Roche (SIX: ROG.VX; RO.S, OTCQX: RHHBY) and InterMune, Inc. (Nasdaq: ITMN) today announced that the first patient has been dosed in a Phase 2b study evaluating the hepatitis C virus (HCV) protease inhibitor, RG7227/ ITMN-191, in combination with PEGASYS(R) (pegylated interferon alfa-2a) and COPEGUS(R) (ribavirin). The study, to be conducted at 45 sites globally, will further define the safety and efficacy profile of RG7227/ ITMN-191, for a treatment duration of up to 24 weeks. Approximately 300 treatment-naive patients chronically infected with HCV genotype 1 - the most difficult to treat form of the virus - will participate.
RG7227/ ITMN-191 is being developed in partnership by Roche and InterMune. Initiation of the Phase 2b trial triggered a $20 million event payment from Roche to InterMune under the companies' collaboration agreement.
Frank Duff, M.D., Head of Roche's Clinical Development for Virology, said, "This trial represents an important step forward in the development of this oral direct-acting antiviral (DAA), and builds on the encouraging clinical safety and efficacy data generated to date."
Dan Welch, Chairman, Chief Executive Officer and President of InterMune, said, "We are very pleased to announce with our colleagues, Roche, the start of the global Phase 2b program of RG7227/ ITMN-191 in treatment-naive HCV patients. This study will significantly expand the clinical efficacy and safety database for RG7227/ ITMN-191, and in the first quarter of next year provide our first look at the rapid virologic response (RVR) rates associated with this triple therapy."
Phase 2b Triple Combination Trial Design
The objective of the Phase 2b randomized, double-blind, placebo-controlled study is to further characterize the safety, tolerability, and antiviral effects of RG7227/ ITMN-191 in triple combination, compared with standard of care (PEGASYS plus COPEGUS).
The two-part study will evaluate treatment regimens of both 12 and 24 weeks. In Part 1 of the study, approximately 210 patients will be randomized to one of four study arms - three of which will receive a 12-week regimen of RG7227/ ITMN-191 at either 300 mg every 8 hours, 600 mg every 12 hours or 900 mg every 12 hours, in combination with PEGASYS and COPEGUS, followed by 12 weeks of therapy with PEGASYS and COPEGUS.* The fourth group will be a control arm receiving PEGASYS and COPEGUS dosed for 48 weeks.
Part 2 of the study, which is expected to begin in the first quarter of 2010, will further evaluate RG7227/ ITMN-191 in a 24-week triple combination regimen with PEGASYS and COPEGUS. Approximately 90 patients will be randomized to one of two study arms in Part 2, either a 24-week regimen of RG7227/ ITMN-191 in combination with PEGASYS and COPEGUS, or a control arm of PEGASYS and COPEGUS dosed for 48 weeks.** Dose selection for Part 2 will be informed by week 4 results generated in Part 1.
RVR results from Part 1 of the study are expected in the first quarter of 2010.
RG7227/ ITMN-191 - Next Steps in Development Program
Roche and InterMune will also initiate in the third quarter a Phase 1 trial combining RG7227/ ITMN-191 with low dose ritonavir to examine the virologic effect of ritonavir-boosted RG7227/ ITMN-191 in once-daily and twice-daily regimens in combination with standard dosing of PEGASYS and COPEGUS in patients chronically infected with HCV genotype 1.
This study builds on promising drug-drug interaction data recently generated in healthy volunteers; a low dose of ritonavir significantly improved RG7227/ ITMN-191 AUC and plasma concentrations at later times. There were no remarkable safety findings.
The Phase 1 study will evaluate the safety, tolerability, pharmacokinetics and antiviral activity of once-daily and twice-daily ritonavir-boosted RG7227/ ITMN-191 regimens administered with PEGASYS and ribavirin for 14 days.
Dr. Duff commented, "Combining RG7227/ ITMN-191 with low dose ritonavir has the potential to deliver additional benefits to patients, including the requirement for less frequent dosing and fewer tablets per day. Data generated from this Phase 1 trial may pave the way for larger studies investigating this treatment combination."
RG7227/ ITMN-191 is also being investigated in combination with the NS5B polymerase inhibitor RG7128 in the INFORM-1 study. This innovative study has recently been expanded to examine regimens in which both RG7227/ ITMN-191 and RG7128 are dosed twice daily in treatment-experienced patients. Results from all cohorts of this study will be presented in an oral presentation in Presidential Plenary Session III on the morning of November 3 at the 2009 AASLD meeting. Additional abstracts regarding pharmacokinetic/pharmacodynamics and resistance have been accepted for poster presentation.