SUMMARY: More than half of genotype 1 chronic hepatitis C patients who were not cured with a previous course of interferon-based therapy achieved sustained virological response (SVR) when treated with the HCV protease inhibitor telaprevir plus pegylated interferon and ribavirin, according to a summary provided by Vertex Pharmaceuticals of a study presented this week at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010) in Vienna. Response varied according to type of previous treatment failure; while almost all prior relapsers achieved SVR, prior null responders had the lowest odds of successful treatment.

By Liz Highleyman

Below is an edited excerpt from a Vertex press release describing findings from Study 107, an open-label rollover study of control patients from the PROVE trials. (Final data from PROVE 3 were recently published.)

The EASL abstract -- which includes less complete data than the oral presentation -- can be viewed online.

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

	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 -- April 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-naive 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-naive 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, MD, 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, MD, PhD, 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:

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-naive 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 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.

For further information, see www.vrtx.com.

Investigator affiliations: University Clinic, Leipzig, Leipzig, Germany; Duke University Medical Center, Durham, NC; Vertex Pharmaceuticals Incorporated, Cambridge, MA; Cedars-Sinai Medical Center, Los Angeles, CA; Bon Secours Health System, Liver Institute of Virginia, Newport News, VA; University of Vienna, Vienna, Austria; University of Toronto, Toronto, Ontario, Canada; Hôpital Henri Mondor, Créteil, France; Johann Wolfgang Goethe University Medical Center, Frankfurt/Main, Germany; Academisch Medical Center, University of Amsterdam, Amsterdam, Netherland; Royal Free and University College School of Medicine, London, UK.

4/16/10

Source
Vertex Pharmaceuticals. 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. Press release. April 15, 2010.

ReferenceT Berg, JG Mchutchison, N Adda, and others. SVR with telaprevir, peginterferon alfa-2a and ribavirin in HCV patients with well-characterized prior null response, partial response, viral breakthrough or relapse after PR. 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010). Vienna, Austria. April 14-18, 2010. (Abstract).