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59 Percent of Patients Overall Achieved SVR with Telaprevir-Based Regimens in Study 107 After Not Achieving SVR with at Least One Prior Course of Treatment for Hepatitis C Virus Infection

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

-56% of prior treatment null responder patients achieved SVR with a 48-week telaprevir-based regimen-

-97% of prior treatment relapsers and 55% of prior treatment partial responders achieved SVR with 24-week or 48-week telaprevir-based regimens-

VIENNA--(BUSINESS WIRE)--Apr 15, 2010 - In conjunction with an oral presentation at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL) in Vienna, Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that 59 percent of patients overall who received a telaprevir-based combination regimen in Study 107 achieved a sustained viral response (SVR) after failing to achieve SVR with a least one prior course of treatment for hepatitis C virus (HCV) infection. Specifically, 56% of prior treatment null responders (n=27) achieved SVR after treatment with a 48-week telaprevir-based combination regimen, and 97% of prior treatment relapsers (n=29) and 55% of prior treatment partial responders (n=29) achieved SVR after treatment with a 24-week or 48-week telaprevir-based combination regimen. Ten patients (9%, n=117) discontinued all therapy due to adverse events, with rash being the most common reason for discontinuation.

Study 107 was an open-label Phase 2 rollover study of patients who did not achieve SVR after receiving pegylated interferon (Peg-IFN) and ribavirin (RBV) in the control arms of the Phase 2 PROVE trials of telaprevir. Telaprevir is an investigational oral HCV protease inhibitor being developed by Vertex in collaboration with Tibotec and Mitsubishi Tanabe Pharma. A Phase 3 registration program for telaprevir is nearing completion, in both treatment-naïve and treatment-failure HCV patients. The Phase 3 REALIZE trial is evaluating a 48-week telaprevir-based treatment regimen in treatment-failure patients, including null responder patients. In the second half of 2010, Vertex plans to submit a New Drug Application to the U.S. Food and Drug Administration (FDA) for telaprevir for both treatment-naïve and treatment-failure patients.

“The majority of genotype 1 patients who undergo their first regimen of pegylated-interferon and ribavirin fail to achieve SVR and are left with few options for subsequent re-treatment of their disease," said Thomas Berg, M.D., Medical Development, Hepatology Section, University Clinic, Leipzig, Germany. "Treatment with telaprevir-based regimens in Study 107 resulted in an overall SVR rate of 59 percent across all patients enrolled in the study, with 56 percent of the most difficult-to-treat null responder patients achieving SVR with a 48-week telaprevir-based regimen."

"Study 107 provided important insight into the potential future use of telaprevir-based regimens in the treatment of patients who failed to respond to currently approved therapies,” said Robert Kauffman, M.D., Ph.D., Vertex's Senior Vice President, Clinical Development and Chief Medical Officer. “Based on information generated in Study 107, as well as data from the PROVE 3 clinical trial, we believe that a 48-week treatment regimen may increase the likelihood that certain treatment-failure patients are able to achieve SVR. In our Phase 3 REALIZE trial in treatment-failure patients, we are evaluating a 48-week treatment regimen and are currently awaiting final SVR results, which we expect in the third quarter."

Study 107 Design and Results

Study 107 was an open-label, Phase 2 rollover study of telaprevir in combination with Peg-IFN and RBV in patients who had previously received treatment with Peg-IFN and RBV in the control arms of either of the PROVE 1, PROVE 2 or PROVE 3 trials, and did not achieve SVR. Patients in Study 107 were well-characterized as null responders, partial responders, relapsers or breakthroughs, based on their antiviral response documented as a result of their participation in the control arms of the PROVE clinical trials.

When Study 107 began, all patients were to receive 12 weeks of telaprevir in combination with Peg-IFN and RBV followed by an additional 12 weeks of Peg-IFN and RBV, for a total of 24 weeks of therapy. Stopping rules required any patient who did not achieve HCV RNA of 25 IU/mL or less by week 4 to stop all treatment. In 2008, Study 107 was amended and underwent several changes, most notably to the duration of treatment. The changes to treatment duration in Study 107 were aimed at providing patients with a higher likelihood of achieving SVR. Following the amendments, only patients who did not achieve HCV RNA of 100 IU/mL or less at week 4 were required to stop therapy. In addition, prior treatment null responder patients were to receive a 48-week telaprevir-based treatment regimen. Patients with prior treatment relapse, prior treatment viral breakthrough and prior treatment partial response were eligible to receive a response-guided 24-week telaprevir-based treatment regimen if they achieved undetectable HCV RNA at week 4 and 12, otherwise these patients would receive a 48-week regimen.

A total of 117 patients enrolled in Study 107, including 51 patients with prior treatment null response, 29 patients with prior treatment partial response, 8 patients with prior treatment viral breakthrough, and 29 patients with prior treatment relapse.

An overall SVR rate of 59 percent and an overall relapse rate of 16 percent were observed in Study 107. Sustained viral response rates for each arm of Study 107 are as follows:

SVR in Study 107   Treatment Assignment 1: 12 weeks of telaprevir, Peg-IFN & RBV, followed by 12 weeks of only Peg-IFN & RBV

 

  Treatment Assignment 2:

12 weeks of telaprevir, Peg-IFN & RBV, followed by 36 weeks of only Peg-IFN & RBV

 

  Unassigned:
(2 patients discontinued all therapy prior to week 12 and were thus designated as unassigned)

 

  Total:
Overall SVR Rates

 

  60% (49 of 81)

 

  53% (18 of 34)

 

  100% (2 of 2)

 

  59% (69 of 117)

 

  • Prior Null Response1
  17 % (4 of 24)

 

  56% (15 of 27)

 

  -   37% (19 of 51)

 

  • Prior Partial Response2
  60% (15 of 25)

 

  0% (0 of 3)

 

  100% (1 of 1)

 

  55% (16 of 29)

 

  • Prior Viral Breakthrough3
  86% (6 of 7)

 

  0% (0 of 1)

 

  -   75% (6 of 8)

 

  • Prior Relapse4
  96% (24 of 25)

 

  100% (3 of 3)

 

  100% (1 of 1)

 

  97% (28 of 29)

 

1 Defined as patients who achieved a viral load decline of less than 1 log10 at week 4 or 2 log10 or less at week 12 during prior therapy
2 Defined as patients who had a greater than 2 log10 viral decline at week 12 but had detectable HCV RNA at week 24
3 Defined as patients who had undetectable HCV RNA but relapsed before the end of treatment
4 Defined as patients who had undetectable HCV RNA at the end of treatment with Peg-IFN and RBV but subsequently relapsed

Study 107 Safety and Tolerability

Adverse events reported in Study 107 were similar to those reported in prior Phase 2 trials of telaprevir. The most common adverse events reported were rash (all types), fatigue, pruritus, and headache. Discontinuation of all therapy due to adverse events occurred in 10 patients (9%; n=117), with rash being the most common reason for discontinuation.

About Telaprevir

Telaprevir is an investigational, oral inhibitor of HCV protease, an enzyme essential for viral replication, and is being evaluated as part of a global Phase 3 registration program in more than 2,200 treatment-naïve and treatment-failure patients. Vertex is collaborating with Tibotec and Mitsubishi Tanabe Pharma to develop telaprevir. Vertex retains commercial rights to telaprevir in North America. Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and 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.6 Chronic HCV infection affects up to 3.9 million individuals in the United States1 and is spread through direct contact with the blood of infected people.6 Though many people with HCV infection may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.6 Chronic HCV can lead to serious liver problems, including liver damage, cirrhosis, liver failure, or liver cancer.6 The majority of patients infected with HCV were born between 1946 and 1964, accounting for two of every three chronic HCV cases.7 The majority of patients infected with HCV are unaware of their infection.1 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.7

Current therapies for HCV typically result in a sustained viral response in about half of patients with genotype 1 HCV, the most common strain of the virus.2,3,4 If treatment is not successful and patients do not achieve an SVR, they remain at risk for progressive liver disease.8,9,10,11 The risk of liver failure, liver cancer or death following unsuccessful HCV treatment was assessed at 23% after 4 years, and 43% after 8 years.9

About Vertex

Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, epilepsy, cancer, and pain.

Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.

Lexiva is a registered trademark of the GlaxoSmithKline group of companies.

1 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 March 29, 2010.

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 McHutchison, JG, Manns, MP, Muir, AJ. Retreatment with Telaprevir, Peginterferon, and Ribavirin for Chronic HCV Infection. N Engl J Med 2010; 362(14): 30-41.

6 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 April 2, 2010.

7 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.

8 Davis, G.L., Alter, M. J. , El-Serag, H. Clinical-Liver, Pancreas, and Biliary Tract. Journal of Gastroenterology. 2010;138: 513-521.

9 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.

10 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).

11 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.

Special Note Regarding Forward-looking Statements

This press release contains forward-looking statements, including statements regarding (i) the Phase 3 registration program for telaprevir nearing completion and the expectation that the Company will receive final SVR results from the Phase 3 REALIZE trial in the third quarter of 2010, (ii) the Company's plan to submit a New Drug Application to the FDA in the second half of 2010 for both treatment-naïve and treatment failure patients, (iii) Study 107 providing important insight into the potential future use of telaprevir-based regimens in the treatment of patients who failed to respond to currently approved therapies and (iv) the Company's belief that a 48-week treatment regimen may increase the likelihood that certain treatment-failure patients will be able to achieve SVR. 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 outcomes for each of its clinical trials of telaprevir (including the ongoing Phase 3 clinical trials) may not be favorable or may be less favorable than the outcomes obtained from earlier studies including the 107 Study, that there may be varying interpretations of data produced by one or more of the Company's clinical trials, that regulatory authorities will require more extensive data for a telaprevir NDA filing than currently expected, that future competitive or other market factors may adversely affect the commercial potential for the Company's product candidates 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 the Company's website at www.vrtx.com. The Company disclaims any obligation to update the information contained in this press release as new information becomes available.

EASL Webcast

Vertex Pharmaceuticals will host a webcast today, Thursday, April 15, 2010 at 1:45 p.m. ET. This webcast will be broadcast via the Internet at www.vrtx.com. It is suggested that webcast participants go to the web site at least 10 minutes in advance of the call to ensure that they can access the slides. The link to the webcast is available on the “Finances” page under the “Events and Presentations” button. Following the live webcast, an archived version will be available on Vertex's website until 5:00 p.m. ET on April 29, 2010.

(VRTX-GEN)

 

Contact: Vertex Pharmaceuticals Incorporated
Investors:
Michael Partridge, 617-444-6108 (office), 617-767-6108 (at EASL)
or
Lora Pike, 617-444-6755 (office), 857-413-0947 (at EASL)
or
Media:
Zachry Barber: 617-444-6470 (office), 617-767-9533 (at EASL)
or
Amy Pasqua, 617-444-6075 (office), 617-682-6603 (at EASL)

 

 

Posted: April 2010

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