Safety worries mar hope for novel HIV drug

updated 12:50 p.m. ET April 20, 2007

WASHINGTON - Health officials repeated safety concerns about an experimental group of HIV drugs Friday, days before government advisers will recommend whether the first drug from the class merits approval.

Pfizer Inc. seeks Food and Drug Administration approval for maraviroc, potentially the first in a novel group of drugs to fight HIV, the virus that causes AIDS. Pfizer proposes marketing maraviroc as Celsentri.

Pfizer believes there is a clear unmet need for new drugs to fight HIV in patients for whom other, older drugs no longer work. Celsentri is unlike any other HIV medicines now on the market in that it targets the cells of patients and not the virus itself.

The FDA has scheduled a Tuesday meeting of outside experts to discuss Pfizer’s application for approval. The FDA has asked the experts whether Celsentri, if approved, would require special labeling or if further study of the drug’s safety is needed before it can be sold. FDA also asked whether the drug should be studied further in women and blacks.

The FDA and Pfizer both said that studies showed adding Celsentri to a traditional HIV treatment regimen was more effective in dropping the virus below detectable levels in patients.

But the FDA continues to be concerned about potential safety issues with the entire class of drugs, called CCR5 receptor antagonists. Those issues include the possibility the drugs could increase the likelihood of infection, lymphoma or liver damage in HIV patients. They’ve also been linked to heart rhythm changes in laboratory animals.

Shift in type of HIV
Most worrisome is that the drugs could accelerate a shift from one variant of HIV to a second, which is most often seen in the sickest AIDS patients. Patients on Celsentri likely would have to be tested regularly to monitor whether the drug is driving such a shift.

Still, FDA reviewers noted no increase in lymphomas or infections among patients given Celsentri, but said there was a modest increase in liver problems.
Pfizer, in its own analyses of studies of the drug, said the studies showed no significant effect on the heart, and no increased incidence of liver problems, cancer or infection compared with treatment with other HIV drugs.

Previously, those sorts of safety concerns set back GlaxoSmithKline and Schering-Plough Corp. in their development of similar CCR5 receptor antagonists.

The drugs block a secondary but crucial doorway typically used by the human immunodeficiency virus to enter white blood cells. A body’s white blood cells play an important role in the immune system.

Researchers have known for more than a decade that people who lack a working version of that doorway, called a receptor, are, at best, highly resistant to infection by HIV and, at worst, slow to develop AIDS once infected.

Since 1987, the FDA has approved 29 drugs, including combination medicines, in four different classes to fight HIV. CCR5 receptor antagonists would represent a new, fifth class.

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