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Roche and InterMune Begin Phase 2b Trial of HCV Protease Inhibitor RG7227/ITMN-191

Roche and InterMune announced on August 19, 2009 that they had started treating the first patient in a Phase 2b clinical trial of an experimental hepatitis C virus (HCV) protease inhibitor they are jointly developing. The compound's Roche designation is RG7227 (formerly R7227), while the InterMune designation is ITMN-191. The trial is evaluating the safety and efficacy of RG7227/ITMN-191 in combination with pegylated interferon plus ribavirin in treatment-naive genotype 1 chronic hepatitis C patients.

Below is an excerpt from a joint press release describing the new trial.

Roche and InterMune Initiate Phase 2b Clinical Trial of RG7227/ ITMN-191 in Patients With Chronic Hepatitis C Patients With Chronic Hepatitis C

Study will further define the safety and efficacy profile
Parallel Phase 1 trial will assess ritonavir-boosted dosing
INFORM-1 study with polymerase inhibitor RG7128 ongoing

Basel, Switzerland and Brisbane, Calif. -- August 19, 2009 -- 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 (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 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, MD, 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 and 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.

About RG7227/ITMN-191

RG7227/ 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 RG7227/ITMN-191 is combined with Pegasys and Copegus, or the NS5B polymerase inhibitor RG7128, it reduced viral loads below the limit of detection in a majority of study-treated patients. RG7227/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 FDA-approved 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 180 mcg 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.

About Roche

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world's largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche's personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2008, Roche had over 80,000 employees worldwide and invested almost 9 billion Swiss francs in R&D. The Group posted sales of 45.6 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan.

For more information: www.roche.com.

About InterMune

InterMune is a biotechnology company focused on the research, development and commercialization of innovative therapies in pulmonology and hepatology. InterMune has a pipeline portfolio addressing idiopathic pulmonary fibrosis (IPF) and hepatitis C virus (HCV) infections. The pulmonology portfolio includes the completed Phase 3 CAPACITY program, now in pre-registration, which evaluated pirfenidone for the treatment of patients with IPF; RECAP, an open-label extension study from CAPACITY and a research program focused on small molecules for the treatment of pulmonary disease. The hepatology portfolio includes the HCV protease inhibitor compound RG7227/ ITMN-191 in Phase 2b, a second-generation HCV protease inhibitor research program, and a research program evaluating new targets in hepatology.

For additional information about InterMune and its R&D pipeline, please visit www.intermune.com.

9/04/09

Source
Roche and InterMune. Roche and InterMune Initiate Phase 2b Clinical Trial of RG7227/ ITMN-191 in Patients With Chronic Hepatitis C Patients With Chronic Hepatitis C. Press release. August 19, 2009.