Important note: Information in this article was accurate in 2007. The state of the art may have changed since the publication date.
Los Angeles Times - September 6, 2007
Jia-Rui Chong, Los Angeles Times Staff Writer, jia-rui.chong@latimes.com
Isentress, developed by Merck & Co., is the first in a class known as integrase inhibitors, which prevent HIV from merging into the DNA of human cells.
The panel's recommendation follows the approval last month of Pfizer Inc.'s Selzentry. The drug is a CCR5 inhibitor, the first new class approved since 2003.
"I think we have kind of come to another milestone in the treatment of HIV," said Dr. Richard Haubrich, a professor of medicine at UC San Diego, referring to the relative bounty of new drugs available to treat AIDS.
Jeff Bailey, director of client services for AIDS Project Los Angeles, added: "Anytime a new option comes up for persons living with HIV that demonstrates efficacy, is relatively easy to tolerate with few side effects, that's definitely cause for excitement."
Some members of the Food and Drug Administration advisory panel expressed concern over data showing a higher number of cancers and abnormal tissue growths in patients taking Isentress.
But Merck representatives and FDA staffers said the rate of malignancies was comparable with that found in patients with a highly drug-resistant virus.
"Overall, based on the data we've seen today, the risk-to-benefit ratio seems fairly favorable," said Dr. Marshall Glesby, an advisory panel member and co-director of the Cornell University HIV Clinical Trials Unit.
Full approval of Isentress, whose generic name is raltegravir, is expected within the next few months. The FDA is not required to follow the recommendation of its advisory panel but usually does.
The malignancy issue focused on data from three clinical trials involving about 900 patients with multi-drug resistance.
About 600 subjects received Isentress and a cocktail of other AIDS drugs; 282 patients received a standard cocktail with a placebo.
In the Isentress group, 13 patients developed malignancies, such as squamous cell carcinoma or lymphoma, during the trial, which lasted 16 to 24 weeks. None of the patients taking a standard drug regimen plus placebo had any malignancies.
An FDA analysis of the studies said the difference between the two groups appeared to be a result of chance. Isentress didn't necessarily cause more malignancies -- rather, the placebo group had an unusually low number, the analysis found.
Dr. Robert Yarchoan, an advisory panel member and chief of the HIV and AIDS Malignancy Branch at the National Cancer Institute, said the difference in numbers appeared to be "a sort of a random blip."
Several of the 11 members of the advisory panel, which met in Silver Spring, Md., recommended that Merck conduct five years of follow-up studies to confirm the drug's safety.
The effectiveness of the drug was demonstrated in two studies involving about 700 patients who had developed resistance to at least three existing classes of AIDS drugs. A cocktail that included Isentress suppressed the amount of HIV in the blood to undetectable levels in about 62% of patients. A placebo regimen suppressed the virus in about 34%, according to the studies.
The number of patients resistant to three classes of drugs has risen from about 16% in 2000 to 26% in 2006 in some urban clinics, said Haubrich, who has consulted for Merck and other pharmaceutical companies.
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