Newswire. All rights reserved
Updated Hepatitis C Practice Guidelines Now Available from AASLD
ARLINGTON, Va., Sept. 28, 2011 /PRNewswire via COMTEX/ -- On Monday, September 26, 2011, the American Association for the Study of Liver Diseases published online at its journal Hepatology's website ( http://onlinelibrary.wiley.com/doi/10.1002/hep.24641/full ) an update to its practice guidelines for hepatitis C - "An Update on Treatment of Genotype 1 Chronic Hepatitis C Virus Infection: 2011 Practice Guideline by the American Association for the Study of Liver Diseases." AASLD is the premiere organization for research and education in the area of liver disease. The authors of the update are Marc Ghany, David R. Nelson, Doris B. Strader, David L. Thomas, and Leonard B. Seeff, all of whom are thought leaders in the field of hepatology.
The guidelines are noteworthy because they address treatment of patients with hepatitis C using two recently FDA approved drugs - telaprevir and boceprevir. Both long-awaited drugs were approved by the FDA in May 2011, are direct acting antivirals (DAA), and improve cure rates for patients with hepatitis C genotype 1. In addition, both drugs are in the forefront of a wave of new drugs that will reach the market in the near future. According to AASLD President T. Jake Liang, MD, "The AASLD has been very proactive in modifying our HCV guidelines to reflect this change. Ever since we knew of the improved treatment response with the addition of DAAs, the AASLD Practice Guideline Committee has moved quickly to update the existing guideline. Just 4 months after the official approval of the first two DAAs, the updated guideline is available on the website of our journal Hepatology."
DAAs promise great hope, but AASLD has expedited the writing and review of its practice guideline because those drugs do require a level of expertise for practitioners if optimum outcomes can be reached. In addition, treatment schedules will be complex and different for each DAA. The newly approved treatment schedules have more side effects than pegylated interferon and ribavirin, and should be managed carefully. The drugs are intended for use only in combination with pegylated interfreron and ribavirin, and if not used in combination with those drugs, treatment will be ineffective and will cause emergence of antiviral-resistant mutants that could be difficult to treat subsequently.
Dr. Liang said, "The DAAs will likely change the landscape of treatment for hepatitis C. However a note of caution is necessary to remind all of us that the treatment regimens are complicated and different. They are associated with more side effects than the standard peginterferon and ribavirin combination, and therefore need careful management."
Some of the concerns noted by AASLD are:
They are only approved for use in patients with HCV genotype 1.
They are not approved for use in post-transplant recurrent HCV.
They are not approved for use in HIV/HCV coinfected patients.
They are not approved for use in children.
Gary Davis, MD, Chair of AASLD's special interest group on hepatitis C acknowledges the complexities the new DAAs pose, but is still optimistic about these recent developments and the promise of new drugs. Dr. Davis said, "Hepatologists, gastroenterologists, and others who treat patients with chronic hepatitis C now have the option of two newly approved drugs that directly interfere with the ability of the hepatitis C virus to persist in the patient. Administration of these drugs is not straight-forward and increases the complexities of patient management. The new AASLD guidelines review how and when to use these agents in the clinic. This timely document should be a great asset in the management of our patients with hepatitis C."
Dr. Liang echoes those sentiments, adding, "The approval of DAAs for treatment of hepatitis C reflects an important milestone in our efforts to combat the global public health burden of viral hepatitis."
About the American Association for the Study of Liver Diseases
AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. Visit our website at aasld.org.
Media Contact: Gregory Bologna703/299-9766gbologna@aasld.org
SOURCE American Association for the Study of Liver Diseases (AASLD)
Copyright (C) 2011 PR Newswire. All rights reserved
Tuesday, November 16, 2010
Zobair M. Younossi, MD discusses "A New Era of Hepatitis C Therapy"
Zobair M. Younossi, MD, the Executive Director of the Center for Liver Diseases and Vice President of Research at the Inova Health System in Falls Church, Virginia discusses the STAT-C drugs and other novel therapies for Hepatitis C from AASLD 2010. Features a video and transcript. Watch and read here.
Tuesday, November 2, 2010
Biolex presents positive tolerability data of Locteron vs Peg-Intron at AASLD...
Market Wire - Nov. 01, 2010
PITTSBORO, NC -- (MARKET WIRE) -- 11/01/10 -- Biolex Therapeutics, Inc. today announced positive results from two Phase 2b trials further demonstrating the strong anti-viral response and tolerability advantages of the 480 µg dose of Locteron® in the treatment of hepatitis C. In the Phase 2b trials, patients directly reported flu-like adverse events on a daily basis through an electronic patient-reported outcome (ePRO) system, and the results demonstrated a statistically significant reduction in the frequency and severity of flu-like adverse events and reduced use of concomitant (analgesic/antipyretic) medications for patients treated with Locteron compared to patients treated with the PEG-Intron® control. Locteron, controlled-release interferon alpha 2b, is designed to offer key advantages compared to currently marketed interferons as a core component of combination therapies for the treatment of hepatitis C. These advantages include reduced flu-like symptoms, reduced rates of depression, and a less frequent dosing regimen with half the number of injections. The "EMPOWER" Phase 2b ePRO results will be presented today in a late-breaker session at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston.
EMPOWER is a prospectively designed analysis of the combined results from two Phase 2b hepatitis C trials focusing on the 480 µg dose of Locteron (the middle dose of three Locteron doses evaluated in the two trials). Through 12 weeks of treatment, 50% of the patients in the Locteron 480 µg group achieved cEVR (undetectable HCV RNA) compared to 46% of the patients in the PEG-Intron group. As a result of its controlled-release mechanism, Locteron achieved strong efficacy results while being dosed half as frequently as PEG-Intron.
The AASLD presentation today includes for the first time results from the ePRO adverse-event reporting system where patients directly recorded their flu-like adverse events on a daily basis, providing greater insight into the patients' real world experiences with these side effects and the impact on their daily activities. In addition to the self-reporting by patients with the ePRO system, flu-like adverse events were also recorded using traditional weekly adverse event assessments performed by the clinical sites. Flu-like adverse events were predefined to include arthralgia, chills, fever, headache, and myalgia.
A substantial reduction in flu-like adverse events for patients treated with Locteron compared to PEG-Intron was evident even in the first week after initiation of treatment and continued through the 12-week time point through which the ePRO system was utilized. The reduction in flu-like adverse events during the week after the first injection supports the hypothesis that the slower rise to Cmax provided by the controlled-release mechanism of Locteron contributes to the tolerability advantages seen in multiple clinical trials. A comparison of the flu-like adverse event reporting by the clinical sites and by ePRO provide independent confirmation of the substantial benefits Locteron provided in reducing these side effects as outlined in the table below:
Locteron Reduction in Flu-Like Adverse Events (Week 1)
---------------------------------------------------------
Total Events Moderate and Severe Events
---------------------------- ----------------------------
Clinical Site Patient (ePRO) Clinical Site Patient (ePRO)
Reporting Self-Reporting Reporting Self-Reporting
------------- -------------- ------------- --------------
Locteron Reduction 50% 51% 70% 39%
In Flu-Like Adverse Reduction Reduction Reduction Reduction
Events Compared to
PEG-Intron
"The ePRO results being presented for the first time today are robust and provide important insight into the impact that flu-like adverse events have on patients' daily lives," said Patrick Marcellin, MD, PhD, Professor of Hepatology at the University of Paris and Head of the Viral Hepatitis Research Unit in Hôpital Beaujon, Clichy. "Treatment of hepatitis C is likely to progress to triple and quad therapies in which interferons are combined with one or more direct-acting anti-viral drugs. Locteron's advantages with regards to flu-like adverse events, depression and dosing frequency have the potential to enhance the overall tolerability of, and patient adherence to, these future combinations."
Consistent with the reduction in flu-like adverse events, less than half as many Locteron patients used concomitant medications (analgesics and antipyretics) compared to the usage of these medications by PEG-Intron patients during the study period as detailed below.
Percentage of Patients Using
Concomitant Medications
-----------------------------------------
Locteron
480 µg PEG-Intron
-------------------- --------------------
Patients Using Analgesics 27% 59%
Patients Using Antipyretics 23% 49%
A comparison of the ePRO and clinic site reporting highlights the fact that flu-like adverse events may even be more important to patients than historically believed. The total flu-like adverse events reported directly by the patients using the ePRO system during the first 12 weeks of EMPOWER was more than four times greater than the total flu-like adverse events recorded by the clinical sites. Also of importance, patients rated 80% of their flu-like adverse events as moderate or severe in their ePRO reports, compared to the clinical site reporting in which only 13% of flu-like adverse events were rated as moderate or severe. Despite the apparent differences in sensitivity in the two adverse event reporting methods, the results from both the ePRO and weekly clinic visits independently confirm the reduction in flu-like adverse events for patients treated with Locteron compared to patients treated with PEG-Intron. Through the 12-weeks, the difference in flu-like adverse event counts was statistically significant when measured by both the ePRO and clinical site reporting methods (p < 0.001 for each).
The relevance of flu-like adverse events was highlighted in a survey of hepatitis C patients published in the Journal of Viral Hepatitis in June 2010 in which depression and flu-like symptoms were cited as the two most important adverse events impacting patient adherence to treatment. Last week Biolex reported 48-week results from its SELECT-2 Phase 2b trial of Locteron demonstrating substantial reductions in depression compared to PEG-Intron.
AASLD Presentation
The EMPOWER ePRO and clinical-site tolerability results will be presented today by the lead author, Walker Long, MD, Chief Medical Officer and Vice President, Drug Development, Biolex Therapeutics, in the form of a poster titled "Adverse Event Reporting During HCV Treatment Via Weekly Clinic Visits Substantially Underestimates Flu Frequency & Severity Compared to Daily ePRO: Results From 133 Patients in EMPOWER."
"The EMPOWER results are notable in that they show a statistically significant reduction of flu-like adverse events for Locteron confirmed by two sources, the clinical site assessments and the daily patient reporting of side effects through the ePRO System. The reductions in the percent of patients using analgesics and in overall analgesic use observed in the Locteron group provide additional support for improved tolerability on Locteron," said Dr. Long. "These results complement the positive results released last week from our SELECT-2 Phase 2b trial in which we showed statistically significant reductions in flu-like adverse events for three different Locteron doses, and substantial reductions in depression for the Locteron 480 and 320 µg doses."
About EMPOWER Study
The objective of the EMPOWER study was to test the hypothesis that the 480 µg dose of Locteron dosed once every two weeks reduces flu-like symptoms but retains equivalent efficacy compared to PEG-Intron (1.5 µg/kg, administered every week). The 133 patients in the EMPOWER study were enrolled in two contributing Phase 2b trials:
* SELECT-2, a Phase 2b dose-finding trial evaluating the 320, 480 or 640 µg doses of Locteron versus PEG-Intron.
* The 480 STUDY, a Phase 2b trial evaluating the 480 µg dose of Locteron versus PEG-Intron.
All patients in both trials were treatment-naïve-genotype-1 subjects with chronic hepatitis C, and all patients were also treated with weight-based ribavirin. A total of 30 sites participated in the two trials (14 sites in the US, 11 in Europe, and five in Israel).
Locteron Overview
Locteron, controlled-release interferon alpha 2b, is designed to offer key advantages compared to currently approved products, including reduced flu-like symptoms and rates of depression, and cutting in half the number of injections required. In contrast to Locteron, the currently approved products, Pegasys® and PEG-Intron, are immediate-release products that lack a controlled-release mechanism. The two-drug combination of interferon alpha and ribavirin serves as the current standard of care for the treatment of hepatitis C. The launch of the first direct-acting anti-viral (DAA) product, projected for 2011, will transform treatment of genotype-1 patients to a triple-drug therapy (interferon plus ribavirin plus DAA) and substantially raise cure rates. Other recent triple or quad drug combinations with interferon (including interferon plus ribavirin plus two DAA agents) have shown promise in early clinical testing, further solidifying the continued role of interferon in the treatment of hepatitis C. It is estimated that worldwide sales of interferon products for the treatment of hepatitis C will approach $6 billion by 2016.
Locteron incorporates an advanced controlled-release drug delivery technology that allows dosing once every two weeks, more convenient than Pegasys and PEG-Intron, each of which require dosing every week. More importantly, Locteron's controlled-release mechanism results in the gradual release of interferon alpha 2b to patients over the duration of two weeks and avoids the early peak plasma levels of the active interferon that characterize the pegylated interferons. This controlled-release mechanism is designed to reduce the frequency and severity of flu-like symptoms and depression commonly experienced by patients treated with pegylated interferons.
Locteron is an investigational therapeutic candidate and has not been approved for sale by the United States Food and Drug Administration or by any international regulatory agency.
PITTSBORO, NC -- (MARKET WIRE) -- 11/01/10 -- Biolex Therapeutics, Inc. today announced positive results from two Phase 2b trials further demonstrating the strong anti-viral response and tolerability advantages of the 480 µg dose of Locteron® in the treatment of hepatitis C. In the Phase 2b trials, patients directly reported flu-like adverse events on a daily basis through an electronic patient-reported outcome (ePRO) system, and the results demonstrated a statistically significant reduction in the frequency and severity of flu-like adverse events and reduced use of concomitant (analgesic/antipyretic) medications for patients treated with Locteron compared to patients treated with the PEG-Intron® control. Locteron, controlled-release interferon alpha 2b, is designed to offer key advantages compared to currently marketed interferons as a core component of combination therapies for the treatment of hepatitis C. These advantages include reduced flu-like symptoms, reduced rates of depression, and a less frequent dosing regimen with half the number of injections. The "EMPOWER" Phase 2b ePRO results will be presented today in a late-breaker session at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston.
EMPOWER is a prospectively designed analysis of the combined results from two Phase 2b hepatitis C trials focusing on the 480 µg dose of Locteron (the middle dose of three Locteron doses evaluated in the two trials). Through 12 weeks of treatment, 50% of the patients in the Locteron 480 µg group achieved cEVR (undetectable HCV RNA) compared to 46% of the patients in the PEG-Intron group. As a result of its controlled-release mechanism, Locteron achieved strong efficacy results while being dosed half as frequently as PEG-Intron.
The AASLD presentation today includes for the first time results from the ePRO adverse-event reporting system where patients directly recorded their flu-like adverse events on a daily basis, providing greater insight into the patients' real world experiences with these side effects and the impact on their daily activities. In addition to the self-reporting by patients with the ePRO system, flu-like adverse events were also recorded using traditional weekly adverse event assessments performed by the clinical sites. Flu-like adverse events were predefined to include arthralgia, chills, fever, headache, and myalgia.
A substantial reduction in flu-like adverse events for patients treated with Locteron compared to PEG-Intron was evident even in the first week after initiation of treatment and continued through the 12-week time point through which the ePRO system was utilized. The reduction in flu-like adverse events during the week after the first injection supports the hypothesis that the slower rise to Cmax provided by the controlled-release mechanism of Locteron contributes to the tolerability advantages seen in multiple clinical trials. A comparison of the flu-like adverse event reporting by the clinical sites and by ePRO provide independent confirmation of the substantial benefits Locteron provided in reducing these side effects as outlined in the table below:
Locteron Reduction in Flu-Like Adverse Events (Week 1)
---------------------------------------------------------
Total Events Moderate and Severe Events
---------------------------- ----------------------------
Clinical Site Patient (ePRO) Clinical Site Patient (ePRO)
Reporting Self-Reporting Reporting Self-Reporting
------------- -------------- ------------- --------------
Locteron Reduction 50% 51% 70% 39%
In Flu-Like Adverse Reduction Reduction Reduction Reduction
Events Compared to
PEG-Intron
"The ePRO results being presented for the first time today are robust and provide important insight into the impact that flu-like adverse events have on patients' daily lives," said Patrick Marcellin, MD, PhD, Professor of Hepatology at the University of Paris and Head of the Viral Hepatitis Research Unit in Hôpital Beaujon, Clichy. "Treatment of hepatitis C is likely to progress to triple and quad therapies in which interferons are combined with one or more direct-acting anti-viral drugs. Locteron's advantages with regards to flu-like adverse events, depression and dosing frequency have the potential to enhance the overall tolerability of, and patient adherence to, these future combinations."
Consistent with the reduction in flu-like adverse events, less than half as many Locteron patients used concomitant medications (analgesics and antipyretics) compared to the usage of these medications by PEG-Intron patients during the study period as detailed below.
Percentage of Patients Using
Concomitant Medications
-----------------------------------------
Locteron
480 µg PEG-Intron
-------------------- --------------------
Patients Using Analgesics 27% 59%
Patients Using Antipyretics 23% 49%
A comparison of the ePRO and clinic site reporting highlights the fact that flu-like adverse events may even be more important to patients than historically believed. The total flu-like adverse events reported directly by the patients using the ePRO system during the first 12 weeks of EMPOWER was more than four times greater than the total flu-like adverse events recorded by the clinical sites. Also of importance, patients rated 80% of their flu-like adverse events as moderate or severe in their ePRO reports, compared to the clinical site reporting in which only 13% of flu-like adverse events were rated as moderate or severe. Despite the apparent differences in sensitivity in the two adverse event reporting methods, the results from both the ePRO and weekly clinic visits independently confirm the reduction in flu-like adverse events for patients treated with Locteron compared to patients treated with PEG-Intron. Through the 12-weeks, the difference in flu-like adverse event counts was statistically significant when measured by both the ePRO and clinical site reporting methods (p < 0.001 for each).
The relevance of flu-like adverse events was highlighted in a survey of hepatitis C patients published in the Journal of Viral Hepatitis in June 2010 in which depression and flu-like symptoms were cited as the two most important adverse events impacting patient adherence to treatment. Last week Biolex reported 48-week results from its SELECT-2 Phase 2b trial of Locteron demonstrating substantial reductions in depression compared to PEG-Intron.
AASLD Presentation
The EMPOWER ePRO and clinical-site tolerability results will be presented today by the lead author, Walker Long, MD, Chief Medical Officer and Vice President, Drug Development, Biolex Therapeutics, in the form of a poster titled "Adverse Event Reporting During HCV Treatment Via Weekly Clinic Visits Substantially Underestimates Flu Frequency & Severity Compared to Daily ePRO: Results From 133 Patients in EMPOWER."
"The EMPOWER results are notable in that they show a statistically significant reduction of flu-like adverse events for Locteron confirmed by two sources, the clinical site assessments and the daily patient reporting of side effects through the ePRO System. The reductions in the percent of patients using analgesics and in overall analgesic use observed in the Locteron group provide additional support for improved tolerability on Locteron," said Dr. Long. "These results complement the positive results released last week from our SELECT-2 Phase 2b trial in which we showed statistically significant reductions in flu-like adverse events for three different Locteron doses, and substantial reductions in depression for the Locteron 480 and 320 µg doses."
About EMPOWER Study
The objective of the EMPOWER study was to test the hypothesis that the 480 µg dose of Locteron dosed once every two weeks reduces flu-like symptoms but retains equivalent efficacy compared to PEG-Intron (1.5 µg/kg, administered every week). The 133 patients in the EMPOWER study were enrolled in two contributing Phase 2b trials:
* SELECT-2, a Phase 2b dose-finding trial evaluating the 320, 480 or 640 µg doses of Locteron versus PEG-Intron.
* The 480 STUDY, a Phase 2b trial evaluating the 480 µg dose of Locteron versus PEG-Intron.
All patients in both trials were treatment-naïve-genotype-1 subjects with chronic hepatitis C, and all patients were also treated with weight-based ribavirin. A total of 30 sites participated in the two trials (14 sites in the US, 11 in Europe, and five in Israel).
Locteron Overview
Locteron, controlled-release interferon alpha 2b, is designed to offer key advantages compared to currently approved products, including reduced flu-like symptoms and rates of depression, and cutting in half the number of injections required. In contrast to Locteron, the currently approved products, Pegasys® and PEG-Intron, are immediate-release products that lack a controlled-release mechanism. The two-drug combination of interferon alpha and ribavirin serves as the current standard of care for the treatment of hepatitis C. The launch of the first direct-acting anti-viral (DAA) product, projected for 2011, will transform treatment of genotype-1 patients to a triple-drug therapy (interferon plus ribavirin plus DAA) and substantially raise cure rates. Other recent triple or quad drug combinations with interferon (including interferon plus ribavirin plus two DAA agents) have shown promise in early clinical testing, further solidifying the continued role of interferon in the treatment of hepatitis C. It is estimated that worldwide sales of interferon products for the treatment of hepatitis C will approach $6 billion by 2016.
Locteron incorporates an advanced controlled-release drug delivery technology that allows dosing once every two weeks, more convenient than Pegasys and PEG-Intron, each of which require dosing every week. More importantly, Locteron's controlled-release mechanism results in the gradual release of interferon alpha 2b to patients over the duration of two weeks and avoids the early peak plasma levels of the active interferon that characterize the pegylated interferons. This controlled-release mechanism is designed to reduce the frequency and severity of flu-like symptoms and depression commonly experienced by patients treated with pegylated interferons.
Locteron is an investigational therapeutic candidate and has not been approved for sale by the United States Food and Drug Administration or by any international regulatory agency.
Thursday, October 28, 2010
Pharmasset releases Phase 1 data on HCV nucleotide inhibitor PSI-938
Reports Positive Preliminary Antiviral Data with PSI-938 for the Treatment of Hepatitis C
10/28/2010
PRINCETON, N.J., Oct. 28 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS) reported positive preliminary results today from its phase I monotherapy trial of PSI-352938 ("PSI-938") for the treatment of chronic hepatitis C (HCV). PSI-938 is a guanosine nucleotide analog polymerase inhibitor in development for the treatment of chronic HCV infection.
10/28/2010
PRINCETON, N.J., Oct. 28 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS) reported positive preliminary results today from its phase I monotherapy trial of PSI-352938 ("PSI-938") for the treatment of chronic hepatitis C (HCV). PSI-938 is a guanosine nucleotide analog polymerase inhibitor in development for the treatment of chronic HCV infection.
PSI-938 Phase 1 Multiple Ascending Dose Study Overview
In August 2010, Pharmasset initiated a phase 1 multiple ascending dose study with PSI-938 administered once daily (QD) or twice daily (BID) for 7 days. The trial was conducted at two US centers as a blinded, randomized, and placebo-controlled study in 40 patients chronically infected with HCV genotype 1. The primary objective was to assess the safety, tolerability, and pharmacokinetics of PSI-938 administered over 7 days. The secondary objective was to assess antiviral activity by measuring the change in HCV RNA. Patients were randomized within each cohort to receive either PSI-938 (8 patients per cohort) or placebo (2 patients per cohort). Four dose cohorts of PSI-938 (100 mg QD, 200 mg QD, 300 mg QD and 100 mg BID) have been completed.
PSI-938 Antiviral Activity Summary
Preliminary Antiviral Response Observed Following PSI-938 Administered as Monotherapy for 7 Days | ||||||
Dose | n | Median Change in HCV RNA at Day 8 | Range | Number of Subjects with HCV RNA | ||
(log10 IU/mL) | (log10 IU/mL) | |||||
100 mg QD | 8 | -4.31 | -2.66 to -5.12 | 1 | 3 | |
200 mg QD | 8 | -4.64 | -3.49 to -5.35 | 5 | 7 | |
300 mg QD | 8 | -3.94 | -3.43 to -5.29 | 4 | 4 | |
100 mg BID | 8 | -4.59 | -3.94 to -5.08 | 2 | 3 | |
Placebo | 8 | -0.05 | +0.17 to -0.29 | 0 | 0 | |
LOD = limit of detection (<15 IU/mL) LOQ = limit of quantification (<43 IU/mL) | ||||||
PSI-938 demonstrated potent antiviral activity with a mean HCV RNA change from baseline of 4.31 log10 IU/mL, 4.64 log10 IU/mL, 3.94 log10 IU/mL and 4.59 log10 IU/mL in patients receiving 100 mg QD, 200 mg QD, 300 mg QD and 100 mg BID for seven days, respectively. HCV RNA declined consistently throughout the 7-day dosing period, with no viral breakthrough. For the 16 subjects who received PSI-938 200 mg QD or 300 mg QD for 7 days, more than half (9 of 16) of the subjects on PSI-938 monotherapy achieved HCV RNA below the limit of detection (15 IU/mL) and 11 out of 16 patients achieved HCV RNA below the limit of quantification (43 IU/mL).
PSI-938 Pharmacokinetic and Safety Summary
Pharmacokinetics parameters were similar between healthy subjects in the single ascending dose study and HCV infected patients in the seven-day multiple ascending dose study. PSI-938 at all doses provided good systemic exposure and continue to support once-daily administration.
PSI-938 was generally safe and well tolerated across all doses studied to date with no serious adverse events and no discontinuations. There were no dose-related trends in adverse events through the dose escalations, no grade 4 treatment emergent laboratory changes, and no trends in clinical laboratory abnormalities.
PSI-938 SAD and preclinical data
The Phase 1a single ascending dose study conducted earlier this year assessed single doses of PSI-938 ranging from 100 mg to 1600 mg or matching placebo in healthy male and female volunteers. No dose-limiting toxicity was identified. Safety and pharmacokinetic data supported progression of PSI-938 to the 7-day monotherapy trial. Full data from the SAD trial will be presented at the upcoming AASLD Annual Liver Meeting in Boston, MA, October 29-November 3, 2010 (poster #1890).
Preclinically, both PSI-938 and Pharmasset's other guanosine analog, PSI-661, which is in late preclinical development, have demonstrated similar potency against wild-type HCV or HCV with the S282T mutation, which can be selected by RG7128 and PSI-7977 in vitro. Although the S282T has not been detected in treatment-naive individuals with HCV, nor selected in clinical trials with any of Pharmasset's nucleoside/tide analogs, the potential for interferon-sparing regimens may increase the focus on antivirals with complementary resistance profiles.
"We are very encouraged by the preliminary efficacy and safety data with PSI-938, our purine nucleotide analog for HCV," said Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "These data provide the first confirmatory evidence that a nucleoside/tide analog can exhibit substantial early antiviral activity in monotherapy as has been observed with compounds in other DAA classes. Unlike other classes of DAAs to date, our nucleotide analogs also provide a higher barrier to resistance and clinically-validated antiviral activity across a broad range of HCV genotypes, characteristics not yet demonstrated with other classes of DAA. We continue to believe that nucleoside/tide analogs will become the backbone of HCV therapy. In addition, similar to HIV, the combination of two complementary nucleoside/tide analogs could provide a differentiated therapy for HCV patients in the future."
PSI-938 and PSI-7977 Combination Study
In this quarter, Pharmasset plans to initiate a short-term study to assess the combination of PSI-938 and PSI-7977. The trial will be conducted in the US, as a blinded, randomized, placebo-controlled study in approximately 50 patients chronically infected with HCV genotype 1. The primary objective will be to assess the safety, tolerability, and pharmacokinetics of PSI-938 and PSI-7977 alone and in combination. Preliminary results are expected in the first half of 2011.
Conference Call and Webcast
Members of Pharmasset's management team will host a conference call today, October 28, 2010, at 8:00 a.m. ET to discuss the preliminary results of the multiple ascending dose trial with PSI-938. Investors may listen to the webcast of the conference call live on the "Events & Presentations" section of Pharmasset's website, www.pharmasset.com. Alternatively, investors may listen to the call by dialing 877-771-7028 from locations in the U.S. and 973-200-3092 from outside the U.S. The webcast replay will be available for at least 72 hours following the call.
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 on the development of oral therapeutics for the treatment of hepatitis C virus (HCV). Our research and development efforts focus on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have four clinical-stage product candidates. RG7128, a cytosine nucleoside analog for chronic HCV infection, is in two Phase 2b clinical studies in combination with Pegasys(R) plus Copegus(R) and is also in the INFORM studies, the first series of studies designed to assess the potential of combinations of small molecules without Pegasys(R) and Copegus(R) to treat chronic HCV. These clinical studies are being conducted through a strategic collaboration with Roche. Our other clinical stage HCV candidates include PSI-7977, an unpartnered uracil nucleotide analog presently in a Phase 2b study, and PSI-938, an unpartnered guanosine nucleotide analog in Phase 1. We also have in our pipeline an additional purine nucleotide analog, PSI-661, in advanced preclinical development. Racivir, for the treatment of HIV, has completed a Phase 2 clinical study.
Pegasys® and Copegus® are registered trademarks of Roche.
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