DDW 2011: Robust Reductions in Serious Liver Complications Likely with New HCV Agent

May 9, 2011
Walter Alexander

Combination treatment with boceprevir produces a significant reduction in incidence of serious liver complications in patients with hepatitis C.

Combination treatment with boceprevir produces a significant reduction in incidence of serious liver complications in patients with hepatitis C.

A model of the likely effects of hepatitis C virus (HCV) treatment including boceprevir plus peginterferon alpha-2b (P) and ribavirin (R) as compared with P/R alone, the standard of care (SOC), projected a 48-59% reduction in the incidence of the serious liver complications in an HCV population in which the SOC had failed, according to Shannon A. Ferrante, PhD, a statistician with Merck Research Laboratories, the manufacturer of boceprevir.

An FDA advisory panel unanimously recommended the approval of boceprevir and telaprevir for the treatment of HCV infections on April 29, 2011. Ferrante noted, in a Digestive Disease Week 2011 poster presentation, that in RESPOND-2, a recent international randomized, multicenter, double-blinded study, treatment with boceprevir plus P/R led to high sustained virologic response (SVR) rates in genotype 1 patients for whom prior treatment with P/R therapy failed. Chronic hepatitis C genotype 1 is the most prevalent and most difficult to treat HCV genotype. To project the long-term clinical impact of treatment with SOC plus boceprevir on patients included in RESPOND-2, Ferrante developed a Markov simulation model to project the lifetime incidence of liver complications in subjects receiving the regimens studied in RESPOND-2. Those who achieved SVR were assumed to be cured of their viral disease.

In RESPONSE-2, SVR rates of 21%, 59% and 66% were reported, respectively, in 403 patients randomized (1:2:2) to SOC, and boceprevir-containing response-guided-therapy (RGT) and fixed-duration-therapy (8 weeks/PR48 weeks). In RGT, boceprevir plus P/R treatment was shortened among those with undetectable HCV virus after the 8th week of treatment. Forty-nine percent of subjects receiving boceprevir-based regimens had undetectable HCV-RNA after 8 weeks of treatment as compared with 9% of subjects in the SOC group.

Ferrante’s model suggested that for every 1000 RESPOND-2 type patients treated with RGT as compared with SOC, 203 cases of compensated cirrhosis, 103 cases of decompensated cirrhosis, 65 cases of hepatocellular carcinoma, 14 liver transplants and 109 liver-related deaths would be prevented. Among patients receiving the boceprevir 8-week/PR 48 week regimen as compared with SOC, 249 compensated cirrhosis cases, 127 decompensated cirrhosis cases, 79 hepatocellular carcinoma cases, 17 liver transplantations, and 134 liver-related deaths would be prevented.

Commenting on Ferrante’s model in an interview, John Vierling, MD, professor of medicine and surgery and chief of hepatology at Baylor College of Medicine, noted, “This is a group that will soon have access to these two direct acting antiviral agents, if the FDA accepts the panel’s recommendations. So the question becomes, ‘How do we factor in all the information at our disposal to project what we’ll encounter?’ And this model shows that regimens with boceprevir would substantially reduce the lifetime incidence of development of liver complications in these treatment failure patients who responded early. The reduction in serious liver complications is robust.” Vierling added, “This type of model is useful, because these therapies will cost more than the SOC therapies, and we need to show where the benefit is substantial enough to warrant treatment.”

Vierling was an investigator in Phase III boceprevir trials.