Vertex Reports Encouraging Data from PROVE3 Trial of HCV Protease Inhibitor Tela

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Vertex Reports Encouraging Data from PROVE3 Trial of HCV Protease Inhibitor Telaprevir (VX-950)

Given the limitations of standard interferon-based therapy for chronic hepatitis C virus (HCV), researchers are studying several directly-targeted agents that interfere with various stages of the viral life cycle, an approach known as specifically targeted antiviral therapy for HCV, or "STAT-C."

Vertex Pharmaceuticals last week reported promising interim data from the PROVE3 trial of the investigational oral HCV protease inhibitor telaprevir (VX-950) in combination with pegylated interferon, with or without ribavirin, in prior non-responders with genotype 3 HCV.

Below is an edited excerpt from the company's recent press release announcing the latest findings. Data from the PROVE1 and PROVE2 studies were presented in April at the 43rd annual meeting of the European Association for the Study of the Liver (EASL).

Vertex Reports 52% SVR 12 Rate for a 24-week Telaprevir-based Regimen in Genotype 1 Hepatitis C Patients Who Failed Prior Treatment

• 73% of prior relapsers achieved SVR12 with 24-week telaprevir-based treatment.• 41% of prior non-responders achieved SVR12 with 24-week telaprevir-based regimen.

Cambridge, Mass., Jun 09, 2008 -- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced positive results from a planned interim analysis of PROVE 3, an ongoing Phase 2b study evaluating telaprevir-based treatment in patients with genotype 1 chronic hepatitis C virus (HCV) infection who did not achieve sustained virologic response (SVR) with at least one prior pegylated interferon (peg-IFN) and ribavirin (RBV) regimen. Vertex is developing telaprevir in collaboration with Tibotec. In the interim analysis, 52% (60 of 115; intent-to-treat analysis) of patients randomized to receive treatment with a 24-week telaprevir-based regimen (12 weeks of telaprevir in combination with peg-IFN and RBV, followed by 12 weeks of peg-IFN and RBV alone) maintained undetectable HCV RNA 12 weeks post-treatment (SVR12). In the interim analysis, adverse events were similar to those commonly observed with peg-IFN and RBV including fatigue, nausea, rash, headache, gastrointestinal disorders, and anemia, and were consistent with those previously reported in patients being treated with telaprevir-based therapy in the PROVE 1 and 2 studies in treatment-naive subjects. Based on these data, Vertex and Tibotec plan to initiate a Phase 3 clinical trial in patients who have failed prior treatment with peg-IFN and RBV. Telaprevir is the most advanced HCV protease inhibitor in clinical development targeting treatment of chronic hepatitis C, and is in Phase 3 clinical development in treatment-naive patients. Hepatitis C is a disease that afflicts more than 3 million people in the United States alone, and 170 million worldwide. Interim Analysis Results PROVE 3 is a randomized, double-blind, placebo-controlled Phase 2b study that enrolled patients who failed prior treatment with peg-IFN and RBV. Patients enrolled in PROVE 3 included prior non-responders (including null responders), prior relapsers, and prior breakthroughs to peg-IFN and RBV treatment. The interim analysis included 453 patients that were enrolled and received at least one dose of study drug. In the interim analysis, 52% (60 of 115) of patients randomized to receive a 24-week telaprevir-based regimen (12 weeks of telaprevir in combination with peg-IFN and RBV, followed by 12 weeks of peg-IFN and RBV alone) achieved undetectable HCV RNA (less than 10 IU/mL; Roche TaqMan) 12 weeks post-treatment (SVR12). Of the 115 patients, 66 were categorized as non-responders to prior treatment (defined as patients who never achieved undetectable HCV RNA during prior treatment, including null responders), 40 were prior relapsers (defined as patients who had undetectable HCV RNA at the completion of prior treatment, but relapsed during follow-up), and 9 were prior breakthroughs (defined as patients who had viral rebound during prior treatment). Among patients receiving the 24-week telaprevir-based regimen, 41% (27 of 66) of the prior non-responders, 73% (29 of 40) of prior relapsers, and 44% (4 of 9) of prior breakthroughs achieved SVR12. "Patients who have not achieved a sustained virologic response with one or more courses of prior interferon-based therapy represent a significant unmet medical need. These patients have few or no available treatment options and they are at increased risk for progressive liver disease," said McHutchison, MD, Principal Investigator for the PROVE 3 Study and Associate Director of Duke Clinical Research Institute. A summary of available on-treatment and post-treatment antiviral data from the 24-week telaprevir-based regimen is presented below:

Undetectable HCV-RNA by Response to Prior Peg-IFN/RBV Treatment

Week 12

Week 24(end of treatment)

SVR 12(week 36; 12 weeks post-treatment)

Non-responders (n=66)

71%

65%

41%

Relapsers (n=40)

88%

83%

73%

Breakthroughs (n=9)

44%

44%

44%

Total (n=115)

75%

70%

52%

In the control arm (n=114), which is evaluating 48 weeks of peg-IFN and RBV only, available data indicate that 8% of patients had undetectable HCV RNA at week 12, and 30% had undetectable HCV RNA at week 36 on-treatment (intent-to-treat analysis). In prior studies of peg-IFN and RBV in treatment-failure patients, the proportion of patients who had undetectable HCV RNA at week 36 of treatment has been significantly higher than the proportion who ultimately achieved SVR. End-of-treatment and post-treatment data (including SVR rates) are not yet available for this study arm in PROVE 3. In addition to the 24-week telaprevir-based regimen that includes ribavirin and the 48 week control arm described above, two other treatment regimens are being evaluated in PROVE 3: a 24-week telaprevir treatment arm without ribavirin, and a 48-week treatment arm that includes 24 weeks of telaprevir dosing in combination with peg-IFN and RBV. The interim analysis supports the inclusion of ribavirin in future studies of telaprevir-based regimens in treatment-failure patients, similar to what has been observed in treatment-naive subjects. In addition, available on-treatment results suggest that additional dosing of telaprevir beyond 12 weeks does not confer additional benefit to patients. Patient dosing has now been completed in PROVE 3 and all patients are now being followed post-treatment. Vertex anticipates that PROVE 3 data will be the subject of a presentation at a medical conference later in 2008. "These are the first data to show the potential of a STAT-C agent to have this degree of antiviral response in patients -- including both non-responders and relapsers -- who did not achieve SVR with prior treatment. The interim data suggest that a telaprevir-based regimen could be an important future treatment option for genotype 1 hepatitis C patients who have failed a prior course of treatment," said Alam, MD, Executive Vice President, Medicines Development, and Chief Medical Officer of Vertex. "We are now planning to begin a Phase 3 clinical trial with telaprevir in patients who failed prior peg-IFN and ribavirin treatment." In the interim analysis, adverse events were similar to those commonly observed with peg-IFN and RBV including fatigue, nausea, rash, headache, gastrointestinal disorders, and anemia, and were also consistent with those previously reported in patients being treated with telaprevir-based therapy in the PROVE 1 and 2 studies in treatment-naive subjects. Thirteen patients (11%) receiving the 24-week telaprevir based treatment regimen (12 weeks of telaprevir in combination with peg-IFN and RBV, followed by 12 weeks of peg-IFN and RBV alone) discontinued treatment due to adverse events. The most common reason for discontinuation among patients receiving this 24-week telaprevir-based treatment regimen was rash (7% of patients). In the control arm, 5 patients (4%) discontinued treatment prior to week 36 due to adverse events. Phase 3 Study in Patients Who Failed Prior Treatment Vertex and Tibotec plan to initiate a Phase 3 clinical trial in genotype 1 HCV patients who have failed prior treatment with peg-IFN and RBV in the third quarter, which will be led by Tibotec. The randomized, double-blind and placebo-controlled study will focus on regimens of 48 weeks total treatment duration, in which telaprevir is administered for 12 weeks, with a goal of maximizing SVR rates. The study is planned to be conducted at more than 50 centers in the U.S., European Union (E.U.), and certain other countries. Updates on the status of Vertex and Tibotec's clinical trials of telaprevir are available at www.clinicaltrials.gov. About PROVE 3 PROVE 3 is an ongoing, four-arm, Phase 2b clinical trial of 453 genotype 1 HCV patients who did not achieve an SVR with a prior course of peg-IFN and RBV treatment. The study includes patients with compensated cirrhosis. The study is assessing patients who receive telaprevir-based treatment regimens of 24 and 48-week total duration, compared to a 48-week control arm of peg-IFN and RBV. PROVE 3 is being conducted at 50 clinical centers in the U.S. and the E.U. About Telaprevir (VX-950) Telaprevir (VX-950) is an investigational oral inhibitor of HCV protease, an enzyme essential for viral replication, and is the most advanced investigational agent in development that specifically targets HCV. Telaprevir is the first hepatitis C protease inhibitor in Phase 3 clinical trials. The Phase 3 ADVANCE trial is expected to enroll 1,050 treatment-naive genotype 1 HCV patients and will evaluate two 24-week telaprevir-based regimens in comparison to a 48-week control arm. Vertex is also conducting a global Phase 2b clinical development program of telaprevir, including PROVE 1 and PROVE 2 in treatment-naive genotype 1 HCV patients, and PROVE 3 in genotype 1 HCV patients who have not achieved SVR with a prior course of pegylated interferon-based therapy. Vertex retains commercial rights to telaprevir in North America. Vertex and Tibotec are collaborating to develop and commercialize telaprevir in Europe, South America, Australia, the Middle East, and other countries. Vertex is collaborating with Mitsubishi Pharma to develop and 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, inflammation, autoimmune diseases, cancer, pain and cystic fibrosis. Vertex co-discovered the HIV protease inhibitor, Lexiva [fosamprenavir], with GlaxoKline. For further information on Vertex Pharmaceuticals Incorporated, see www.vpharm.com.

6/17/08SourceVertex Pharmaceuticals. Vertex Reports 52% SVR 12 Rate for a 24-week Telaprevir-based Regimen in Genotype 1 Hepatitis C Patients Who Failed Prior Treatment. Press release. June 9, 2008.