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HIV and Hepatitis.com Coverage of the
46th Annual Meeting of the European
Association for the Study of the Liver

March 30 - April 3, 2011, Berlin, Germany

BMS-790052/BMS-650032 Combo Cures Hepatitis C without Interferon

SUMMARY: Most prior non-responders with HCV genotype 1 achieved sustained response with a quadruple combination containing 2 experimental agents plus pegylated interferon/ribavirin, and nearly 40% did so using only the 2 oral drugs -- BMS-790052 and BMS-650032 -- researchers reported at EASL 2011.

By Matt Sharp

In one of the most exciting studies presented at the European Association for the Study of the Liver conference (EASL 2011) this month in Berlin, 2 new oral agents in combination with standard-of-care hepatitis C treatment showed remarkable results in people with chronic hepatitis C who had not responded to prior standard treatment.

Even more impressive, 4 of 11 patients treated with the 2 oral drugs alone achieved sustained response, offering proof of concept for what doctors and people with hepatitis C virus (HCV) have hoped for a long time: a cure for hepatitis C without the toxic regimen of pegylated interferon/ribavirin.

For a little background, only about 40% of people with difficult-to-treat HCV genotype 1 achieve a sustained virological response (SVR, or a cure) after 48 weeks of pegylated interferon/ribavirin alone. Those who do not respond to a first course of standard-of-care therapy (non-responders) typically do not do well when retreated again with the same regimen. The lowest cure rates are seen in prior null responders, those who do not suppress HCV RNA by at least 2 log IU/mL after 12 weeks of therapy.

The current crop of new direct-acting antiviral drugs are showing more promise for all populations of people with HCV. So far most of these drugs have been added to pegylated interferon/ribavirin, but some are now being tested in all-oral combinations, allowing people with HCV to avoid the side effects of interferon and ribavirin.

In a study presented in Berlin, Anna Lok and colleagues looked at 2 of these direct-acting agents that are thought to be synergistic: BMS-790052, a first-in-class NS5A replication complex inhibitor, and BMS-650032, an HCV protease inhibitor.

The Phase 2a trial, which included 21 genotype 1 null responders, compared 2 arms, one using only 60 mg once-daily BMS-790052 plus 600 mg twice-daily BMS-650032 (Group A) and the second using the 2 new drugs in combination with 180 mcg/week pegylated interferon alfa-2a (Pegasys) and 1000-1200 mg/day weight-adjusted ribavirin (Group B), all for 24 weeks.

About 80% of participants in Group A and 40% in Group B were men. Most were white and the median age was about 55 years. About 90% had the unfavorable CT or TT IL28B gene patterns, which predicts poor response to interferon.

Results were striking especially in the group using the 2 new drugs without standard-of-care therapy. In Group A, 4 of 11 participants (36%) reached SVR at 12 and 24 weeks. As a result, these data show that HCV infection can be cured without interferon and ribavirin.

In the group randomized to receive quadruple therapy, 10 of 10, or 100%, reached SVR at 12 weeks, and 9 of 10 (90%) did so at 24 weeks -- a high cure rate in this difficult-to-treat population. The person who had SVR at 12 but not 24 weeks again showed HCV RNA below the limit of quantification when tested 35 days later.

Resistance to both BMS-790052 and BMS-650032 was seen in the 6 people who had HCV breakthrough. Most adverse events, including fatigue, neutropenia, and ALT elevations, were moderate, and there were no serious adverse events or discontinuations due to adverse events in either group.

Taken together, these results show that BMS-790052 and BMS-650032 are powerful new agents that could change the course of how HCV is treated in the near future.

Another study presented at the conference showed that BMS-790052 plus pegylated interferon/ribavirin was highly effective for people with HCV genotype 1 starting treatment for the first time.

Investigator Affiliations: Medicine, University of Michigan, Ann Arbor, MI; Bristol-Myers Squibb Research and Development, Hopewell, NJ; Alamo Medical Research, San Antonio, TX; The Research Institute, Springfield, MA; University of Colorado-Denver, Aurora, CO; The Liver Institute at Methodist Dallas, Dallas, TX; Carolinas Center for Liver Disease Research Dept, Statesville, NC; Metropolitan Research, Fairfax, VA; Bristol-Myers Squibb Research and Development, Wallingford, CT; Bristol-Myers Squibb Research and Development, Princeton, NJ.

4/12/11

Reference
A Lok, D Gardiner, E Lawitz, et al. Quadruple Therapy with BMS-790052, BMS-650032 and PEG-IFN/RBV for 24 Weeks; Results in 100% SVR12 in HCV Genotype 1 Null Responders. 46th Annual Meeting of the European Association for the Study of the Liver (EASL 2011). Berlin. March 30-April 3. Abstract 418.

Other Source
EASL. Quadruple Therapy Shows 100% Sustained Virological Response (SVR) for HCV Patients Previously Unresponsive to Treatment. Press release. April 2, 2011.





 


 

 


 



 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



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