Patients with hepatitis C virus (HCV) infections that were treated with the novel protease inhibitor, boceprevir, had better virologic responses than patients treated with peginterferon and ribavirin alone, results from two trials published in the New England Journal of Medicine indicated.
Boceprevir is one of two new drugs — the other being telaprevir — currently in development that belongs to a new class of direct-acting antiviral agents that specifically target HCV.
Results from the first trial, HCV RESPOND-2, showed that adding boceprevir to standard two-drug therapy produced a sustained virologic response in patients that previously did not respond to therapy and in those experiencing relapses.
Bruce R. Bacon, MD, of the St. Louis University School of Medicine in Missouri, and colleagues, enrolled 403 patients that tested positive for HCV genotype 1 and assigned them to one of three treatment groups, after a four-week lead-in phase during which all patients were administered peginterferon alfa-2b and ribavirin. Regimens and response rates were as follows:
- Control group (placebo plus peginterferon-ribavirin for 44 weeks) – 7% among previous nonresponders; 29% among patients who had previously relapsed.
- Response-guided boceprevir group (boceprevir plus peginterferon-ribavirin for 32 weeks; patients with detectable HCV RNA at week 8 received interferon-ribavirin for an additional 12 weeks) – 40% among nonresponders; 75% among relapse patients.
- Fixed-duration boceprevir group (boceprevir plus peginterferon-ribavirin for 44 weeks) – 52% in nonresponders; 75% among relapse patients.
Adverse events associated with boceprevir included anemia, rash, dry skin and dysgeusia. Treatment was discontinued in approximately 8% to 12% of these patients.
“This study represents a remarkable advance and a potential cure for people with HCV who have not responded to therapy,” study researchers Stuart C. Gordon, MD, chief in the division of hepatology at Henry Ford Hospital in Detroit, said in a press release, adding that the findings mark “dramatic and rapid” improvements in therapy.
Findings from another study involving boceprevir in patients with previously untreated HCV genotype 1 infection were also impressive.
Fred Poordad, MD of Cedars-Sinai Medical Center in Los Angeles and colleagues, used a similar study design in the SPRINT-2 trial. A 24-week lead-in phase in which peginterferon and ribavirin was initiated before boceprevir or placebo was added to the regimen. Patients were assigned to one of three treatment groups: the standard regimen for an additional 44 weeks, response-guided triple therapy with peginterferon, ribavirin and boceprevir for 24 weeks, and fixed-duration therapy with all three medications for 44 weeks.
Patients in the response-guided group that had undetectable HCV RNA levels between weeks eight and 24 were allowed to discontinue treatment.
In a combined cohort of both black (n=159) and nonblack patients (n=938), sustained virologic responses occurred in 38% of the control group vs. 63% of patients in the response-guided group, and 66% of patients in the triple therapy group assigned to 44 weeks of therapy.
Common adverse events among patients in the boceprevir groups included anemia (49%) and dysgeusia (40%).
In an accompanying editorial Donald M. Jensen, MD, of the Center for Liver Diseases at the University of Chicago Medical Center, pointed out that although the lead-in phase adopted by both studies resulted in advantages including higher rates of sustained virologic responses and lower rates of viral breakthrough during the treatment phases, it could complicate treatment — lengthening the amount of time necessary to measure viral load.
“Future therapy will be more complex, not easier,” Jensen wrote, but added that boceprevir marks a “new era of successful HCV therapy.”
Jensen added that it was important to remember that boceprevir is only effective against HCV genotype 1 and that cirrhosis, which affects “a considerable percentage of patients,” has a negative impact on treatment response.
Additionally, he expressed concerns that HCV may develop resistance to protease-inhibitors, but noted that this usually occurs with monotherapy. “The addition of interferon reduces the rate of emergence of these resistant variants,”Jensen wrote.