BMS-790052 + Pegylated Interferon/Ribavirin Works Well for First HCV Treatment

SUMMARY: About 90% of treatment-naive genotype 1 hepatitis C patients achieved sustained response at 12 weeks post-treatment using the experimental HCV protease inhibitor BMS-790052 plus pegylated interferon/ribavirin, researchers reported at EASL 2011.

By Liz Highleyman

People with chronic hepatitis C Virus (HCV) infection undergoing treatment for the first time have the greatest likelihood of achieving sustained virological response (SVR), or continued undetectable HCV viral load after completing therapy.

Nevertheless, only about half of people with hard-to-treat HCV genotype 1 are cured the first time. New direct-acting antiviral drugs that target various steps of the HCV lifecycle increase the chances of treatment success when added to standard-of-care therapy -- pegylated interferon plus ribavirin -- and may shorten treatment duration.

In a late-breaker poster presented at the European Association for the Study of the Liver conference (EASL 2011) this month in Berlin, Stanislas Pol from Hôpital Cochin in Paris and colleagues described a study looking at 3 doses of BMS-790052 combined with standard therapy.

This Phase 2a trial included 48 genotype 1 chronic hepatitis C patients undergoing treatment for the first time. About two-thirds were men and the median age was about 50 years. About 80% were white, two-thirds had HCV genotype 1a, and about one-third had the favorable IL28B CC gene pattern (though this varied across study arms).

Participants were randomly assigned to received BMS-790052 at doses of 3 mg, 10 mg, or 60 mg once-daily in combination with pegylated interferon alfa-2a (Pegasys) plus weight-based ribavirin, or else standard therapy alone, all for 48 weeks.

Results

	In an intent-to-treat analysis at 4 weeks, 42% of patients taking BMS-790052 3 mg, 92% taking 10 mg, and 83% taking 60 mg achieved rapid virological response (RVR), compared with 8% in the standard therapy control group.
	At 12 weeks, 42%, 83%, and 75% of patients, respectively, in the 3 BMS-790052 dose arms still had undetectable viral load, compared with 8% in the standard therapy arm.
	Sustained virological response rates 12 weeks after completing therapy (SVR12) were again 42% (5 of 12), 92% (11 of 12), and 83% (10 of 12), respectively, in the BMS-790052 arms, while the standard therapy arm rose to 25% (3 of 12).
	Participants in the BMS-790052 10 mg and 60 mg arms had similar response rates regardless of IL28B genotype.
	2 people experienced on-treatment HCV breakthrough or post-treatment relapse in the BMS-790052 60 mg arm, compared with 3 in the 10 mg arm, 7 in the 3 mg arm, and 9 in the standard therapy arm.
	BMS-790052 was generally well-tolerated, with overall adverse event rates similar to those seen with standard therapy.
	However, treatment interruptions, drug discontinuations, and dose reductions were more likely in the highest BMS-790052 dose group.

Based on these findings, the researchers concluded, "BMS-790052 is a potent HCV replication complex inhibitor and can achieve high rates of SVR at week 12 in HCV genotype 1-infected patients" when combined with pegylated interferon/ribavirin.

Sustained response rates were high with BMS-790052 at doses of 10 mg (92%) or 60 mg (83%), they added, but the lowest dose was not as effective.

Another study presented at the conference showed that BMS-790052 plus a second direct-acting drug, BMS-650032, cured most prior non-responders when used in a quadruple regimen with pegylated interferon/ribavirin, and nearly 40% when the 2 oral drugs were used alone.

Investigator affiliations: Hôpital Cochin, Paris, France; Liver Institute at Methodist Health System, Dallas, TX; Metropolitan Research, Fairfax, VA; The Research Institute, Springfield, MA; University of Colorado, Aurora, CO; Options Health Research, LLC, Tulsa, OK; CHU Henri Mondor, Creteil, France; Yale University School of Medicine, New Haven, CT; Hopitale Adultes de Braboios, Vandoeuvre les Nancy, France; Alabama Liver & Digestive Specialists, Montgomery, AL; James J Peters VAMC, Bronx, NY; Healthcare Research Consultants, Tulsa, OK; Mercy Medical Center, Baltimore, MD; Carolinas Center for Liver Disease Research Dept, Statesville, NC; Bristol Meyer Squibb Co., Wallingford, CT.

4/12/11

Reference

S Pol. RH Ghalib, VK Rustgi, et al. First report of SVR12 for a NS5A replication complex inhibitor, BMS-790052 in combination with peg-IFN-alfa-2a and RBV: phase 2a trial in treatment-naive HCV-genotype 1 subjects. 46th Annual Meeting of the European Association for the Study of the Liver (EASL 2011). Berlin. March 30-April 3. Abstract 2.

Other Source
Bristol-Myers Squibb Company. Investigational Direct-Acting Antiviral BMS-790052 Plus PEG-Interferon Alfa and Ribavirin Achieved Up to 92% Sustained Virologic Response in Phase II Dose-Ranging Study of Treatment-Naive Hepatitis C Patients. Press release. March 31, 2011.