Data from the PROVE3 trial published today in the New England Journal of Medicine show that telaprevir-based regimens are significantly more effective than the current standard of care in helping patients with chronic genotype 1 hepatitis C virus (HCV) who failed previous therapy achieve a sustained virologic response (SVR).1 Study participants, who had failed prior treatment with pegylated interferon combined with ribavirin, were randomly assigned to one of four treatment regimens, three of which contained telaprevir,1 an investigational DAA (Direct Acting Antiviral) being co-developed by Tibotec and Vertex Pharmaceuticals.

Chronic infection with HCV can cause severe liver problems, including liver cancer and cirrhosis, and is the most common cause of liver transplant in Europe.2 The goal of HCV treatment is to achieve SVR, which means the virus remains undetectable in patients' blood six months after they have finished treatment. Patients who achieve SVR are considered cured.3 The current standard of care for HCV, pegylated interferon combined with ribavirin, may cause side effects2 and cures only about half of patients with genotype 1 starting therapy for the first time. For those that fail therapy, re-treatment with standard of care is effective in a very limited proportion of patients.2

"People with HCV who fail to achieve SVR after initial treatment typically don't succeed when they are re-treated. This study shows that telaprevir may provide a much-needed new therapeutic option for patients undergoing a second round of treatment," said Michael P. Manns, M.D., Professor and Chairman, Department of Gastroenterology, Hepatology and Endocrinology Medical School of Hannover, Germany and investigator in the PROVE 3 study. "The study also gave us important insights into the types of patients who are likely to respond to re-treatment."

In the study, patients were randomized to receive one of four courses of treatment:1

- T12PR24 (N=115): Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks followed by placebo and peginterferon alfa-2a and ribavirin for 12 weeks
- T24PR48 (N=113): Telaprevir plus peginterferon alfa-2a and ribavirin for 24 weeks followed by peginterferon alfa-2a and ribavirin for 24 weeks
- T24P24 (N=111): Telaprevir and peginterferon alfa-2a for 24 weeks
- PR48 (control) (N=114): Placebo plus peginterferon alfa-2a plus ribavirin for 24 weeks followed by peginterferon alfa-2a and ribavirin for 24 weeks

The rate of achieving SVR, the study's primary efficacy endpoint, was significantly higher in each of the telaprevir groups compared with the control group. SVR rates were as follows: 51 percent (P Among prior relapsers, SVR rates were 69 percent in the T12PR24 group, 76 percent in the T24PR48 group, 42 percent in the T24P24 group, and 20 percent in the control group. Among prior nonresponders, SVR rates were 39 percent in the T12PR24 group, 38 percent in the T24PR48 group, 11 percent in the T24P24 group, and 9 percent in the control group.1 Viral breakthrough rates through Week 24 were 13 percent in the T12PR24 group, 12 percent in the T24PR48 group, 32 percent in the T24P24 group, and 3 percent in the PR48 group. In all telaprevir treatment groups, the majority of patients with viral breakthrough were prior nonresponders.1

"We are pleased to publish such promising data for a patient population that currently has so few treatment options," said Maria Beumont-Mauviel, Medical Director, Clinical Development, Tibotec. "We're continuing to evaluate the safety, efficacy, and optimal dosing regimen for telaprevir in a pivotal clinical trial program."

Data from the PROVE1 and PROVE2 studies, which examined telaprevir in treatment-naïve genotype 1 HCV patients, were published in the 30 April 2009 issue of the New England Journal of Medicine.

About PROVE3

PROVE3 was a randomized, stratified, partially placebo-controlled, partially double-blinded phase 2 study of 453 patients with HCV who had failed previous treatment with the current standard of care.1 In PROVE3, patients were categorized by prior treatment responses as patients with nonresponse, relapse and breakthrough.1

Nonresponders were defined as patients who never achieved undetectable HCV RNA during a prior treatment. Relapsers were patients who had undetectable HCV RNA at the completion of prior treatment but then had detectable HCV RNA during follow-up and did not achieve SVR. Viral breakthrough patients achieved undetectable HCV RNA during prior treatment but then became detectable again before the end of prior treatment.1

Telaprevir was given at a single oral dose of 1250 mg for the first dose followed by a dose of 750 mg every 8 hours for the predefined treatment period. Peginterferon alfa-2a was administered at 180 µg each week by subcutaneous injection. Ribavirin was administered twice daily at 1000 mg per day for patients weighing