Protease Inhibitors at Retroviruses Conference: Agouron's Results

The protease inhibitors now furthest along in human use or testing are saquinavir (Invirase(TM), by Hoffmann-La Roche -- the only protease inhibitor now approved), indinavir (Crixivan(R), by Merck), ritonavir (Norvir(TM), by Abbott), and nelfinavir (Viracept(TM), by Agouron -- the drug was formerly called AG1343). AIDS TREATMENT NEWS already examined the Abbott (issue #240) and Merck (issue #241) protease inhibitor results presented at the Retroviruses conference. (Little clinical information on saquinavir was presented there -- only one abstract, #155, on reduced viral sensitivity during treatment -- probably because Roche had already presented the available information during the FDA approval process.)

Agouron protease inhibitor is at an earlier stage of development than the other three; about 120 patients have taken nelfinavir in studies so far.

Agouron's latest clinical trial data on nelfinavir became available too late for regular submission to the Retroviruses conference, and was turned down for the Late Breaker session, which had room for less than a third of the abstracts submitted to it -- and established various selection rules under which Agouron's abstracts did not qualify. (An earlier study of nelfinavir was accepted at the Retroviruses conference.(1) Agouron provided some of the results of its recent trials to the press, and at a community meeting on January 31.

One recent small trial found an average maximum reduction of HIV viral load from nelfinavir alone of about 98% at the best doses, after four weeks. Everyone's CD4 count increased.

Also, Agouron reported that an ongoing trial of the combination of nelfinavir plus d4T has found a greater than 99% average reduction in viral load. In a majority of the volunteers using this combination, the viral load was reduced to below the limit of detection (about 500 copies per milliliter, with the assay which was used). In comparison, d4T alone reduced viral load by about 75% in this trial.

Agouron states that nelfinavir has shown an excellent safety profile, with only one of about 120 volunteers having stopped the drug due to adverse effects which possibly were drug related. The most common side effect is loose stools or diarrhea.

Larger trials of nelfinavir are now recruiting at more than 40 sites in over 30 U.S. cities. For more information, see the announcement in AIDS TREATMENT NEWS #240 (February 9, 1996), or call Agouron's information line, 800/501-2474.

References

1. Webber S, Shetty B, Wu E, and Zorbas M. In vitro and in vivo metabolism and cytochrome p450 induction studies with the HIV-1 protease inhibitor, VIRACEPT(TM) (AG1343). 3rd Conference on Retroviruses and Opportunistic Infections, January 28 - February 1, 1996, Washington DC [abstract #144].