Vertex-Phase 3 - Telaprevir- Protease Inhibitor

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Vertex Begins Phase 3 Development of Telaprevir, Investigational Hepatitis C Protease Inhibitor

01/23/2008

CAMBRIDGE, Mass. -- Vertex Pharmaceuticals Incorporated announced that it will begin Phase 3 evaluation of telaprevir, Vertex’s lead investigational hepatitis C protease inhibitor. The primary focus will be a global, three-arm pivotal controlled trial that will evaluate two 24-week telaprevir-based regimens in approximately 1050 treatment-naïve genotype 1 hepatitic C virus (HCV) patients.

In this study, rapid viral response (RVR) criteria will be used to determine which telaprevir patients can stop all treatment at 24 weeks. A second study of approximately 400-500 HCV patients is planned to evaluate a 48-week telaprevir-based regimen, to confirm the results from Phase 2 studies and provide additional evidence that supports the 24-week regimen that is being evaluated in the primary Phase 3 trial. The company expects that both studies will run concurrently and that the first trial will begin enrolling patients in March 2008.

"Data presented in late 2007 from two large Phase 2b studies suggest that telaprevir, dosed in combination with pegylated interferon and ribavirin, may be able to meaningfully increase the proportion of treatment-naïve genotype 1 HCV patients who achieve a sustained viral response, and also cut the current treatment duration in half, to 24 weeks," said McHutchison, MD, principal investigator for the primary telaprevir Phase 3 pivotal study and associate director of Duke Clinical Research Institute. "Telaprevir is the most advanced protease inhibitor in development for hepatitis C, and the initiation of Phase 3 clinical development for this investigational drug will begin the process of helping to further assess its potential efficacy and the safety in a larger number of patients."

In accordance with the design and protocol Vertex submitted to the FDA, the primary pivotal trial will focus on evaluation of 24 weeks of telaprevir-based therapy and will enroll approximately 1,050 treatment-naïve, genotype 1 HCV patients, who will be randomized equally across three treatment arms (approximately 350 patients per arm).

The study will be conducted at approximately 100 centers in the U.S., Eureopean Union, and certain other countries. The study arms will include:

* 24 weeks of therapy, with telaprevir dosed at 750 mg every eight hours (q8h) for 12 weeks in combination with standard doses of pegylated interferon alfa-2a (peg-IFN) and ribavirin (RBV) for 12 weeks, then continuing for another 12 weeks with peg-IFN and RBV alone;* 24 weeks of therapy, with telaprevir dosed at 750 mg every eight hours (q8h) for eight weeks in combination with standard doses of peg-IFN and RBV for eight weeks, then continuing for another 16 weeks with peg-IFN and RBV alone; and* A control arm with standard doses of peg-IFN and RBV dosed for 48 weeks.

Patients in both telaprevir arms who achieve rapid viral response (RVR), defined as undetectable (less than 10 IU/mL) viral levels by the end of week 4, and who stay undetectable at week 12, will receive 24 weeks of treatment. Patients in these treatment arms who do not meet the RVR criteria but are undetectable at week 24 will continue on peg-IFN and RBV for a total duration of 48 weeks.

Concurrent 48-Week Second Study to Support Registration Vertex has agreed to conduct a second well-controlled clinical study as part of the registration program for a treatment-naive indication. The objective of this second study would be to develop additional sustained viral response (SVR) and relapse rate data with 48-weeks' treatment duration that confirm results from the Phase 2 studies, thereby providing additional evidence supporting the 24-week regimen in the Phase 3 trial. The design of this second study is being finalized, but at this time, Vertex expects this study to enroll approximately 400-500 patients, including patients in the control arm.

The primary objective of the two studies will be to assess the proportion of patients in each study arm who achieve SVR, defined as undetectable (less than 10 IU/mL, as measured by the Roche TaqMan® assay) HCV RNA 24 weeks after the completion of dosing. Vertex expects to have SVR data from both studies by mid-2010.

Update on Meeting with FDA Vertex and the FDA met in mid-January 2008 to discuss telaprevir’s Phase 3 development program. This meeting included a review of available data from Phase 2b clinical trials of telaprevir, including newly available post-treatment data from the 48-week treatment arms in PROVE 1. In the control arm of PROVE 1, on an ITT basis, 37 percent of patients had undetectable HCV RNA at 12 weeks post-treatment follow-up. In the 48-week ("12+36") telaprevir-based treatment arm in PROVE 1, also on an ITT basis, 66 percent of patients had undetectable HCV RNA at 12 weeks post-treatment follow-up. The relapse rate in the 48-week telaprevir-based arm in PROVE 1 was 6 percent.

Additional HCV Studies Vertex and Tibotec continue to conduct additional clinical studies to evaluate the potential role of telaprevir treatment for important HCV sub-populations as well as different dosing regimens for telaprevir.

The companies are conducting PROVE 3, a Phase 2b clinical trial of telaprevir-based combination therapy in patients with genotype-1 HCV who have not achieved SVR with a previous pegylated interferon-based treatment. Vertex plans to discuss with regulatory authorities in mid-2008 the next steps in the telaprevir development program for treatment-failure HCV patients after the first interim clinical data are available from the PROVE 3 clinical trial.

Tibotec is conducting a Phase 2 clinical study in Europe to evaluate eight-hourly and 12-hourly dosing of telaprevir in combination with pegylated interferon (Pegasys® or PegIntron™) and ribavirin. Interim 12-week on-treatment data are expected to be available in the second half of 2008.

Tibotec is also conducting a Phase 2 viral kinetics study in Europe to evaluate telaprevir in patients infected with genotype 2/3 HCV. Interim on-treatment data are expected to be available in late 2008.In addition, in December, Tibotec initiated a Phase 2 study in Europe to evaluate telaprevir in patients infected with genotype 4 HCV.

Updates on the status of Vertex and Tibotec’s clinical trials of telaprevir are available at www.clinicaltrials.gov.