Staff Writer

While Vertex Pharmaceuticals Inc. advances a pivotal Phase III trial of protease inhibitor telaprevir in treatment-naïve hepatitis C patients, partner Tibotec BVBA kicked off enrollment in a pivotal Phase III trial of the drug for treatment-experienced HCV.

Tibotec is a unit of New Brunswick, N.J.-based Johnson & Johnson, and Vertex previously inked a potential $545 million deal licensing certain telaprevir international rights to another J&J company, Janssen Pharmaceutica NV. Cambridge, Mass.-based Vertex retains North American rights. (See BioWorld Today, July 5, 2006.)

Vertex said in August that it had received regulatory clearance for Tibotec to proceed with the second Phase III telaprevir trial, dubbed REALIZE (Re-treatment of Patients with Telaprevir-based Regimen to Optimize Outcomes).

REALIZE is a randomized, double-blind, placebo-controlled study that will enroll about 650 HCV patients who have failed prior standard-of-care treatment with ribavirin and pegylated interferon.

About 300 of those patients will be either null responders, who achieved less than a 2 log reduction in viral levels after prior treatment, or partial responders, who achieved at least a 2 log reduction but never reached undetectable levels. The remaining 350 patients will be relapsers, who achieved undetectable viral levels with prior treatment but relapsed during follow-up.

Patients will be randomized to one of three 48-week treatment arms: a control group receiving standard ribavirin and pegylated interferon for 48 weeks; a group receiving the standard treatment plus 750 mg of telaprevir every eight hours for the first 12 weeks, followed by 36 weeks of standard treatment only; and a group receiving standard treatment for four weeks, followed by 12 weeks of standard therapy plus 750 mg of telaprevir every eight hours, followed by another 32 weeks of standard treatment only.

The primary endpoint of the study is sustained virologic response defined as undetectable HCV RNA viral levels (less than 10 IU/mL) 24 weeks after the completion of the 48-week treatment regimen.

The standard HCV regimen of ribavirin and pegylated interferon often comes under fire for its 40 percent to 50 percent cure rate, and telaprevir is one of many targeted antivirals seeking to offer improved efficacy.

Yet Patricia Farrell, director of public relations for Vertex, said "very few" studies have evaluated the newer drugs in treatment-experienced patients, and "none have shown real significant efficacy in null responders."

In June, Vertex got a nice stock boost off positive interim data from its ongoing Phase IIb trial in treatment-experienced patients, PROVE3, which established the rationale for the REALIZE trial. Analyst Jason Kolbert, of Susquehanna Financial Group, said previously that while Schering-Plough Corp.'s protease inhibitor boceprevir has shown positive Phase II data in treatment-naïve patients, telaprevir is "the only one to have shown efficacy in a treatment-experienced population."

Vertex and Tibotec said they expect to complete REALIZE enrollment in the first quarter of 2009. Farrell declined to provide further timelines, but Kolbert wrote in a research note that he expects data in mid-2010, potentially supporting a 2011 approval.

Meanwhile, Vertex is well under way with its first pivotal Phase III telaprevir trial, ADVANCE (A New Direction in HCV Care: A Study of Treatment-Naive Hepatitis C Patients with Telaprevir).

Started in March, ADVANCE will enroll 1,050 treatment-naïve HCV patients. While REALIZE uses a 48-week treatment regimen, ADVANCE uses a 24-week regimen, which Farrell noted is "half the time" required for standard therapy. Accordingly, patients in the ADVANCE trial will receive either 48 weeks of standard ribavirin and pegylated interferon or potentially 24 weeks of a telaprevir and standard-of-care regimen.

Farrell said Vertex may provide an update on the ADVANCE trial in the next few weeks.

Although REALIZE and ADVANCE are Vertex's primary pivotal trials for telaprevir, the company said in January that the FDA had requested a confirmatory Phase III study comparing 24-week and 48-week treatment regimens in treatment-naïve HCV patients. Farrell said enrollment in this trial is under way. (See BioWorld Today, Jan. 24, 2008.)

While investors may have to wait until 2010 for Phase III data, they can look forward to several telaprevir presentations at the 59th Annual Meeting of the American Association for the Study of Liver Disease (AASLD), Oct. 31 through Nov. 4 in San Francisco.

Of particular interest will be final results of PROVE2, a Phase II European study evaluating a variety of dosing schedules in treatment-naïve patients; interim results from PROVE3, an ongoing Phase IIb trial in treatment-experienced patients; interim results from Study 107, an ongoing rollover study for patients in the control arms of the PROVE trials who did not achieve a sustained virologic response; and interim results from Study C208, an ongoing Phase II trial of twice-daily telaprevir in treatment-naïve patients.

Editor's note: Check out Friday's issue of BioWorld Today for more previews of data to watch for AASLD.

(Companies included in this article are: Tibotec BVBA, Vertex Pharmaceuticals Inc.