FDA committee unanimously supports boceprevir for HCV genotype-1

An FDA advisory committee voted unanimously for the use of boceprevir for the treatment of chronic hepatitis C virus genotype-1 infection combined with peginterferon alfa and ribavirin in adult patients with compensated liver disease previously untreated or who have failed previous therapy.

The available data support approval of boceprevir (Victrelis, Merck), the new drug application 202-258 and HCV protease inhibitor. They recommend a dosage of boceprevir 500 mg every 7 to 9 hours with food.

“This is going to be a real game-changer for our hepatitis C practices, and I can’t wait to get back and to talk to my patients about it,” Barbara H. McGovern, MD, of the division of infectious diseases at Tufts University School of Medicine, said during the FDA committee meeting. “I do urge the sponsor to move on with the trials in coinfection because some of my patients are HIV coinfected and I would very much like to know how to approach that patient subset. It will also be very important to see how this drug — the triple-therapy paradigm — will play out in the community.”

As previously reported in Infectious Disease News, data from the HCV RESPOND-2 trial and the SPRINT-2 trial suggest that the addition of boceprevir to peginterferon-ribavirin treatment resulted in significantly higher rates of sustained virologic response in patients previously treated and patients with previously untreated HCV genotype-1.

In presenting the phase 3 study results, Laurie J. MacDonald, MD, an ID physician from Merck, said the addition of boceprevir produced superior sustained virologic response rates compared with the standard of care in both treatment-naive and treatment-failure patients. Both the 28- and 48-week treatments were significantly more effective than peginterferon-ribavirin alone. In addition, boceprevir increased sustained virologic response in all subgroups, including patients with poor interferon response.

“When interferon was approved in 1991, we had sustained responses in 10%, and for the past 5 or 6 years, we’ve had an overall sustained response rate of 45% for genotype-1 and 55% overall. Now to go to 70% seems like a dream come true for those of us who have been in this field,” said Lawrence Friedman, MD,of the department of medicine at Newton-Wellesley Hospital in Newton, Mass.

Janice K. Albrecht, PhD, also a Merck representative, recommended response-guided therapy regimen for both treatment-naive and treatment-failure patients, allowing the early responder to receive a shorter duration of therapy with efficacy equal to adding boceprevir to the standard peginterferon-ribavirin 48-week regimen. “Using [response-guided therapy], 44% of patients received only 28 weeks of treatment and achieved a [sustained virologic response] rate of 96%,”she said.

Adverse events included anemia (occurred in 52%), neutropenia, and thrombocytopenia.

“We’ve become very comfortable dealing with the anemia issues from peginterferon and ribavirin, so there will be a little more of it, but we can handle it,” Friedman said.

Unknown drug interactions were of concern. “I would urge the sponsor to complete those drug interaction studies as quickly as possible,” Michelle E. Roland, MD, chief of the Office of AIDS at the California Department of Public Health, said during the meeting.

Although the FDA is not required to follow the recommendations of the advisory committee, it usually does.

The FDA approval of telapravir and bocepravir marks a new chapter in the treatment of Hepatitis C.

This disease has historically been very difficult to treat, with 40 – 50% sustained virological response (SVR) to therapy under the best of circumstances. The availability of these new agents is very exciting as the SVR rates are in excess of 70% when these new agents are used in combination with pegylated interferon and ribavirin. Telapravir has also been shown to have efficacy in the treatment of relapsers and non-responders, a particularly difficult group of patients to treat, and has been approved by the FDA for these indications. A shorter treatment duration of 24 weeks for most patients is also a welcome change from the 48 weeks of therapy required for most patients with pegylated interferon and ribavirin alone regimens. There are however limitations that must be recognized: These medications are to be used in combination with pegylated interferon and ribavirin and hence do not eliminate the well known and dreaded side effects of these medications. In fact we will need to contend with additional side effects such as increased incidences of rash, anemia, dysguesia and rectal irritation with these new drugs.

Other issues include drug resistance to this new class and problems with patient medication compliance as patients will now have to take more pills and with greater frequency. All things considered however, the advent of these new drugs is reminiscent of the era of the highly active antiretrovirals in the treatment of HIV and have the potential to be major game changers in the treatment of HCV.

– Varsha Moudgal, MD, FACP, FIDSA

Infectious Diseases Fellowship program director,

Saint Joseph Mercy Hospital

Disclosure: Dr. Moudgal reports no relevant financial disclosures.

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