Panel Recommends FDA Approval of First Protease Inhibitor

SILVER SPRING, Md--The FDA's Antiviral Drugs Advisory Committeetook action on three anti-HIV agents at its most recent meeting,recommending approval for Hoffmann-La Roche's protease inhibitorsaquinavir (Invirase) and Glaxo Wellcome's 3TC (Epivir) in combinationwith other AIDS drugs, and favoring a new indication for Bristol-MyersSquibb's stavudine (d4T, Zerit), to treat patients who no longerrespond to zidovudine (AZT, Retrovir).

If approved, the protease inhibitor Invirase would represent thefirst new class of anti-HIV agents since the nucleoside analogAZT became available in 1987. Other available anti-HIV agents,didanosine (ddI, Videx), zalcitabine (ddC, Hivid), and stavudine,are all nucleoside analogs.

In a 6 to 1 vote, the panel stated that there was sufficient evidenceof effectiveness for the FDA to expedite approval. But the panelvoted against recommending use of the drug alone, saying therewas not enough evidence that Invirase alone is clinically effectiveat the low doses tested in the preliminary studies.

FDA Commissioner David Kessler expressed enthusiasm over the recommendation,saying that the availability of Invirase would allow physiciansto attack HIV from two different routes. He said that six proteaseinhibitors are currently being tested in the United States.

The advisory committee also recommended approval of 3TC in combinationwith AZT. [The FDA has since approved this combination.] Preliminarydata suggest that the addition of 3TC delays development of resistanceto AZT and could even reverse such resistance, Glaxo Wellcomesaid. Studies show that the combination raises CD4 counts whilereducing HIV viral burden for at least 6 months, company representativessaid.

The panel noted that the combination appeared more effective whengiven as initial HIV therapy, since greater effects were seenin patients who had never been exposed to AZT than in those whohad previously received AZT monotherapy.

The panel also recommended 4 to 3 that the indication for stavudine(d4T) be extended to include treatment of patients who no longerrespond to AZT. The drug is currently approved for use in adultswith advanced HIV infection who are intolerant of approved therapiesor who have had significant deterioration while receiving thesetherapies.