Could AIDS Drug Have Made a Difference?
Dec. 21, 1999 (Atlanta) -- An experimental anti-HIV drug was moderately effective and too toxic for at least half the people who took it, but was it withdrawn from further development too soon? A study of the drug, published in The Journal of the American Medical Association (JAMA), shows that the drug might have been able to help HIV-infected people for whom other treatments no longer worked.
Gilead Sciences Inc. discontinued U.S. development of the drug, adefovir dipivoxil, after failing to win the approval of an FDA advisory committee. It was the first time such a committee ever rejected an AIDS therapy. The drug is still being considered as a possible treatment for hepatitis B.
The published study findings show that adefovir was effective when added to existing treatments in patients whose HIV levels remained high. But 60% of patients developed signs of kidney toxicity after taking the drug for 24 to 48 weeks.
"This particular drug shows potent antiretroviral activity in patients with HIV when given in combination with other agents," study co-author Stephen W. Lagakos, PhD, tells WebMD. "It can add to the existing antiviral effect of other drugs, that's very good. On the other hand, this drug has a side effect that occurs in a high percentage of patients that is not good."
Based on these results, adefovir would not be an appropriate first-line therapy. However, there currently are very few salvage options for patients failing other agents. Lagakos believes that the trial results show adefovir could be useful in such a setting.
"Patients who have failed on other antiretroviral drugs are in a desperate situation," says Lagakos, a researcher at the Harvard School of Public Health. "At some point people need help, and this drug has been shown to be effective in patients who have failed other drugs. There is a real risk of side effects, but they are reversible if you are aware of them."
There is evidence from other, smaller studies that a 60 mg dose of adefovir might be less toxic and have a lower incidence of side effects than the 120 mg dose used in the study. But this evidence, along with Lagakos' study, was too thin for an FDA advisory committee, which last month voted 13 to 1 against recommending adefovir for accelerated approval. Earlier this month, Gilead withdrew adefovir from further U.S. development (an application for European approval is still pending).