BETHESDA, Md--Whaijen Soo, MD, vice president for virology, Hoffmann-La
Roche, told the National Task Force on AIDS Drug Development that
the company's protease inhibitor, saquinavir (Invirase), is now
ready for phase III trials.
These randomized double-blind studies will involve 1,000 people
with advanced HIV infection who have discontinued or are unable
to take AZT (zidovudine, Retrovir) and have CD4 counts of between
50 and 300.
Protease inhibitors are antiretroviral agents that block the activity
of protease, an enzyme critical to the replication of HIV, Edward
Scolnick, MD, executive vice president for science and technology,
Merck & Co, said in his overview of this new class of drugs.
Phase I and II Studies
In vitro studies have shown that enzyme inhibition results in
production of noninfectious virus, he said. Phase I and phase
II studies done in Europe and the United States showed improvement
in the number of circulating CD4 lymphocytes and a reduction of
The benefit of protease inhibitors may be limited, however, because
of the ultimate development of drug resistance, a problem common
to all current commercially available antiviral compounds, Dr.
Invirase, alone and in combination with other antiviral drugs,
will be tested against a placebo, with clinical endpoints defined
by disease progression and survival, Dr. Soo told the Task Force.
He said that phase II studies showed that patients who received
Invirase in combination with other antiretroviral agents had the
greatest improvement in CD4 cell counts and reduction of viral