SILVER SPRING, Md--The FDA's Antiviral Drugs Advisory Committee
took action on three anti-HIV agents at its most recent meeting,
recommending approval for Hoffmann-La Roche's protease inhibitor
saquinavir (Invirase) and Glaxo Wellcome's 3TC (Epivir) in combination
with other AIDS drugs, and favoring a new indication for Bristol-Myers
Squibb's stavudine (d4T, Zerit), to treat patients who no longer
respond to zidovudine (AZT, Retrovir).
If approved, the protease inhibitor Invirase would represent the
first new class of anti-HIV agents since the nucleoside analog
AZT 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 evidence
of effectiveness for the FDA to expedite approval. But the panel
voted against recommending use of the drug alone, saying there
was not enough evidence that Invirase alone is clinically effective
at 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 physicians
to attack HIV from two different routes. He said that six protease
inhibitors are currently being tested in the United States.
The advisory committee also recommended approval of 3TC in combination
with AZT. [The FDA has since approved this combination.] Preliminary
data suggest that the addition of 3TC delays development of resistance
to AZT and could even reverse such resistance, Glaxo Wellcome
said. Studies show that the combination raises CD4 counts while
reducing HIV viral burden for at least 6 months, company representatives
The panel noted that the combination appeared more effective when
given as initial HIV therapy, since greater effects were seen
in patients who had never been exposed to AZT than in those who
had 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 longer
respond to AZT. The drug is currently approved for use in adults
with advanced HIV infection who are intolerant of approved therapies
or who have had significant deterioration while receiving these