Weekend ReadingToday you're in for treat, sit back and listen to Dr. Gregory T. Everson, one of the country's leading hepatologist discuss his manuscript; "Efficacy of an Interferon- and Ribavirin-Free Regimen of Daclatasvir, Asunaprevir, and BMS-791325 in Treatment-Naive Patients With HCV Genotype 1 Infection."
The Phase II study is exciting folks, up to 94% treatment-naive genotype 1 participants achieved SVR12 using the triple-antiviral combination without interferon or ribavirin, currently Phase III clinical trials are underway which included treatment-experienced, naive and patients with cirrhosis.
In Case You Missed It - Published on Jan 15, 2014
Dr. Gregory T. Everson discusses his manuscript "Efficacy of an Interferon- and Ribavirin-Free Regimen of Daclatasvir, Asunaprevir, and BMS-791325 in Treatment-Naive Patients With HCV Genotype 1 Infection."
To view abstract http://bit.ly/1astcIL.
Triple-antiviral therapy achieves 94% response without interferon, ribavirin
By: MICHELE G. SULLIVAN
Both a 12-week and a 24-week regimen of three oral antiviral drugs achieved sustained viral remissions at 12 weeks in up to 94% of treatment-naive patients with genotype 1 hepatitis C virus infections.
The three oral antivirals included daclatasvir, an NS5A replication complex inhibitor; asunaprevir, an NS3 protease inhibitor; and BMS-791325, an investigational selective non-nucleoside polymerase inhibitor. A key point of the study is its proof that short-duration treatment – even without interferon or ribavirin – can result in sustained remission, Dr. Gregory T. Everson and his colleagues wrote in the February issue of Gastroenterology (doi.org/10.1053/j.gastro.2013.10.057).
"Shorter treatment durations are preferable because they may improve patient compliance. In this study, treatment periods of both 12 and 24 weeks yielded high SVR (sustained viral remission) rates, suggesting no advantage for extending treatment duration to 24 weeks."
Further, the triple-antiviral combination apparently controlled viral replication without using interferon or ribavirin, thus avoiding their side effects. The current regimen for treatment-naive patients with genotype 1 hepatitis C virus infections calls for a 48-week treatment with peginterferon and ribavirin with telaprevir or boceprevir.
"Ribavirin contributes to anemia and it is teratogenic; thus, effective treatments without ribavirin are desirable," wrote Dr. Everson of the University of Colorado, Denver, and his coauthors. "This interferon- and ribavirin-free regimen did not alter hemoglobin levels in a clinically meaningfully manner, as evidenced by no grade 1 or higher hemoglobin reductions and no adverse events of anemia."
Dr. Everson and his colleagues gave the regimen for periods of 12 and 24 weeks and with two different doses of BMS-791325, resulting in a four-way randomized study. Groups 1 and 2 were treated for 12 weeks with the combination of daclatasvir 60 mg once daily, asunaprevir 200 mg twice daily, and BMS-791325 (twice daily 75 mg or 150 mg). Groups 3 and 4 had exactly the same two-treatment regimen, but took the drugs for 24 weeks. After treatment, there was a 48-week follow-up period.
Among the 66 patients in the study, the average age was about 50 years old, and the mean HCV-RNA level was 6 log10 IU/mL. Most (75%) had HCV genotype 1a; the rest had 1b. All were treatment naive. Four patients withdrew before the study’s end; none of the withdrawals were for adverse events.
In groups 1 and 2 (75 mg BMS-791325, twice daily for 12 and 24 weeks), the viral load decreased rapidly. By week 4, all of these patients achieved a HCV-RNA level of less than 25 IU/mL; 97% maintained that level through the end of treatment. In a modified intent-to-treat analysis, 94% achieved a sustained viral response by week 12.
In groups 3 and 4 (150 mg BMS-791325, twice daily for 12 or 24 weeks), HCV-RNA levels also fell rapidly in the first month, By week 4, all of those in the 12-week group and all but one in the 24-week group had levels of less than 25 IU/mL, which were sustained through the end of treatment. In the intent-to-treat analysis, 91% overall had an HCV-RNA load of less than 25 IU/mL by the end of treatment.
Overall, there were three treatment failures: one each in groups 3 and 4 had viral breakthrough, and one in group 4 experienced a relapse at week 4.
Both breakthrough patients were given peginterferon-alfa/ribavirin in addition to the direct-acting antivirals. After 16 weeks, one discontinued treatment because of interferon-related cerebral vasoconstriction. That patient had an undetectable HCV-RNA level at the end of treatment, but relapsed by post treatment week 4. The other patient had a sustained viral response.
The study was sponsored by Bristol-Myers Squibb. Dr. Everson listed financial and research relationships with numerous pharmaceutical companies, including Bristol-Myers. His coauthors also declared relationships with numerous drug manufacturers, including Bristol-Myers.
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HCV Genotypes and Treatment
News and research is offered on this page with a focus on treatment options for HCV genotypes 1-6, including FDA approved drugs, and investigational agents currently in clinical trials. Information is extracted from news articles, peer-reviewed journals, as well as liver meetings/conferences, research manuscripts and interactive learning activities.
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