Providing a new alternative to AIDS patients who have developed resistance to multiple drugs, the Food and Drug Administration on Monday approved the first-ever pill that works by defending human immune cells instead of attacking the deadly virus.
The drug, which will be sold in the United States under the trade name Selzentry, prevents the AIDS virus from entering immune cells by clogging up a cell receptor known as CCR5. All previous drugs have targeted parts of the virus.
The last new class of drugs was approved by the FDA in 2003.
Drug-maker Pfizer Inc. plans to make Selzentry commercially available in September at a wholesale cost of $29 per day. Patients with limited treatment options have been able to apply for the pill through an expanded access program since the end of last year.
The FDA reviewed data on more than 600 patients that showed Selzentry, whose generic name is maraviroc, was effective when used in combination with other AIDS drugs. About 45% of the patients who took Selzentry as part of their regimen saw the amount of HIV in their blood drop to undetectable levels after 24 weeks. About 23% of those who added a placebo to their regimen saw a similar decline.
The agency delayed approval of the drug for about two months because of concerns about liver toxicity, said Dr. Debra B. Birnkrant, who directs the FDA's antiviral products division.
In June, the FDA received a report of a woman who had high levels of a liver enzyme that might have been due to Selzentry, she said.
A similar drug made by GlaxoSmithKline, called aplaviroc, also was linked to severe liver toxicity. Trials for that drug were halted in 2005.
The FDA re-reviewed the data and approved Pfizer's drug on the condition that the label include a black-box warning, the strongest possible advisory. Selzentry also will carry a warning about an increased risk of heart attack.
"I think the benefits of the drug clearly outweigh the risks," Birnkrant said.
To check on the drug's long-term effects, the agency will obtain data on patients for at least five years, she said.
Dr. Helmut Albrecht, who oversees the infectious diseases division at the University of South Carolina and was not involved in the drug's clinical trials, said he was "cautiously optimistic" about Selzentry.
Because the CCR5 site is known to be involved in tumor surveillance and other immune functions, researchers need to keep a close watch for new cases of cancer or other medical problems, said Albrecht, who was involved in an aplaviroc trial.
"It's so completely new that it is sort of difficult to see how well this is going to do over time," Albrecht said.
The FDA accelerated the approval process for Selzentry because it saw a pressing need for patients infected with drug-resistant forms of HIV, the virus that causes AIDS. These patients may use the drug if they have the kind of HIV that uses the CCR5 site to help it enter a cell.
About 50% to 60% of patients with resistant viruses are infected with ones that use the CCR5 site. HIV also can target other cell receptors to gain entry.
The only test for HIV receptor targets is made by Monogram Biosciences of South San Francisco. It was made available to the public Monday and will probably cost about $1,700, said Monogram Chief Financial Officer Alfred G. Merriweather.
A limited group of patients might be appropriate for Selzentry at the moment, said Dr. Malcolm D. John, who directs an HIV clinic at UC San Francisco and was not involved in the study. Patients who are controlling their virus with other regimens should probably stay on those drugs, he said.
He estimated that about 10 to 15% of his patients would be good candidates.
"I'm not going to be rushing to use it, but if I have the right patient, I'll use it," John said.
The approval of Selzentry comes amid a renaissance in the development of AIDS treatments. Promising results on another new class of drugs called integrase inhibitors were announced this year.