By Lisa Seachrist

Washington Editor

With a new drug application filed in another indication, Cell Pathways Inc. announced positive Phase II/III clinical trial results for its lead apoptosis-inducing drug, Aptosyn (exisulind), in prostate cancer patients.

The study of 96 men examined whether Aptosyn could slow the increase in prostate specific antigen (PSA) levels in the blood in prostate cancer patients who'd undergone radical prostatectomy and had begun to see their PSA levels rise. Patients with such an increase in PSA are likely to have a recurrence of the cancer and are at an increased risk of developing advanced disease.

The study showed the rise in average PSA levels for patients taking Aptosyn was significantly lower than those receiving placebo.

"These are very exciting findings," said Rifat Pamukcu, chief scientific office at the Horsham, Pa.-based company. "Particularly because the high-risk group saw the greatest inhibition in the rise of their PSA levels."

The company is in the process of conducting a subgroup analysis on trial data and designing a Phase III pivotal trial to be used for getting FDA approval for the drug in this indication.

"As far as I know, the FDA has never approved a drug based solely on PSA levels," Pamukcu said. "I think this study will be supportive data for any Phase III study we conduct."

Prostate cancer patients who've undergone radical prostatectomy and have increasing PSA levels are faced with the possibility of therapy that results in chemical castration. Such aggressive therapy leads to impotence, breast tissue growth and hot flashes. Pamukcu noted even delaying the need for chemical castration by a couple of years was a benefit to these patients.

Cell Pathways submitted an NDA for Aptosyn as means to prevent the formation of precancerous colorectal polyps in patients suffering from familial adenomatous polyposis (FAP) in August and amended that application in late October. (See BioWorld Today, Aug. 27, 1999, p. 1; and Oct. 28, 1999, p. 1.)

The company is also exploring its use as a treatment for breast and lung cancers, Barrett's esophagus and sporadic colonic polyps.

The drug is designed to trigger cell death by apoptosis in abnormal precancerous and cancerous cells without the toxicities of other therapeutic agents. A part of a class of compounds called selective apoptotic anti-neoplastic drugs (SAANDs), these compounds inhibit a cyclic GMP phosphodiesterase and selectively induce apoptosis in abnormally growing precancerous cells, but not in normal cells.

As a result of their selectivity, SAANDs don't produce the serious side effects associated with traditional chemotherapeutic agents such as myelosuppression.

Cell Pathways is collaborating with Rhone Poulenc Rorer to test Aptosyn in combination with Taxotere as a therapy for prostate, lung, breast and pancreatic cancers. The company has all rights to the drug and plans to use a contract sales organization to market the drug once it is approved.

An approval could come by mid-2000 because Aptosyn received orphan drug designation in 1994 for the treatment of FAP and fast-track status in 1998. Fast-track status usually results in an expedited review period; however, the company hasn't been informed by FDA that Aptosyn will receive such consideration.

Cell Pathways stock (NASDAQ:CLPA) closed Tuesday at $10.75, up $1 a share.