FDA Panel Recommends Approval of Merck’s Antiretroviral Raltegravir
An independent FDA panel of medical experts on Wednesday unanimously recommended accelerated approval of Merck's antiretroviral drug raltegravir, the Wall Street Journal reports (Corbett Dooren, Wall Street Journal, 9/6). Merck in June announced that FDA granted priority review status to raltegravir, an experimental integrase inhibitor. Raltegravir effectively decreases HIV viral loads after 24 weeks of use among HIV-positive people who have not responded to other treatments, according to a study published in the April 14 online edition of the journal Lancet. Raltegravir works by blocking an HIV enzyme called integrase. Integrase is one of the three enzymes necessary for HIV to replicate in the body, and integrase inhibitors stop HIV from inserting its genes into uninfected DNA. The other two enzymes necessary for viral replication, reverse transcriptase and protease, already are targeted by a variety of antiretrovirals.
FDA last week released a review of raltegravir ahead of the panel's meeting. According to the FDA review, which was posted on the agency's Web site, raltegravir is effective at treating HIV-positive people who have shown resistance to available treatments. Rash and increased levels of creatine in the blood were the most common side effects of the drug, according to the review. Other potential side effects include liver injuries and cancer. In clinical trials, a higher number of cancers were found among people taking raltegravir than among those taking a placebo, but the difference could be because of a lower rate of cancer among people in the placebo group, FDA said.
The panel was asked whether raltegravir should be used only by people enrolled in clinical trials or by people "with few or no remaining treatment options." In addition, FDA asked the panel if Merck should be required to conduct postmarketing studies on the drug. The agency is expected to make a final decision about raltegravir in mid-October (Kaiser Daily HIV/AIDS Report, 9/4).
According to the Journal, the panel did not recommend which drugs should be used in combination with raltegravir or whether it should replace a drug in a standard three-drug regimen to treat HIV (Wall Street Journal, 9/6). Some panel members expressed concern over the increased number of cancers among people taking raltegravir in clinical trials; however, representatives from Merck and FDA noted that the cancer rate was comparable to that found among HIV-positive people with a highly drug-resistant strain of the virus (Chong, Los Angeles Times, 9/6). Some panel members recommended that FDA limit the drug's labeling for people who have developed resistance to multiple treatment regimens (Dixon, Reuters, 9/5). Several panel members also recommended that the agency require Merck to conduct follow-up studies among people taking the drug for up to five years (Los Angeles Times, 9/5).
Merck said that if the drug is approved, it will be used in combination with standard oral antiretrovirals by HIV-positive people who have developed resistance to their current treatments. Raltegravir will be sold under the brand name Isentress (Kaiser Daily HIV/AIDS Report, 9/4).