FDA Panel Recommends Approval of New AIDS Drug

Date: November 15, 1995
Source: Food and Drug Administration (FDA)

FDA's Antiviral Drugs Advisory Committee on Nov. 7 recommended that the agency grant accelerated approval for saquinavir for treating advanced HIV infection in combination with nucleoside analogue drugs. Saquinavir is manufactured by Roche Pharmaceutical under the trade name Invirase. The following may be useful for answering questions.

Saquinavir is a protease inhibitor, a new class of compounds under study for treating HIV. Protease inhibitors interrupt a key step in the chemical sequence by which HIV replicates.

Controlled clinical trials on saquinavir enrolled 936 HIV- infected patients and tracked changes in CD4 cell counts (the number of these infection-fighting cells per ml in patients' blood) in subjects on three combinations of drugs: saquinavir with AZT, saquinavir with ddC, and saquinavir with both AZT and ddC. Saquinavir doses ranged from 75 to 600 mg three times a day. Analyses of CD4 counts were conducted over 16 weeks, and patients had the option of continuing treatment. Patients with CD4 counts ranging form 0 to 500 before treatment were enrolled in the trials. (Values greater than 800 are normal in healthy individuals.)

AZT and ddC are AIDS drugs of the nucleoside analogue class of compounds, which also inhibit HIV replication. AZT, or zidovudine, was approved in 1987 and is manufactured by Glaxo-Wellcome Inc. under the trade name Retrovir; ddC, or zalcitabine, received accelerated approval in 1992 and is manufactured by Roche under the trade name Hivid.

Over 16 weeks, CD4 cell counts increased an average of 30-40 cells above baseline levels among patients on saquinavir in combination with ddC or AZT plus ddC. The increases were larger in patients who were previously untreated with nucleoside analogues. Saquinavir doses of less than 600 mg three times a day did not produce discernable CD4 increases, even when used in combination with AZT.

Few adverse events were associated with saquinavir, and for most patients the drug was well tolerated.

Approval of the saquinavir marketing application would be granted as an accelerated approval, a regulatory mechanism under which the agency bases early marketing approval for a product on laboratory markers like CD4 cells counts, rather than on clinical endpoint such as delay in death or reduction of opportunistic infections.

Manufacturers of products granted accelerated approval must demonstrate within a reasonable period of time that the product provides true clinical benefit or the agency may withdraw the accelerated approval. Trials designed to demonstrate clinical benefits of saquinavir in combination with other nucleoside analogues are currently enrolled in adult and pediatric patients.

Information on ongoing clinical trials testing drugs for HIV infection may be obtained form the Public Health Service's AIDS Clinical Trial Information Service at 1-800-TRIALS-A.