Agouron Protease Inhibitor

Agouron Pharmaceuticals, Inc. of La Jolla, California, is developing a protease inhibitor called AG 1343, trade name Viracept(TM). Two small studies, each checking the tolerability and antiviral activity of different doses of the drug, in slightly different formulations, were presented at the late breaker session at ICAAC. The first study, with 22 volunteers, was conducted in the UK; the second study, in the U.S., with 30 volunteers, tested higher doses.

The main results (from the two studies together) were:

* The drug was well tolerated in all the doses tested. Some patients had small to moderate side effects, including diarrhea (which may have been due to the particular formulation of the capsules, which has been changed) and fatigue.

* Almost everyone had good responses either in viral load reductions, or in CD4 count increases; however, there was often no clear relationship between these two responses. CD8 cell counts were also found to increase.

* No clear dose-response relationship was found. But when blood levels were examined, those with higher levels of the drug had a more sustained response.

* Average viral load changes could be as much as 1.5 logs (about 30-fold) at maximum. But a number of patients had less than a one-log drop in viral load at 28 days; in the larger of the two studies, they were dropped from the study at that point.

* Both studies also noted improvement in clinical conditions, such as swollen lymph nodes, hairy leukoplakia, and folliculitis.