Agouron Pharmaceuticals Inc. has suspended early-phaseclinical studies of its topical anti-psoriatic agent due to lack ofefficacy, the San Diego company announced Wednesday.

Agouron had anticipated that the drug, AG-85, might halt theabnormal proliferation of skin cells characteristic of psoriasisbecause it has been rationally designed to inactivate theenzyme thymidylate synthase (TS), which is known to berequired for the proliferation of human cells.

But in the clinical study, conducted at the Skin ResearchFoundation of California in Santa Monica and the University ofCalifornia, Irvine, the compound failed to provide convincingevidence of its efficacy.

The psoriatic lesions on 22 patients were treated for six weekswith a 1.25 percent cream formulation of AG-85; the creamvehicle served as a control. A preliminary analysis of theresults demonstrated that the extent of improvement of thelesions treated with AG-85 was not significantly superior tothat of lesions treated by the cream vehicle alone.

"It's unclear whether the lack of anti-psoriatic effect is a resultof a delivery problem, a (drug) stability problem or whetherthymidylate synthase is a viable molecular target for psoriasis,"said Donna Nichols, Agouron's (NASDAQ:AGPH) director ofcorporate communications.

"We're not prepared to proceed with the development of TSinhibitors for psoriasis unless we resolve this last issue."However, "if another company is prepared to invest inexploring these issues Agouron would be receptive to alicensing agreement," Nichols told BioWorld.

In fact, another company is already exploring efficacy issues onanother topical anti-psoriasis drug. Sphinx PharmaceuticalsCorp. in May announced that it had halted clinical trials of itstopical ointment Kynac, which is a protein kinase C (PKC)inhibitor, because the drug's effects on psoriatic lesions weren'tclinically meaningful.

Sphinx (NASDAQ:SPHX) of Durham, N.C., is questioning whetherto reformulate the drug or go with a more potent PKC inhibitor,whose mode of action is to interfere with the key intracellularenzymes that act to regulate cellular processes (such asproliferation).

Meanwhile, Agouron is continuing its clinical developmentprograms on two other unrelated, structurally distinct TSinhibitors in its portfolio. Both AG-331 and AG-337 arecurrently in Phase I trials for treating solid tumors. Both arecurrently being infused into patients, although there's someindication from preclinical tests that AG-337 has oralbioavailability, Nichols explained. Agouron's stock was down75 a share Wednesday, closing at $9.

"We do not believe that disappointing results from clinicalstudies of AG-85 in psoriasis raise any new questionsconcerning the usefulness of TS inhibitors in cancer," saidRobert Jackson, vice president of research and development atAgouron. "While it is too early in the clinical evaluation of AG-331 and AG-337 to draw any conclusions regarding theirefficacy, we know from the performance of other compoundsthat pure TS inhibitors are capable of producing anti-tumoreffects in humans."

-- Jennifer Van Brunt Senior Editor

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