The proliferative skin disorder psoriasis is earning itsreputation as a heartbreaker, having fended off the clinicaladvances of yet another drug development company eager fora conquest.

Chemex Pharmaceuticals Inc. announced Wednesday that it hashalted clinical development of two of its candidate drugs fortreating psoriasis.

Although the compounds -- TCV-309 and Methotrezate -- diddemonstrate some beneficial effects (as compared to theplacebo or untreated controls) in separate Phase I trials,Chemex (NASDAQ:CHMX) decided that those effects were notsufficient to warrant further cost expenditures on developmentfor this indication. Chemex does intend to continue exploringthe efficacy of TCV-309 for treating atopic dermatitis, however.

Chemex of Fort Lee, N.J., is developing these drugs as part of itsjoint venture with Block Drug Co. Inc. of Jersey City, N.J.

At the end of January, Chemex initiated the Phase I trials on atopical formulation of TCV-309, which is a platelet activatingfactor (PAF) antagonist it licensed from Takeda Chemical Co., inpatients with mild to moderate psoriasis. Phase I trials on atopical formulation of Methotrezate -- a zinc salt ofmethotrexate invented by Chemex scientists -- in patients withsevere psoriasis, began in mid-February.

Although these two drugs for treating psoriasis didn't passmuster, Chemex has at least one more to try, CHX-108, forwhich it filed an investigational new drug (IND) application in1987.

CHX-108, an analog of Chemex's drug Masoprocol (a naturalextract from the creosote bush) has already been formulatedfor topical application and is essentially "ready to go,"commented Len Stigliano, Chemex's chief financial officer.

As well, the company "will continue to seek additional in-license drug candidates for the treatment of psoriasis," saidHerbert McDade Jr., Chemex's chief executive officer.

Chemex is the third company in recent months to abandonpsoriasis drug candidates due to marginal efficacy. Earlier thismonth, Agouron Pharmaceuticals Inc. (NASDAQ:AGPH)suspended early-phase clinical studies of its topical anti-psoriatic drug AG-85 because the drug failed to provideconvincing evidence of its efficacy on improving the lesionscharacteristic of this proliferative skin disease.

Agouron's compound has been rationally designed to inactivatethe enzyme thymidylate synthase, which is known to berequired for the proliferation of human cells.

And in May, Sphinx Pharmaceuticals Corp. (NASDAQ:SPHX)pulled its topical psoriasis treatment Kynac out of the clinic.Here again, the drug's effects on psoriatic lesions weren'tclinically meaningful. Sphinx has targeted its drug to inhibitprotein kinase Cs, key intracellular enzymes that act to regulateintracellular processes, including proliferation.

So far, only privately held BioCryst Pharmaceuticals Inc. seemsto be impressed enough with its psoriasis drug to be planningPhase II clinical trials.

The Birmingham, Ala., company ran a combined Phase I/II trialin April on its drug BCX-34, designed by structure-basedprinciples to inhibit the enzyme purine nucleosidephosphorylase (PNP), which in turn prevents T cellproliferation and the ensuing inflammatory response.

The course of treatment was just two weeks and only 12patients completed the protocol. But four of those had "strongresponses (both histopathologically and clinically) clearly dueto BCX cream," explained Harry Snyder, the executive directorof clinical development at BioCryst.

Although "most patients relapsed to some degree when thetreatment was stopped," Snyder said, "at least one patient hasbeen in total remission for several months now."

Snyder told BioWorld that BioCryst is "proposing to take thesedata and go into a series of Phase IIs" with longer treatmenttimes (of at least six weeks).

-- Jennifer Van Brunt Senior Editor

(c) 1997 American Health Consultants. All rights reserved.