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(Drug information on 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 viral load.
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. Scolnick said.
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 load.