Roche (SWX: ROG.VX; RO.S, OTCQX: RHHBY) and InterMune, Inc. (NASDAQ: ITMN) announced that the first patient has been dosed in a Phase 2b study evaluating the hepatitis C virus (HCV) protease inhibitor, R7227/ ITMN-191, in combination with PEGASYS® (pegylated interferon alfa- 2a) and COPEGUS® (ribavirin). The study, to be conducted at 45 sites globally, will further define the safety and efficacy profile of R7227/ ITMN-191, for a treatment duration of up to 24 weeks. Approximately 300 treatment-naïve patients chronically infected with HCV genotype 1 - the most difficult to treat form of the virus -will participate. R7227/ 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' Clinical Development for Virology, said, "his 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, "e are very pleased to announce with our colleagues, Roche, the start of the global Phase 2b program of R7227/ ITMN‐191 in treatment‐naïve HCV patients. This study will significantly expand the clinical efficacy and safety database for R7227/ 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 R7227/ 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 R7227/ 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 R7227/ 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 R7227/ 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.

R7227/ ITMN191 - Next Steps in Development Program

Roche and InterMune will also initiate in the third quarter a Phase 1 trial combining R7227/ ITMN‐191 with low dose ritonavir to examine the virologic effect of ritonavirboosted R7227/ 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 R7227/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 R7227/ ITMN‐191 regimens administered with PEGASYS and ribavirin for 14 days.

Frank Duff commented, "ombining R7227/ 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."R7227/ ITMN‐191 is also being investigated in combination with the NS5B polymerase inhibitor R7128 in the INFORM‐1 study. This innovative study has recently been expanded to examine regimens in which both R7227/ ITMN‐191 and R7128 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.

Notes

* Patients who achieve RVR, defined as undetectable viral levels (less than 15 IU/mL) by the end of week 4, will stop all treatment at week 24 and will be followed post treatment to evaluate whether they achieve SVR. Patients in the treatment arms who do not achieve RVR will continue with PEGASYS and COPEGUS treatment for a total duration of 48 weeks.

† As in Part 1, patients who achieve RVR by the end of week 4 will stop all treatment at week 24 and will be followed post treatment to evaluate whether they achieve SVR. Patients who do not achieve RVR will continue with PEGASYS and COPEGUS treatment for a total of 48 weeks.

About R7227/ ITMN191

R7227/ ITMN‐191 is a potent, macrocyclic inhibitor of HCV NS3/4A protease activity, and has produced multi‐log10 reductions in HCV levels in chronic HCV patients, when administered for 14 days as monotherapy. When R7227/ ITMN‐191 is combined with PEGASYS and COPEGUS, or the NS5B polymerase inhibitor R7128, it reduced viral loads below the limit of detection in a majority of study‐treated patients. R7227/ ITMN‐191 was safe and well tolerated in these studies.

About PEGASYS

PEGASYS, in combination with COPEGUS (ribavirin), is indicated for the treatment of adults with chronic HCV who have compensated liver disease and have not previously been treated with interferon alpha. Efficacy has been demonstrated in patients with compensated liver disease and histological evidence of cirrhosis (Child‐Pugh class A) and patients with HIV disease that are clinically stable (e.g., antiretroviral therapy not required or receiving stable antiretroviral therapy). In addition, PEGASYS in combination with COPEGUS is the first and only FDAapproved regimen for the treatment of chronic HCV in patients coinfected with HCV and HIV. PEGASYS is the only pegylated interferon indicated for the treatment of adult patients with chronic hepatitis B (HBeAg positive and HBeAg negative chronic hepatitis B who have compensated liver disease and evidence of viral replication and liver inflammation). PEGASYS is dosed at 180mcg as a subcutaneous injection taken once a week. COPEGUS is available as a 200mg tablet, and is administered orally two times a day as a split dose. Roche has backed PEGASYS with the most extensive clinical research program ever undertaken in HCV, with major studies initiated to advance treatment for HCV patients with unmet needs, including patients co‐infected with HIV and HCV, African Americans, patients with cirrhosis, and patients who have failed to respond to previous therapy.

Source
Roche

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