FDA Approves Boceprevir for HCV

Emma Hitt, PhD

May 16, 2011

May 16, 2011 (UPDATED May 28, 2011) — The US Food and Drug Administration (FDA) has approved boceprevir (Victrelis, Merck) for hepatitis C virus (HCV) infection, making it the first new drug for HCV in 20 years.

Boceprevir is approved for the treatment of chronic HCV genotype 1 infection, in combination with peginterferon alfa and ribavirin, in patients aged 18 years and older with compensated liver disease, including cirrhosis, who are previously untreated or in whom previous interferon and ribavirin therapy have failed.

Boceprevir interferes with the ability of the HCV to replicate by inhibiting a key viral enzyme (NS3/4A serine protease). The drug is available as 200-mg capsules, with a recommended dosage of 800 mg administered orally 3 times daily (every 7 - 9 hours) with a meal or with a light snack.

Approval Expected, Study Results

The FDA's approval last week was expected, given the Antiviral Drugs Advisory Committee's 18 to 0 vote on April 27 that boceprevir should receive FDA approval for this indication.

The approval was based on trial data from the results of a couple phase 3 randomized trials, conducted in approximately 1500 previously treated and untreated patients, reported in the March 31 issue of the New England Journal of Medicine.

These studies found that compared with the control group, receiving the standard of care (ribavirin plus pegylated interferon), the patients who also received boceprevir had a significantly higher rate of sustained virologic response. The new treatment effectively doubled the sustained virologic response rate, from approximately 20% to 40% with the standard of care to, in some cases, more than 60% with added boceprevir.

"When a person sustains a virologic response after completing treatment, this suggests that HCV infection has been cured," the FDA release notes.

Serious adverse events were reported in 11% of patients receiving boceprevir in combination with peginterferon and ribavirin compared with 8% of patients receiving peginterferon and ribavirin alone, out of more than 2000 patients in phase 2 and 3 studies of boceprevir.

The most commonly reported adverse reactions (>35%) were fatigue, anemia, nausea, headache, and dysgeusia. The most common reason for dose reduction in the trials was anemia.

Contraindications, Precautions

Because boceprevir must be given as combination therapy with peginterferon alfa and ribavirin, all contraindications to peginterferon alfa and ribavirin also apply to boceprevir. For example, boceprevir is contraindicated in pregnant women and in men whose female partners are pregnant, because ribavirin may cause birth defects and fetal death. Women must have a negative pregnancy test result before starting combination therapy, use at least 2 forms of contraception, and have monthly pregnancy tests during treatment.

Boceprevir is a strong inhibitor of cytochrome 3A4/5 (CYP3A4/5) and is partly metabolized by CYP3A4/5. Therefore, it is contraindicated in patients taking drugs that are highly dependent on CYP3A4/5 for clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening events. Boceprevir is also contraindicated in patients taking potent CYP3A4/5 inducers, because significantly reduced boceprevir plasma concentrations may result in reduced efficacy.

Compared with peginterferon alfa and ribavirin alone, the addition of boceprevir to combination therapy is associated with further reduction in hemoglobin concentrations and worsening of neutropenia.

The safety and efficacy of boceprevir have not been studied in pediatric patients, in patients with decompensated cirrhosis, in patients with an organ transplant, in patients coinfected with HCV and HIV, or in patients coinfected with HCV and hepatitis B virus (HBV).

Available to Pharmacies Soon

"[Boceprevir] is an important new advance for patients with hepatitis C," noted 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."

In a company press release, Merck notes that it will begin shipping boceprevir to pharmacies within a week. In addition, the company is making available resources that include "coupons to help eligible patients with their medication cost, reimbursement support to help patients understand their insurance coverage for boceprevir, and 24/7 nurse phone support."

Boceprevir interferes with the ability of the HCV to replicate by inhibiting a key viral enzyme (NS3/4A serine protease). The approval of telaprevir (Vertex), another member of the same class of agents, was also supported by the Antiviral Drugs Advisory Committee, and FDA approval of this drug is also expected.

Laurie Barclay, MD, contributed to this news article.


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