The 63rd Annual Meeting of the American Association for the Study of Liver Disease (AASLD) featured updates from several pharmaceutical companies developing new drugs to be used in combination for hard-to-treat patients with the hepatitis C virus (HCV). It was held in Boston, MA, on November 9-13, 2012.
The standard treatment for HCV, weekly injections of pegylated interferon and a daily ribavirin oral pill, is not ideal. Nearly half of patients do not respond to it. Further, patients often experience debilitating side effects that can last the duration of the treatment, either 24 or 48 weeks. In contrast, the newer HCV drugs and combination therapies covered during the AASLD meeting were largely interferon-sparing, eliminating the main cause of the side effects.
Gilead Sciences, Inc., based in Foster City, CA, presented findings of its ELECTRON study of 25 patients with genotype 1 chronic HCV. People with this genotype account for approximately 70% of patients. For 12 weeks, subjects were treated with a combination of three oral drugs: sofosbuvir (a polymerase inhibitor), ribavirin and GS-5885. One of a new class of drugs called NS5A inhibitors, GS-5885 blocks the replication of HCV. Gilead reported that the virus was undetectable four weeks after the patients completed therapy. Although the drugs were well tolerated overall, sofosbuvir and GS-5885 are still being studied for safety and efficacy.
Further, Gilead will initiate a Phase III clinical trial evaluating a combination therapy of sofosbuvir/GS-5885 in genotype 1 patients who have not previously received the drugs. Investigators will evaluate the fixed-dose combination with and without ribavirin for 12 and 24 weeks in 800 patients.
Germany-based Boehringer Ingelheim reported new data from the SOUND-C2, a mid-stage clinical trial. The study measured the efficacy of a combination of three oral drugs: BI-201335, a protease inhibitor; BI-207127, a polymerase inhibitor; and ribavirin. The results showed that 69% of HCV patients in the study were free of the virus at 12 and 24 weeks following the end of treatment. The company will initiate a late-stage clinical trial of the therapy.
Bristol-Myers Squibb, headquartered in New York City, presented results from a 16-patient clinical study of its combination of three oral drugs: daclatasvir (NS5A inhibitor), asunaprevir (a protease inhibitor) and BMS-791325 (a non-nucleoside polymerase inhibitor). Data showed that 94% of HCV patients cleared the virus. Final stage clinical studies will begin in 2014.
Bristol-Myers also reported results from a trial of 18 patients who had previously been treated with interferon, but unsuccessfully. The patients received 12 weeks of daclatasvir and asunaprevir therapy. In all, 78% had no detectible levels of the virus 12 weeks after completing the therapy. The company is seeking approval in Japan, where a subset of patients who respond best to the combination are found.
Sources: Reuters.com, November 10, 2012 and Bloomberg.com, November 12, 2012