Breakthrough HCV Therapy?
Experimental HCV Protease Inhibitor VX-950 Demonstrates Potent Anti-HCV Activity
Interim results of a Phase Ib study indicate that the experimental hepatitis C virus protease inhibitor VX-950 has potent anti-HCV activity and is well tolerated, according to an announcement from drug maker Vertex Pharmaceuticals. Within three days of treatment, the median reduction in HCV-RNA was greater than 3 log10 in all three VX-950 dose groups.
As an oral drug that shows potency and no serious adverse side effects, VX-950 has the potential to become a breakthrough therapy for chronic hepatitis C.
The study enrolled 34 patients with chronic genotype 1 HCV infection who were treated for 14 days with placebo or one of three dose regimens of VX-950. HCV genotype1 infection is the most difficult strain of HCV to treat and the most prevalent strain in the United States, Western Europe and Japan.
Every patient receiving VX-950 achieved greater than a 2 log10 reduction in HCV-RNA within the first three days of treatment, according to Vertex.
Complete results from the study will be presented on May 17 at DDW 2005 in Chicago. In accordance with the DDW embargo policy of the meeting, the specific data from the trial beyond what is described in today’s announcement from Vertex will not be disclosed until the DDW presentation.
The Phase Ib clinical trial was a double-blind, randomized placebo-controlled study designed to evaluate the tolerability, pharmacokinetics and effect on viral kinetics of three doses of VX-950 — 450 mg every 8 hours, 1250 mg every 12 hours, or 750 mg every 8 hours — over a period of 14 days, with additional post-treatment follow-up.
A key goal of the study was to assess different dosing levels and frequencies for VX-950 to provide insight into dose selection for future monotherapy and combination therapy studies. Thirty-four patients with chronic genotype 1 hepatitis C virus infection were enrolled in the study; six patients received placebo and 28 patients received VX-950. The study was conducted at three centers in Europe. The trial included treatment-experienced and treatment-naive HCV-infected patients.
Principal results of the Phase Ib clinical trial are as follows:
- VX-950 was well-tolerated across all three dose groups with no serious adverse events reported, and no treatment discontinuations.
- Treatment with VX-950 also resulted in significant reductions in plasma HCV-RNA. Within three days of treatment, the median reduction in HCV-RNA was greater than 3 log10 in all three VX-950 dose groups.
- In the dose group receiving 750 mg of VX-950 every 8 hours, there was a further reduction in viral levels between days 3 and 14 of treatment, with mean and median HCV-RNA reductions of greater than 4 log10 at day 14.
- Trough plasma concentrations of VX-950 were highest in the 750 mg every 8 hour dose group. In the 450 mg q8h and 1250 mg q12h dose groups, maximal effects were seen between days 3 and 7 of treatment.
- Subsequently, there was an increase of approximately 1 log10 in median HCV-RNA between days 7 and 14 evident in both groups.
Full analysis of the study, including a detailed pharmacokinetic and viral sequencing evaluation, is underway.
“Vertex is committed to developing innovative compounds for the treatment of chronic HCV infection. VX-950, one of the most advanced agents in a promising new class of direct antivirals, underscores that commitment,” said Joshua Boger, Ph.D., Chairman and Chief Executive Officer of Vertex. “The demonstration of antiviral activity in this early clinical study is highly encouraging, and we look forward to sharing these data in greater detail at DDW next week.”
Based on the results of the Phase Ib clinical study, the Company plans to explore the development of VX-950 as monotherapy and in combination with other HCV treatments. Vertex plans to consult with the US FDA and European regulatory authorities on the Company’s development plans.
Vertex expects to file an investigational new drug (IND) application in the second half of 2005 to support Phase II clinical development of VX-950 in the United States. In collaboration with Vertex, Mitsubishi Pharma Corporation is developing VX-950 in Japan and certain Far East countries.
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 principally focused on viral diseases, inflammation, autoimmune diseases and cancer. Vertex co-promotes the HIV protease inhibitor fosamprenavir (Lexiva) with GlaxoSmithKline.