Friday, May 28, 2010

Roche Diagnostics gets FDA premarket approval for HCV antibody assay.

INDIANAPOLIS, May 28 /PRNewswire/ -- Roche Diagnostics announced today that the U.S. Food and Drug Administration (FDA) granted Premarket Approval for its Elecsys Antibody to hepatitis C virus (anti-HCV) assay. The Elecsys Anti-HCV assay is an in-vitro diagnostic test for the qualitative detection of total antibodies to hepatitis C virus in human serum or plasma.

Roche received approvals for the anti-HCV test on three platforms: the stand-alone cobas e 411 analyzer for low-volume testing; and the cobas e 601 and MODULAR ANALYTICS E 170 analyzers, which are modules of consolidated immunoassay/clinical chemistry systems for mid-volume and high-volume testing, respectively.
The anti-HCV assay is an 18-minute test designed for use with Roche's electrochemiluminescence (ECL) technology. Assay results, in conjunction with other laboratory results and clinical information, may be used to aid in the presumptive diagnosis of HCV infection in persons with signs and symptoms of hepatitis and in persons at risk for hepatitis C infection. The test does not determine the state of infection or associated disease.
Roche received FDA 510(k) clearance for another immunoassay in its infectious disease portfolio, Rubella IgM, in April. The Elecsys anti-HCV assay is anticipated to ship in July.

Thursday, May 27, 2010

Intermune initiates major restructuring plan - will it effect future of HCV pipeline?

ITMN initiated a restructuring plan that will reduce 40% of its workforce by the end of June 2010 and is expected to generate approximately $12mn in cost savings annually. The workforce reduction follows the FDA's Complete Response Letter requesting data from an additional clinical trial before considering the regulatory approval of pirfenidone for the treatment of declining lung function in patients with idiopathic pulmonary fibrosis (IPF).


The FDA's complete response letter left ITMN in a difficult position both strategically and financially, with the company waiting for a 1H11 regulatory decision for pirfenidone in Europe while continuing to advance its HCV candidate, ITMN-191/RG7227, through ongoing Phase IIb trials. In order to further minimize costs, analysts believe ITMN could look to renegotiate the terms of its development and commercialization agreement with Roche, potentially moving from a cost/profit sharing arrangement to a straight royalty-based arrangement that would no longer require the one-third contribution of development costs.

InterMune currently has 146 employees.

Wednesday, May 26, 2010

More on ADVANCE results for Telaprevir from Reuters

Hep C drug achieves 75 percent cure rate: study




(Reuters) - A hepatitis C treatment being developed by Vertex Pharmaceuticals Inc led to a 75 percent cure rate in a pivotal trial of previously untreated patients, the company said on Tuesday.



The results from the first late-stage Phase III study of telaprevir came in at the high end of expectations for a cure rate of 70 to 75 percent, with slightly lower discontinuation rates due to side effects than previously seen.



Investors cheered the data, sending Vertex shares, which have slumped recently, up 12 percent in after-hours trading.



Telaprevir is expected to become a multibillion-dollar drug for Vertex if approved by the U.S. Food and Drug Administration.



Seventy-five percent of patients who received 12 weeks of telaprevir in combination with current standard treatment of pegylated interferon and ribavirin, followed by either 12 or 36 weeks of standard treatment achieved a sustained virologic response, or SVR, which is tantamount to a cure.



That compared with a 44 percent SVR rate for patients who received the usual 48-week regimen of the standard drugs.



"I think it is a bellwether day for hepatitis C drug development. It's really impressive to see a 75 percent SVR rate in a Phase 3 pivotal trial," said Sanford Bernstein analyst Geoffrey Porges.



He said the result "sets a very high hurdle for competitors."



Porges previously had said a telaprevir SVR rate below 65 percent would be a disappointment and anything north of 80 percent would send the stock skyrocketing.



A member of Porges' household maintains a long position in Vertex.



Telaprevir is in a race with a similar drug called boceprevir being developed by Merck & Co.



Data from two more Phase III trials of telaprevir, including results in patients who failed with previous treatment, is expected in the third quarter. The first boceprevir late-stage data will be released later this year.



Through mid-stage studies, most analysts have tabbed the Vertex drug as superior.



In a third arm of the Phase III study, 69 percent of patients who received the telaprevir combination for just eight weeks followed by either 16 or 40 weeks of the standard drugs achieved SVR, Vertex said.

The results were "in line with what the Street was looking for, but certainly not above expectations, or below them for that matter," said Brian Skorney, an analyst for Thinkequity.



There has been great hope for this new class of antiviral drugs for the serious liver disease because of the potential for significantly higher cure rates and the possibility of cutting the duration that the standard drugs must be taken.



The tough to tolerate standard drugs -- interferon and ribavirin -- offer cure rates in the 40 percent to 50 percent range, must be taken for 48 weeks, and often cause debilitating flu-like symptoms, causing many patients to discontinue their use.



Several drugmakers are working on next generation drugs with the hope they could be combined with treatments like telaprevir and eliminate the need for interferon altogether.



Analysts and investors should also be pleased with telaprevir discontinuation rates due to adverse events that were a bit lower than those seen in Phase II studies.



"Discontinuations due to rash were lower," Skorney said.



The discontinuation rate was 6.9 percent in the 12-week telaprevir arm, 7.7 percent in the 8-week arm and 3.6 percent with the standard drugs alone.



Viral relapse rates -- patients who had achieved undetectable levels of the virus in the blood only to relapse after completing treatment -- were much lower in the telaprevir arms of the study.



The relapse rate was 8.6 percent among patients who received 12 weeks of telaprevir and 9.5 percent for those who got the Vertex drug for 8 weeks. That compared with a 28 percent viral relapse rate on the standard drugs.



"The results highlight that telaprevir-based combination regimens may increase viral eradication rates and shorten treatment time for many patients," Dr Ira Jacobson from Weill Cornell Medical College and a researcher for the study, said in a statement.



Vertex shares rose to $38 in after hours trading from their Nasdaq close at $33.95.

Tuesday, May 25, 2010

Vertex's Telaprevir exceeds Wall Street expectations with Phase III ADVANCE trial in Tx naive subjects

75% of Treatment-Naïve Patients with Chronic Hepatitis C Achieve SVR (Viral Cure) with Telaprevir-Based Treatment in Phase 3 Trial

-Majority of patients treated with telaprevir received a 24-week regimen-
-6.9% and 7.7% treatment discontinuation rates due to adverse events in 12- and 8-week telaprevir-based treatment arms -- lower than previous telaprevir trials-
-First Phase 3 trial results for a direct acting antiviral therapy in hepatitis C-


CAMBRIDGE, Mass., May 25, 2010 (BUSINESS WIRE) -- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that 75% of people chronically infected with genotype 1 hepatitis C virus (HCV) who had not previously been treated achieved a sustained viral response (SVR or viral cure) after receiving a 12-week telaprevir-based combination regimen, followed by treatment with pegylated-interferon and ribavirin alone, in the Phase 3 ADVANCE trial. 69% of people achieved SVR after receiving an 8-week telaprevir-based combination regimen, followed by treatment with pegylated-interferon and ribavirin alone. 44% of people in the control arm achieved SVR after 48 weeks of treatment with the currently approved regimen of pegylated-interferon and ribavirin.
The safety and tolerability profile of telaprevir in the ADVANCE trial was consistent with the profile reported in Phase 2 studies, with an improvement in treatment discontinuation rates due to adverse events. Adverse events leading to discontinuation of all study drugs occurred in 6.9%, 7.7% and 3.6% of patients in the 12-week telaprevir-based arm, the 8-week telaprevir-based arm and the control arm, respectively.
"These first Phase 3 results are important for people with hepatitis C, as they represent a potential new era of therapy where doctors may be able to use direct acting antiviral medicines to improve treatment and help patients potentially avoid life-threatening liver-related consequences associated with chronic hepatitis C," said Ira Jacobson, M.D., Chief of the Division of Gastroenterology and Hepatology, Weill Cornell Medical College, and an Investigator for the ADVANCE trial. "The ADVANCE results confirm findings seen in earlier trials of telaprevir and highlight that telaprevir-based combination regimens may increase viral eradication rates and shorten treatment time for many patients."
"These groundbreaking data are the result of our more than decade-long commitment to improving care for people with hepatitis C and should provide new hope for patients with this disease," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. "As fewer than half of people with genotype 1 hepatitis C achieve a viral cure with currently approved therapies, new and more effective medicines are urgently needed.
"These results for telaprevir show that 75 percent of patients in the 12-week telaprevir arm achieved a viral cure, with the majority receiving only 24 weeks of therapy, marking what we believe may be a potentially dramatic improvement in the future treatment of hepatitis C," concluded Dr. Kauffman.
Telaprevir is an investigational, oral inhibitor of HCV protease, an enzyme essential for viral replication, and is being developed by Vertex Pharmaceuticals in collaboration with Tibotec Pharmaceuticals and Mitsubishi Tanabe Pharma. Vertex plans to submit a New Drug Application to the U.S. Food and Drug Administration (FDA) for telaprevir in the second half of 2010 for both treatment-naïve and treatment-failure patients.
About the ADVANCE Trial
ADVANCE was a Phase 3, randomized, double-blind, placebo-controlled trial that enrolled approximately 1,095 people infected with genotype 1 chronic HCV, the most common form of the virus in the U.S. and Europe, who had not previously been treated for their HCV infection. The trial enrolled patients at 114 international clinical trial sites worldwide. Approximately 60% of the patients in ADVANCE were enrolled at trial sites in North America. Additionally, approximately 20% of the patients in ADVANCE were African American, Black, Hispanic or Latino, and approximately 20% had advanced fibrosis or cirrhosis.
The primary endpoint of the ADVANCE trial was SVR defined as the proportion of patients who had undetectable HCV RNA both at the end of treatment and 24 weeks after the end of treatment. The secondary endpoint was to evaluate the safety of telaprevir when dosed in combination with pegylated-interferon and ribavirin.
As part of a response-guided design, patients in the telaprevir-based treatment arms who had undetectable HCV RNA (<25IU/mL and undetectable by Roche COBAS Taqman HCV test) at Week 4 and Week 12 of treatment were eligible to receive 24 total weeks of therapy. Patients who did not meet the response-guided criterion but were undetectable at Week 24 received 48 total weeks of therapy. Patients received 750 mg of telaprevir (or placebo) orally (tablets) every eight hours (q8h), a 180 ug injection of peginterferon alfa-2a (Pegasys) once-weekly, and a 1,000 mg or 1,200 mg weight-based daily oral dose of ribavirin (Copegus).
SVR Results (Intent to Treat Analysis)
Telaprevir-Based
Treatment Arm
SVR Rate Treatment Regimen
12-week telaprevir-based arm: 75%
(p<0.0001)
12 weeks of telaprevir, pegylated-interferon and ribavirin followed by 12 or 36 weeks of only pegylated interferon and ribavirin, based on response to treatment at Week 4 and Week 12
8-week telaprevir-based arm: 69%
(p<0.0001)
8 weeks of telaprevir, pegylated-interferon and ribavirin followed by 16 or 40 weeks of only pegylated interferon and ribavirin, based on response to treatment at Week 4 and Week 12
Control arm: 44% 48 weeks of pegylated-interferon and ribavirin
The SVR rates observed in the two telaprevir-based treatment arms were statistically significant when compared to the control arm (p<0.0001).
For patients in the 12-week telaprevir-based arm, the 8-week telaprevir-based arm and the control arm, 68%, 66% and 9%, respectively, had undetectable HCV RNA 4 weeks after the initiation of treatment, defined as a rapid viral response (RVR) by the American Association for the Study of Liver Diseases Practice Guidelines.1
Viral Relapse Rates
For patients in the 12-week telaprevir-based treatment arm, the 8-week telaprevir-based treatment arm and the control arm, 8.6%, 9.5% and 28%, respectively, experienced viral relapse (defined as the proportion of patients who achieved undetectable HCV RNA at the completion of all treatment but relapsed during post-treatment follow up).
Safety & Tolerability Results from ADVANCE
The safety and tolerability profile of telaprevir in the ADVANCE trial was consistent with the profile reported in Phase 2 trials of telaprevir, with an improvement in treatment discontinuation rates due to adverse events, including rash and anemia. The most common adverse events reported in the telaprevir arms were fatigue, rash, pruritus, nausea, headache and anemia, of which anemia, rash, pruritus and nausea occurred more frequently in the telaprevir-based treatment arms than in the control arm. The majority of these adverse events were mild to moderate.
Adverse events leading to discontinuation of all study drugs occurred in 6.9%, 7.7% and 3.6% of patients in the 12-week telaprevir-based arm, the 8-week telaprevir-based arm and the control arm, respectively. Discontinuation of all treatment due to rash was 1.4%, 0.5% and 0.0% in the 12-week telaprevir-based arm, the 8-week telaprevir-based arm and the control arm, respectively, while discontinuation due to anemia was 0.8%, 3.3% and 0.6% in the 12-week telaprevir-based arm, the 8-week telaprevir-based arm and the control arm, respectively.
Additional data from the ADVANCE trial will be submitted for presentation at a medical meeting in the second half of 2010.
About the Telaprevir Development Program
To date, more than 2,000 patients with hepatitis C have received telaprevir-based regimens as part of Phase 2 clinical trials and the Phase 3 ADVANCE trial. Together, these trials enrolled both treatment-naïve and treatment-failure HCV patients, including difficult to treat patients such as null responders. The telaprevir clinical development program is the largest conducted to date for any investigational direct-acting antiviral therapy for hepatitis C.
ADVANCE is the first of three clinical trials conducted as part of a global Phase 3 registration program for telaprevir in treatment-naïve and treatment-failure patients with chronic HCV infection. Data from the remaining two clinical trials in the registration program, known as the ILLUMINATE and REALIZE trials, are expected in the third quarter of 2010. ILLUMINATE is evaluating telaprevir-based regimens in approximately 500 treatment-naïve HCV patients. REALIZE is evaluating telaprevir-based regimens in approximately 650 treatment-failure HCV patients.
Telaprevir is being developed by Vertex Pharmaceuticals in collaboration with Tibotec Pharmaceuticals and Mitsubishi Tanabe Pharma. Vertex retains commercial rights to telaprevir in North America. Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.
About Hepatitis C
Hepatitis C is a liver disease caused by the hepatitis C virus (HCV), which is found in the blood of people with the disease.2 While chronic HCV infection affects up to 3.9 million individuals in the United States, 75% of those infected are unaware of their infection.3 Approximately 60 percent of genotype 1 patients who undergo an initial 48-week regimen with pegylated-interferon and ribavirin, the currently approved treatment regimen, do not achieve sustained viral response (SVR),4,5,6 or a virologic cure. 1
HCV is spread through direct contact with the blood of infected people.2 Though many people with HCV infection may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.2 Chronic HCV can lead to serious liver problems, including liver damage, cirrhosis, liver failure, or liver cancer.2 If treatment is not successful and patients do not achieve an SVR, they remain at risk for progressive liver disease.7,8,9,10,11 In the United States, HCV infection is the leading cause of liver transplantations and is reported to contribute to 4,600 to 12,000 deaths annually.8 The majority of patients infected with HCV were born between 1946 and 1964, accounting for two of every three chronic HCV cases.11 Over the next 20 years, total annual medical costs for patients with HCV infection are expected to more than double, from $30 billion today to approximately $85 billion.11
Additional resources for media, including an HCV backgrounder and glossary of common terms, are available at: http://investors.vrtx.com/press.cfm
References:
1 Ghany, m.G., Strader, d.B., Thomas, d.L., Seeff, Leondard B. diagnosis, management and Treatment of Hepatitis C; An Update. 2009. Hepatology. 2009;49 (4):1-40.
2 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 May 25, 2010.
3 Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. 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. Accessed May 25, 2010.
4 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.
5 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.
6 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.
7 Morgan T.R, 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 Davis, G.L., Alter, M. J. , El-Serag, H. Clinical-Liver, Pancreas, and Biliary Tract. Journal of Gastroenterology. 2010;138: 513-521.
9 Volk, Michael I., Tocco, Rachel, Saini, Sameer, Lok, Anna S.F. Public Health Impact of Antiviral Therapy for Hepatitis C in the United States. Hepatology.2009;50(6):1750-1755.
10 Veldt, B.J., 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.
11 Pyenson, B., Fitch, K., Iwasaki, K. Consequences of Hepatitis C Virus (HCV): Costs of a Baby Boomer Epidemic of Liver Disease. Milliman, Inc. This report was commissioned by Vertex Pharmaceuticals, Inc. May, 2009.

IL28B allele in SOC arm of Anadys Pharmaceuticals ANA598 clinical study leading to a higher cEVR than previously seen in SOC arm?

Anadys Pharmaceuticals announced that it has completed 12-week results from an ongoing Phase II study, which demonstrated that 75% of HCV patients treated with 400 mg ANA598 twice daily in combination with pegylated interferon and ribavirin (current standard of care, or SOC) achieved undetectable levels of virus (1 log from any prior measurement) between weeks 10 and 12. No other patient who received either dose of ANA598 experienced viral breakthrough.


The company can offer additional perspective on the response of the patients who received placebo plus standard of care (control arm) in the study based on a preliminary assessment of IL28B genotyping from approximately 60% of the patients in the Phase II study. Recent scientific studies have shown that individuals with the IL28B CC genotype, present in approximately 37% of Caucasian HCV patients and a lower percentage of patients in other ethnic groups, are substantially more responsive to SOC than patients with other IL28B genotypes. In the SOC control arm of the ANA598 study, 56% of the patients who have been genotyped to date are of the CC genotype while in the ANA598-treated arms only 21% of the patients who have been genotyped to date are of the CC genotype. The company believes that the high proportion of CC patients in the SOC control arm of the ANA598 Phase II study relative to the overall population likely contributed to a higher cEVR rate than has been seen historically.


Source: http://www.anadyspharma.com/pr_pdfs/ana598%20complete%2012-week%20data%20%20final%205.21.10.pdf 

Monday, May 24, 2010

Tibotec to study Protease Inhibitor TMC435 Photosensitivity in Healthy Volunteers

According to Clinical Trials.gov, Tibotec has plans to randomize 36 healthy volunteers to 75mg and 100mg QD of TMC435, or TMC435 placebo, or ciprofloxacin (500 mg BID) for  a total of 9 days.
Phototesting will be done  3 days before start of study medication starts and 3 days (Days 8, 9 and 10) during treatment.  Investigators will assess skin reactions, general tolerability and safety of TMC435 throughout the trial period (or longer if needed). Blood and urine samples will be taken at screening, on day 1, day 7, day 10 and at 2 follow-up visits. Plasma levels of TMC435 and ciprofloxacin will be determined on Day 1, 5, 6, 7 (16 times), 8 (twice), 9 (twice) and 10. ECG and vital signs will be taken at screening, on day 1, twice on day 7, on day 10 and at 2 follow-up visits. A physical examination will be done at screening, on day 1, day 10 and at both follow-up visits. This is planned to start shortly and is estimated to be completed in November 2010

Friday, May 21, 2010

Erythropoiesis Stimulating Agents (ESAs) not allowed in new DAA trials?

Some field intelligence reveals that Erythropoiesis Stimulating Agents (ESAs) are not being allowed in some of  current clinical HCV trials sponsored by Roche, BI, and Tibotec.  If this is true, and ESAs are not needed with these new compounds in development, the life cycle for Schmerck's Boceprevir may be very, very short. Good thing they now have plenty of ammo in the pipeline.

Anadys Climbs On Hepatitis C Study - FOXBusiness.com

Anadys Climbs On Hepatitis C Study - FOXBusiness.com

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Thursday, May 20, 2010

University of Edinburgh scientists develop new test to determine best treatment for HCV

New customised treatment for hep C
Customised treatments for hepatitis C patients are being developed by scientists at a leading university.

A new test is said to rule out the trial and error of patients being prescribed different courses of drugs to treat the infectious disease.

Scientists at the University of Edinburgh say they can test how effective drugs will be for the patient before they are prescribed.

Only one antiviral treatment for hepatitis C is currently available but new drugs are likely to be approved next year, which will be screened using the new method developed in Edinburgh.

The scientists also said the disease can be monitored to check when it is becoming resistant to drugs and the effectiveness of switching to other treatments can be evaluated.

Researcher Ingrid Imhof, of the university's centre for infectious diseases, said: "This new system will make it easier to select in advance the best treatment option for each individual patient, saving them from ineffective treatments with potentially serious side-effects."

All six strains of hepatitis C were use to infect liver cells. The cells were then tested using a range of drugs.
The team, led by Professor Peter Simmonds, analysed each strain of the disease to check the effectiveness of the drugs and any resistance to them. The study findings were published in the Journal of Virology. An estimated 250,000 people in the UK and around 170 million people around the world have hepatitis C.

The disease, which often has no symptoms, can cause swelling and scarring of the liver. Carriers can have the disease for years without knowing.

Symptoms, when apparent, are fatigue, alcohol intolerance and weight loss. Long-term carriers are more at risk of developing liver disease and liver cancer.

Vertex Awaits Final Proof that Hepatitis C Drug Works

Vertex Awaits Final Proof that Hepatitis C Drug Works

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