Triple drug combo works against HCV genotype 1 infection with or without cirrhosis

Last Updated: 2015-05-05

By Megan Brooks

NEW YORK (Reuters Health) - An all-oral fixed-dose combination of daclatasvir, asunaprevir, and beclabuvir is highly effective in patients with chronic hepatitis C virus (HCV) genotype 1 infection with or without cirrhosis, according to two studies published today in JAMA.

The UNITY-1 and UNITY-2 studies "add to the armamentarium of all-oral interferon-free regimens that have revolutionized management of hepatitis C, not only for patients who are treatment naive with no significant liver disease but also for those who are treatment experienced and those with cirrhosis," writes Dr. Hari Conjeevaram, of the University of Michigan, Ann Arbor, in an accompanying editorial.

Of the seven HCV genotypes, genotype 1 is the most common worldwide, accounting for roughly 60% of infections.

In the UNITY-1 study, 415 noncirrhotic patients with HCV genotype 1 received a twice-daily, fixed-dose combination of daclatasvir (30 mg), asunaprevir (200 mg) and beclabuvir (75 mg) (DCV-TRIO regimen) for 12 weeks and were then followed for up to 24 weeks after treatment.

Overall, 379 of 415 patients (91.3%) achieved sustained virologic response (SVR) defined as HCV-RNA <25 IU/ml at post-treatment week 12. SVR12 was achieved in 287 of 312 treatment-naive patients (92%) and 92 of 103 treatment-experienced patients (89.3%). Virologic failure occurred in 8% of patients.

The most common adverse events (seen in at least 10% of patients) were headache, fatigue, diarrhea, and nausea, report Dr. Fred Poordad of the University of Texas Health Science Center, San Antonio, and colleagues.

"This study demonstrates that 12 weeks of therapy with the DCV-TRIO regimen without ribavirin was associated with high rates of SVR12 in patients with HCV genotype 1 infection," they note.

In the UNITY-2 study, 202 cirrhotic patients with HCV genotype 1 received the DCV-TRIO regimen for 12 weeks, with either weight-based ribavirin (1,000-1,200 mg/d) or matching placebo, with 24 weeks follow-up after completion of treatment.

In the 112 treatment-naive patients, SVR12 was achieved by 93% of patients receiving DCV-TRIO alone and by 98% of patients with ribavirin added. The corresponding SVR12 rates in the 90 treatment-experienced patients were 87% and 93%.

"We are looking for a 90% threshold for hepatitis C treatment these days and it was nice to see that even in this group of patients with cirrhosis we could achieve those kinds of levels," first author Dr. Andrew Muir, of Duke University Medical Center in Durham, North Carolina, noted in a JAMA podcast.

In this study, patients were stratified according to HCV genotype 1 subtype (1a or 1b). Fifty-one of 52 (98%) patients with genotype 1b infection achieved SVR12 overall. Among patients with genotype 1a infection, SVR12 was achieved by 88% of those receiving DCV-TRIO alone and by 95% of those who added ribavirin.

"However, the contribution of ribavirin to SVR12 remains uncertain because of the small sample sizes; results suggest that inclusion of ribavirin with the regimen may be considered for patients with genotype 1a infection," the authors note.

The role of the ribavirin is the "other interesting point here," Dr. Muir commented. "This is a medicine we have used for many years and we don't have a full understanding of its role and its mechanism and although we do not have statistical power to really comment, there is a suggestion here that ribavirin raises the response rate and gets us to those high levels that we are looking for."

In his editorial, Dr. Conjeevaram notes that, "Despite the progress and the success of viral eradication, numerous questions remain unanswered such as response based on race, still difficult-to-treat situations such as patients with end-stage liver disease or undergoing hemodialysis, access to and affordability of these therapies, improvement in quality of life, and cost-effectiveness. It is time to reflect on these challenges and find solutions because the influence of HCV infection on global society is an ongoing challenge."

Both studies were funded by Bristol-Myers Squibb. Several authors have disclosed relationships with the company and other pharmaceutical companies, which are listed with the original article.

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JAMA 2015.