R7128 Receives Fast Track Designation From FDA To Treat Chronic Hepatitis C

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Chronic Hepatitis C

Pharmasset has received fast track designation from FDA for R7128 for the treatment of chronic hepatitis C virus (HCV) infection.

R7128 is a prodrug of PSI-6130, an oral cytidine nucleoside analog polymerase inhibitor of HCV that is being developed through Pharmasset's collaboration with Roche. Pharmasset is currently enrolling a 28-day Phase 1 clinical trial to evaluate R7128 in combination with Pegasys (pegylated interferon) plus Copegus(R) (ribavirin) in treatment-naive patients chronically infected with hepatitis C virus (HCV) genotype 1.

Under the FDA Modernization Act of 1997, fast track designation may facilitate the development and expedite the review of a drug candidate that is intended for the treatment of a serious life-threatening condition and demonstrates the potential to address an unmet medical need for such a condition. R7128 was granted the fast track designation primarily due to the need for HCV treatments with novel mechanisms of action, oral administration, different resistance profiles and improved safety and efficacy over the existing standard of care for both treatment-naive and treatment-experienced patients.

"The FDA's fast track designation for R7128 acknowledges the urgent need for new HCV drugs," stated Dr. Michelle Berrey, Pharmasset's Vice President, Clinical Development & Chief Medical Officer. "Currently, there are no HCV polymerase inhibitors approved for the treatment of chronic HCV infection. We continue to work closely with our HCV partner, Roche, and the FDA on the development and regulatory review of R7128, which has demonstrated compelling antiviral activity and has been generally well-tolerated in clinical trials to date."

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R7128 is being developed for the treatment of chronic HCV infection. R7128 is a prodrug of PSI-6130, a pyrimidine nucleoside analog inhibitor of HCV RNA polymerase. A prodrug is a chemically modified form of a molecule designed to enhance the absorption, distribution and metabolic properties of that molecule. Results from an oral single ascending dose study of PSI-6130 in 24 healthy male volunteers showed that PSI-6130 was generally well tolerated with no serious adverse events in doses up to 3000 mg.

R7128 Phase 1 Study Overview

The Phase 1 clinical trial is a multiple center, observer-blinded, randomized and placebo-controlled study to investigate the pharmacokinetics, pharmacodynamics, safety, tolerability and food effect of R7128 in healthy volunteers and in patients chronically infected with HCV genotype 1. This adaptive Phase 1 study is comprised of three parts:

Part 1 is a single ascending dose study of R7128 conducted in 46 healthy volunteers. The primary objective of Part 1 is to assess the safety, tolerability and pharmacokinetics of R7128 following single ascending doses under fasting conditions. The secondary objective of Part 1 is to explore the effect of food on the pharmacokinetics of R7128. Results from the single ascending dose portion of the study indicated that all doses of R7128 studied (500 mg to 9000 mg) were generally safe and well-tolerated. All patients completed the study, and none experienced gastrointestinal adverse events or serious adverse events during the study. No hematological or laboratory abnormalities of clinical significance were noted.

Part 2 is a multiple ascending dose study of R7128 conducted in 40 patients chronically-infected with HCV genotype 1 who previously failed interferon therapy. The primary objective of Part 2 is to assess the safety, tolerability and pharmacokinetics of R7128 after once-daily (QD) or twice- daily (BID) dosing for 14 days. The secondary objective is to assess antiviral activity by measuring the change in HCV RNA. Preliminary data from the multiple ascending dose portion of the study indicated that R7128 demonstrated potent, dose-dependent antiviral activity in four patient cohorts receiving 750 mg or 1500 mg administered either once-daily or twice-daily for 14 days as monotherapy. Patients receiving 1500 mg BID demonstrated a mean 2.7 log10 IU/mL (>99%) decrease in HCV RNA. There was no evidence of viral rebound in any dose cohort during the 14 days of dosing. R7128 was generally safe and well tolerated. There were no serious adverse events, no adverse events requiring dose modification, no dose-related gastrointestinal adverse events and no clinically significant changes in hematologic or other laboratory parameters.

Part 3 is a multi-center, observer-blinded, within-cohort randomized, placebo-controlled study being conducted in up to 75 treatment-naive patients with genotype 1 hepatitis C virus. The primary objective is to assess the safety, tolerability and pharmacokinetics of R7128 in combination with Pegasys plus Copegus. The secondary objective of Part 3 is to evaluate the short-term change in HCV RNA. The study will include two to three oral doses of R7128 (500 mg to 1500 mg) that are being administered twice-daily with Pegasys plus Copegus for 28 days.

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