FDA approves boceprevir for hepatitis C

FDA has approved boceprevir (Victrelis, Merck) for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin, in adult patients aged 18 years and older with compensated liver disease. This indication includes patients with cirrhosis who are previously untreated or who have not responded to previous interferon and ribavirin therapy.

Boceprevir is a first-in-class oral hepatitis C virus (HCV) protease inhibitor, which works by binding to the virus and preventing it from multiplying. Boceprevir is the first direct acting antiviral drug against HCV to be approved.

Merck will begin shipping Victrelis to pharmacies within a week so that patients will have access to it as soon as possible.

“Getting Victrelis into US pharmacies within days of FDA approval is really a testament to the level of readiness, coordination, and execution excellence by the global Merck manufacturing organization,” Merck’s Pam Cheng, SVP, global supply chain and logistics, told Formulary.

The following points should be considered when initiating boceprevir for treatment of chronic hepatitis C infection:

• It must not be used as monotherapy and should only be used in combination with peginterferon alfa and ribavirin.
• Its efficacy has not been studied in patients who have previously failed therapy with a treatment regimen that includes boceprevir or other HCV NS3/4A protease inhibitors.
• Boceprevir in combination with peginterferon alfa and ribavirin has not been studied in patients documented to be historical null responders (less than a 2-log10 HCV-RNA decline by treatment week 12) during prior therapy with peginterferon alfa and ribavirin. The clinical studies included subjects who were poorly interferon responsive. Subjects with less than 0.5-log10 HCV-RNA decline in viral load at treatment week 4 with peginterferon alfa plus ribavirin alone are predicted to have a null response (less than 2-log10 viral load decline at treatment week 12) to peginterferon alfa and ribavirin therapy.
• Poorly interferon responsive patients who were treated with boceprevir in combination with peginterferon alfa and ribavirin have a lower likelihood of achieving a sustained virologic response (SVR), and a higher rate of detection of resistance-associated substitutions upon treatment failure, compared to patients with a greater response to peginterferon alfa and ribavirin.

Boceprevir must be administered in combination with peginterferon alfa and ribavirin. The dose of boceprevir is 800 mg (four 200-mg capsules) 3 times daily (every 7 to 9 hours) with food (a meal or light snack).

The safety and effectiveness of boceprevir was evaluated in 2 phase 3 clinical trials with 1,500 adult patients. In both trials, two-thirds of patients receiving boceprevir in combination with pegylated interferon and ribavirin experienced a significantly increased SVR (ie, HCV was no longer detected in the blood 24 weeks after stopping treatment), compared to pegylated interferon and ribavirin alone, the current standard of care.

When a patient sustains a virologic response after completing treatment, this suggests that HCV infection has been cured.

Sustained virologic response can result in decreased cirrhosis and complications of liver disease, decreased rates of liver cancer (hepatocelluar carcinoma), and decreased mortality.

“Victrelis is an important new advance for patients with hepatitis C,” said Edward Cox, MD, MPH, director, Office of Antimicrobial Products in FDA’s Center for Drug Evaluation and Research. “This new medication provides an effective treatment for a serious disease, and offers a greater chance of cure for some patients’ hepatitis C infection compared to currently available therapy.”

According to the Hepatitis C Association in Scotch Plains, N.J., hepatitis C affects 5 million people in the United States and more than 200 million people in the world. It is the leading cause of liver transplantation in the United States.