WASHINGTON – Results from a planned interim analysis show that using a combination of simeprevir and sofosbuvir as hepatitis C therapy achieved slightly higher sustained viral response in HCV genotype 1–infected patients at 4 and 12 weeks post treatment, suggesting that it may not be necessary to add in ribavirin.

That’s according to lead author Dr. Ira M. Jacobson, medical director of the Center for the Study of Hepatitis C at the Weill Cornell Medical College, New York, who spoke at the annual meeting of the American Association for the Study of Liver Diseases.

Dr. Jacobson presented results from the four-arm, two-cohort, phase IIa COSMOS (Combination of Simeprevir and Sofosbuvir in HCV Genotype 1–Infected Patients) study. He reported on the final sustained viral response (SVR)12 for both arms of cohort 1 and the interim SVR4 for the 12-week arms of cohort 2. The two cohorts were enrolled simultaneously.

Patients were randomized to simeprevir 150 mg once daily plus sofosbuvir 400 mg once daily either with or without ribavirin for 12 or 24 weeks. Simeprevir is an investigational NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir. Sofosbuvir is an investigational nucleotide inhibitor developed by Gilead Sciences.

Cohort 1, with 80 patients, had a METAVIR score of F0-F2 and had previously not responded to pegylated interferon plus ribavirin. METAVIR is an algorithm for establishing degree of fibrosis, with 0 being no fibrosis and 4 being cirrhosis. There were four arms of cohort 1: 24 patients received the triple drug regimen for 24 weeks, 15 received simeprevir plus sofosbuvir for 24 weeks, 27 received the triple therapy for 12 weeks, and 14 were given simeprevir plus sofosbuvir for 12 weeks.

Cohort 2, with 87 patients, consisted of treatment-naive or prior null responders and those with a METAVIR score of F3-F4. In the four arms studied, 30 received triple therapy for 24 weeks, 16 received simeprevir plus sofosbuvir for 24 weeks, 27 got triple therapy for 12 weeks, and 14 received simeprevir plus sofosbuvir for 12 weeks. There was an even split in each arm between treatment-naive and null responders.

At the planned interim analysis, all patients in both cohorts had completed 12 weeks of therapy. In cohort 1, all patients – with the exception of three in the first arm and one in the second arm – had completed 24 weeks of therapy. All cohort 2 patients were continuing on study drugs, with the exception of two patients who discontinued triple therapy and one who stopped taking the combination of simeprevir plus sofosbuvir.

In cohort 1, 96% of those who took triple drug therapy for 12 weeks achieved an SVR12, compared with 93% of those on the dual-drug regimen. The SVR12 in those who received 24 weeks of therapy was 79% for triple therapy and 93% for dual therapy.

For cohort 2, the SVR4 for dual therapy was 100% after 12 weeks of treatment, compared with 96% for the triple therapy. All treatment-naive patients achieved an SVR4 while taking either triple or dual therapy. All prior null responders taking dual therapy also achieved an SVR4, while only 93% of those on the triple therapy achieved an SVR4.

When looked at by HCV GT1 subtype, the results show that patients with the Q80K polymorphism did not fare as well. In cohort 1, 89% of patients with that polymorphism achieved an SVR12, compared with 100% of those with GT1a or 1b without Q80K. In cohort 2, 91% of those with the polymorphism achieved an SVR4, compared with 100% of the patients with GT1a or 1b who did not have Q80K.

The most common adverse events were fatigue, headache, and nausea. Adverse events occurred in 70% of patients in the 12-week treatment group and 90% in the 24-week group. Three patients had a serious adverse event.

In late October, the Food and Drug Administration’s Antiviral Drugs Advisory Committee unanimously backed simeprevir for approval in combination with pegylated interferon and ribavirin for chronic HCV GT1 infection in adults with compensated liver disease, including cirrhosis, who are treatment naive or have failed previous interferon-based therapy. The FDA advisers said that the simeprevir regimen would likely be easier to manage than the first-generation protease inhibitors currently approved for treating chronic HCV, telaprevir and boceprevir, which require 6-12 pills daily.

The agency is expected to rule on simeprevir’s approval by Nov. 27.

Janssen paid for the study. Dr. Jacobson reported that he receives grants or research support from, serves on the speakers bureaus of, or acts as a consultant to AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, and other companies.

aault@frontlinemedcom.com

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COSMOS: Simeprevir plus sofosbuvir elicits sustained viral response