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Interim Phase 2 Data Showed Rapid Viral Response to VX-222 in Combination with Telaprevir, Pegylated-Interferon and Ribavirin Among People With Hepatitis C

Update: Incivek (telaprevir) Now FDA Approved - May 23, 2011

First study to evaluate four-drug, 12-week treatment duration for hepatitis C

BERLIN--(BUSINESS WIRE)--Mar 31, 2011 - Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced interim results from an ongoing Phase 2 study (ZENITH) designed to assess the safety and tolerability of 12-week response-guided treatment regimens with its polymerase inhibitor, VX-222, and its protease inhibitor, telaprevir, in combination with pegylated-interferon and ribavirin in people with genotype 1 chronic hepatitis C who were new to treatment. The study enrolled 106 people into one of four treatment groups. Among those who received VX-222 (400 mg) in combination with telaprevir, pegylated-interferon and ribavirin, interim data showed that 90 percent (27/30) of them had undetectable hepatitis C virus at week 12. Half (15/30) of those in the VX-222 (400 mg) treatment group were eligible to stop all treatment at week 12. People in this same treatment group who were not eligible to stop all treatment at 12 weeks were assigned to receive 24 total weeks of treatment: 12 weeks of the four-drug regimen followed by 12 weeks of pegylated-interferon and ribavirin alone. Preliminary safety results showed that the most frequently reported adverse events were mild gastrointestinal symptoms and mild fatigue. At the time of this analysis, there were no discontinuations due to gastrointestinal symptoms. Data from this study are being presented today at The International Liver Congress™ 2011, the 46th annual meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany.

“Telaprevir triple therapy demonstrated significant improvements in viral cure rates and an ability to halve treatment time to 24 weeks for many people in late-stage studies,” said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. “Reducing treatment time in half again to 12 weeks would be another important advance and the early data from this study provide new information about the potential to do this with a four-drug VX-222 regimen.”

Using an intent-to-treat analysis, 57 percent (17/30) of people treated with VX-222 (400 mg) in combination with telaprevir, pegylated-interferon and ribavirin had undetectable hepatitis C virus by week two. Among people who were treated with VX-222 (100 mg) in combination with telaprevir, pegylated-interferon and ribavirin, 38 percent (11/29) had undetectable hepatitis C virus by week two. To determine if patients were eligible to stop all treatment at 12 weeks in ZENITH, they had to have undetectable hepatitis C virus at weeks two and eight. Using the eligibility criteria for a 12-week total treatment duration, half (15/30) of the patients in the high-dose VX-222 combination group and 38 percent (11/29) in the low-dose combination group were eligible to stop all treatment at 12 weeks. Ninety percent (27/30) of patients in the high-dose VX-222 group had undetectable hepatitis C virus by week 12 as did 83 percent (24/29) in the low-dose VX-222 group. No viral breakthrough was observed through week 12 among patients receiving the four-drug combinations.

“The early data from this study are encouraging because they showed patients had a very rapid decline in hepatitis C virus as early as the second week of treatment,” said Adrian Di Bisceglie, M.D., Chief of Hepatology at Saint Louis University School of Medicine. “Hepatitis C virus was undetectable at week 12 of treatment in 90 percent of patients who received the higher dose of VX-222, and half of those in this treatment group were eligible to stop all treatment at that time.”

ZENITH is an ongoing Phase 2 study that enrolled 106 people and began with four treatment arms evaluating two-drug and four-drug combination regimens. The primary endpoint is safety and tolerability and the secondary endpoint is on-treatment antiviral activity and the proportion of people in each treatment arm who achieve a sustained viral response (SVR, defined as undetectable hepatitis C virus 24 weeks after the end of treatment). The study is designed to evaluate various combinations of VX-222, telaprevir, pegylated-interferon and ribavirin for the treatment of genotype 1 chronic hepatitis C. In this study, VX-222, telaprevir and ribavirin are given twice daily. Arms A (n=18) and B (n=29) were designed to evaluate the all-oral, two-drug combination regimens of VX-222 (400 mg or 100 mg) and telaprevir (1,125 mg). Both of these study arms were discontinued due to a pre-defined stopping rule related to viral breakthrough. Arms C (n=29) and D (n=30) are ongoing and designed to evaluate the four-drug combination regimens of VX-222 (400 mg and 100 mg), telaprevir (1,125 mg), pegylated-interferon and ribavirin. An additional treatment arm has been added to the study to evaluate an all-oral, three-drug regimen of VX-222, telaprevir and ribavirin in people with genotype 1b chronic hepatitis C. This study arm is now open for enrollment. A sixth and final arm may be added to the trial per protocol based on data from the study.

 
ZENITH: Interim Intent to Treat (ITT) Analysis of Arms C and D
      VX-222 (100 mg) /TVR-    
      based arm(+)   VX-222 (400 mg) /TVR-based arm(++)
Week 2 HCV RNA undetectable     38%   57%
      (11/29)   (17/30)

 

Week 2 and 8 HCV RNA     38%   50%
undetectable*     (11/29)   (15/30)
Week 4 HCV RNA undetectable     86%   87%
(RVR)     (25/29)   (26/30)

 

Weeks 12 HCV RNA undetectable     83%   90%
(eRVR)     (24/29)   (27/30)
HCV RNA was evaluated using the TaqMan assay version 2.0.

 

*As part of a response-guided regimen, people who have undetectable hepatitis C virus at weeks 2 and 8 are eligible to stop all treatment at week 12.

 

+VX-222 (100 mg, BID), telaprevir (1,125 mg, BID), Pegasys(R) (pegylated-interferon alfa-2a) and Copegus(R) (ribavirin).

 

++VX-222 (400 mg, BID), telaprevir (1,125 mg, BID), Pegasys(R) (pegylated-interferon alfa-2a) and Copegus(R) (ribavirin).

 

 
Preliminary Safety and Tolerability

The 12-week safety and tolerability results are preliminary and include data on all patients enrolled in the study: those enrolled in the two-drug (n=47) and four-drug (n=59) treatment arms. The most frequent adverse events observed in this study were mild gastrointestinal symptoms (including diarrhea, nausea and vomiting) and mild fatigue. No patients discontinued due to gastrointestinal symptoms.

Preliminary safety data indicate that there were six discontinuations due to adverse events among the four treatment arms through week 12. There were two serious adverse events considered by the investigator to be potentially related to study medication: acute renal failure (Arm B), which resolved after study medications were discontinued and anemia (Arm C). There was one additional severe adverse event reported of pneumonia, septic shock and renal failure; this severe adverse event was considered by the investigator to be unrelated to study medication. The three additional discontinuations included rash (n=2) and a motor vehicle accident with facial fractures (n=1).

About Telaprevir and VX-222

Vertex has two oral medicines in development for the treatment of genotype 1 chronic hepatitis C: telaprevir and VX-222. Telaprevir is an investigational, oral inhibitor that acts directly on the HCV protease, an enzyme essential for viral replication. To date, more than 2,500 people with genotype 1 chronic hepatitis C have received telaprevir in Phase 2 and Phase 3 studies. Vertex has been granted Priority Review for its applications for the approval of telaprevir by the U.S. Food and Drug Administration (FDA) and Health Canada. The FDA has scheduled its Antiviral Drugs Advisory Committee to discuss the New Drug Application for telaprevir on April 28, 2011. A target response date of May 23, 2011 is set under the Prescription Drug User Fee Act (PDUFA).

Vertex is developing telaprevir in collaboration with Tibotec BVBA and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America. Through its affiliate, Janssen, 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.

VX-222 is an investigational, oral, non-nucleoside inhibitor of HCV NS5B polymerase. VX-222 is currently being evaluated in combination with telaprevir, pegylated-interferon and ribavirin in a Phase 2 study. Vertex has worldwide commercial rights for VX-222.

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 Approximately 60 percent of people who undergo treatment of an initial 48-week regimen of pegylated-interferon and ribavirin, the currently approved medicines for genotype 1 hepatitis C, do not achieve SVR,2,3,4 or viral cure.5 If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.6,7

More than 170 million people worldwide are chronically infected with hepatitis C.5 In the United States, nearly 4 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.8 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.9 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.10,11 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

PEGASYS® and COPEGUS® are registered trademarks of Hoffmann-La Roche.

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 (i) the potential importance of reducing treatment time to 12 weeks and early data from this study providing new information about the potential to do this with a four-drug VX-222 regimen; (ii) the early data being encouraging because the data showed patients had a very rapid decline in hepatitis C virus as early as the second week of treatment; (iii) the possibility that a sixth treatment arm may be added to the trial; (iv) the date of the scheduled meeting of the FDA's Antiviral Advisory Committee and (v) the FDA's target response date for the telaprevir NDA. 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 Vertex could experience unforeseen delays in obtaining approval to market telaprevir; that the interim on-treatment data presented in this press release may not be predictive of the final outcomes from this clinical trial, outcomes from any future clinical trials of telaprevir/VX-222 may not be favorable; that future scientific, clinical, competitive or other market factors may adversely affect the potential for telaprevir/VX-222-based therapy 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 aims to discover, develop and commercialize 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.

For more information and to view Vertex's press releases, please visit www.vrtx.com.

(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 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.

3 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.

4 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.

5 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.

6 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).

7 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.

8 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.

9 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.

10 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.

11 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.

Contact: Vertex Pharmaceuticals Incorporated
Media:
Dawn Kalmar, 617-444-6992
Amy Pasqua, 617-444-6992
Zachry Barber, 617-444-6992
mediainfo@vrtx.com
or
Investors:
Michael Partridge, 617-444-6108
Lora Pike, 617-444-6755
Matthew Osborne, 617-444-6057

 

Posted: March 2011

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