By Karen Pihl-Carey

Cell Pathways Inc. filed a new drug application for Aptosyn (exisulind) to treat adenomatous polyposis coli (APC) and could have the polyp-reducing drug on the market in April.

"Obviously, for an emerging pharmaceutical or biotechnology company, it is a major milestone to achieve," CEO Robert Towarnicki said. "I think it brings us much closer to the hope and the dream of commercialization."

That dream may come by April, if the FDA approves the drug, which was designated a fast-track product in 1998, as well as an orphan drug in 1994. As of Wednesday, when the new drug application was filed, the FDA had 180 days to approve it, but that will be extended another 90 days when Cell Pathways submits by December supplemental data from extension studies.

The supplemental data will consist of results from 12 Phase I/II patients who have been on the drug for three years, as well as data from Phase III placebo patients crossed over to the drug group and patients still in the drug group. The company also has a 26-patient blinded study to be completed by the end of September, Towarnicki told BioWorld Today.

"Assuming that we get approval, we would expect a launch very shortly thereafter," Towarnicki said. "We intend to go directly into the market ourselves. We are currently looking at different ways of fielding a sales force."

The company found in February that Aptosyn, previously called Prevatac, did not achieve statistical significance in a Phase III study. But good news came later after further analysis when Cell Pathways found that the patients studied in Phase III generated several more polyps than the 10 to 40 expected, making it difficult for the small study to demonstrate significance. (See BioWorld Today, Feb. 3, 1999, p. 1; and June 16, 1999, p. 1.)

Through analysis of the 34 patients who developed the number of polyps expected, Cell Pathways found that the 15 exisulind patients showed a reduction of more than 50 percent in new polyp formation, compared to placebo patients.

APC is a rare disease that puts people at a high risk for colon cancer. A substantial portion of the large intestine is removed from most APC patients by the time they turn 20. Aptosyn, the result of a five-year clinical effort, is designed to trigger cell death by apoptosis in abnormal precancerous and cancerous cells without the toxicities of conventional therapeutic agents. If approved, the drug could provide the first non-surgical treatment option to people with APC.

"It's estimated in the U.S. that there's anywhere between 15,000 and 25,000 patients" with APC, Towarnicki said. "It's truly an orphan market in this initial indication. Of course, hopefully, we'll see an expansion of the market" as approvals are gained in other indications.

The company is in various stages of studying Aptosyn for other indications. It is in the middle of two studies in prostate cancer indications. One of the studies, a double-blind, placebo-controlled trial, should be completed in late September with results reported in the fourth quarter. Aptosyn also is being tested in a Phase II/III trial for recurrent breast cancer. The trial focuses on women who went into remission twice following two bouts of breast cancer.

"Breast cancer in 70 percent of that population will occur yet again within 18 months," Towarnicki said, "and there's no treatment for them." Cell Pathways has recruited 35 women for the study and is looking for 270 more.

An open-label study in late-stage lung cancer is under way, as is a Phase II trial in Barrett's esophagus syndrome. Cell Pathways also is studying in a Phase II/III trial whether Aptosyn can reduce sporadic colonic polyps. That trial is blinded and consists of three arms - placebo, low dose and high dose. It should be completed in March, Towarnicki said.

Aside from Aptosyn, the company completed its Phase Ia trial of CP-461, a compound with higher apoptotic potency targeted for cancer indications.

"It appears on single-dose trials that we are achieving very significant plasma levels that assure we are exposing the cancers to the drug," Towarnicki said.

The company's stock (NASDAQ:CLPA) gained 50 cents Thursday to close at $12.50.