- Category: Experimental HCV Drugs
- Published on Monday, 19 September 2011 00:00
- Written by Liz Highleyman
Up to 83% of treatment-naive people with difficult-to-treat genotype 1 hepatitis C virus (HCV) infection achieved sustained virological response (SVR) with the experimental HCV NS5A inhibitor BMS-790052 plus pegylated interferon and ribavirin, according to data presented at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2011) this week in Chicago.
BMS-790052 is the first direct-acting antiviral agent that inhibits the HCV NS5A replication complex. The precise function of NS5A is not fully understood, but it appears to play a key role in viral replication, including promoting the activity of the adjacent NS5B polymerase and modulating cell signaling pathways.
Stanislas Pol from Université Paris V (René Descartes) and colleagues conducted a double-blind Phase 2 trial to compare the safety and efficacy of BMS-790052 versus placebo in combination with standard therapy.
The analysis included 48 previously untreated genotype 1 chronic hepatitis C patients. 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 most favorable IL28B gene pattern.
Participants were randomly allocated to receive once-daily BMS-790052 at doses of 3 mg, 10 mg, or 60 mg, or else placebo, along with peginterferon alfa-2a (Pegasys) plus weight-adjusted ribavirin for 48 weeks.
As reported at the EASL conference this past April, 83% of participants in the best-performing (10 mg) BMS-790052 dose arm had extended rapid virological response, or undetectable viral load at both week 4 and week 12, and 92% had sustained response 12 weeks after completing therapy. Researchers presented 24-week SVR data at ICAAC.
- 24-week SVR rates were as follows:
o 3 mg BMS-790052 arm: 42%;
o 10 mg BMS-790052 arm: 83%;
o 60 mg BMS-790052 arm: 83%;
o Placebo arm: 25%.
- At week 48, the overall frequency of serious adverse events, adverse events leading to treatment discontinuation, and specific events of interest were statistically similar in the BMS-790052 and placebo groups.
o 1 patient (about 8%) in the each of the BMS-790052 dose groups experienced serious adverse events, compared with none in the placebo control group.
o 1 patient (about 8%) in the 3 mg and 10 mg BMS-790052 groups, 4 (33%) in the 60 mg group, and 2 (about 17%) in the placebo group discontinued due to adverse events.
o Adding BMS-790052 to pegylated interferon/ribavirindid not lead to apparent increases in blood-related adverse events, liver toxicity, or skin problems.
o 3 people (25%) in the 10 mg and 60 mg BMS-790052 groups, 1 person (8%) in the 3 mg group, and 2 people (17%) in the placebo group required erythropoietin to manage anemia.
"BMS-790052 in combination with [pegylated interferon/ribavirin] achieves higher rates of cure than [pegylated interferon/ribavirin] alone for subjects with HCV genotype 1 infection," the researchers concluded. "Early HCV RNA suppression (i.e. cEVR) may allow early identification of subjects likely to achieve SVR."
Based on these promising findings, Bristol-Myers Squibb indicated that it has started Phase 3 clinical trials of BMS-790052.
Investigator affiliations: Hosp. Cochin, Paris, France; Methodist HS, Dallas, TX; Metro. Research, Fairfax, VA; Research Inst., Springfield, MA; Univ. Colorado, Aurora, CO; Options Health Research, Tulsa, OK; CHU H. Mondor, Creteil, France; Yale, New Haven, CT; Hop. Braboios, Vandoeuvre les Nancy, France; Alabama Liver & Digestive Sp, Montgomery, AL; JJ Peters VAMC, Bronx, NY; Healthcare Research Consult, Tulsa, OK; Mercy Medcal Ctr, Baltimore, MD; Carolinas Ctr. Liver Disease Research, Statesville, CT; BMS, Wallingford, CT.
S Pol, RH Ghalib, VK Rustgi, et al. High Rates of SVR24 for BMS-790052, a NS5A Replication Complex Inhibitor, in Combination with Peg-IFNα-2A and Ribavirin: Phase 2A Trial in Treatment-Naive HCV-Genotype 1 Subjects. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2011). Chicago, September 17-20, 2011. Abstract H1-376.
Bristol-Myers Squibb. BMS-790052 Plus Peginterferon Alfa and Ribavirin Demonstrated up to 83% Sustained Virologic Response 24 Weeks Post-Treatment (SVR24) in Phase II Study of Genotype 1 Hepatitis C Patients. Press release. September 17, 2011.