By Karen Pihl-Carey

Cell Pathways plans to submit new data to support its recent new drug application for Aptosyn (exisulind) to treat patients with familial adenomatous polyposis (FAP).

The data from the three additional trials showed the drug prevents the formation of precancerous colorectal adenomatous polyps in patients with FAP, or more specifically, in patients with adenomatous polyposis coli (APC).

"What we saw in these results just reconfirmed what we saw originally in our Phase I/II and Phase II/III studies," said Robert Towarnicki, president and CEO of the Horsham, Pa.-based company.

The company submitted an NDA for Aptosyn for FAP in August. (See BioWorld Today, Aug. 27, 1999, p. 1.)

In one of the extended studies, 25 of 48 patients who had received placebo for one year in a blinded Phase II/III trial began receiving Aptosyn for six months on an open-label basis. After the six months, the patients experienced a 50 percent reduction in their polyp formation rate across the colorectum. The 23 patients who received Aptosyn in the one-year study continued taking it for another six months. They demonstrated a further decline in their polyp formation rate, another 50 percent below the already reduced rate. Cell Pathways will continue to monitor all 48 patients as they continue to take Aptosyn another six months.

A second extended study involved 11 patients who originally participated in a six-month open-label Phase I/II trial. The patients continued with the therapy and have been receiving Aptosyn for 36 to 50 months. After two years, they experienced statistically significant reductions in polyp formation rates during two years of therapy, the company said. In the third year, their polyp formation rates remained at the reduced levels.

A third study, which was double-blind and placebo-controlled, involved 26 patients. It showed the same results - a reduction in new polyp formation in FAP patients when compared to placebo.

"We feel they're strongly confirmatory of the results we've seen previous to this and confirmatory of the efficacy of the drug," Towarnicki told BioWorld Today.

Aptsoyn is designed to trigger cell death by apoptosis in abnormal precancerous and cancerous cells without the toxicities of other therapeutic agents. It comes from a new class of compounds called selective apoptotic anti-neoplastic drugs (SAANDs). Aside from its NDA to treat FAP, Aptosyn is in clinical trials for prostate, breast and lung cancers, Barrett's esophagus and sporadic colonic polyps.

FAP is a rare hereditary disease in which hundreds to thousands of adenomatous polyps develop in the colon and rectum during adolescence and early adulthood, putting a person at a high risk for colon cancer.

"It's estimated in the U.S. that there are somewhere between 15,000 and 25,000 patients who suffer from this disease," Towarnicki said. "And there are similar numbers in Europe and in Asia. So that's one of the reasons we have orphan drug status for this indication."

The company received orphan drug status for Aptosyn in 1994 and fast-track status in 1998.

The company hopes for FDA approval of Aptosyn next spring. Cell Pathways announced two weeks ago it raised about $14 million through a private placement of 1.555 million shares of stock at $9 per share. The money raised will go toward clinical programs of Aptosyn and CP461 for cancer indications, as well as for marketing of Aptosyn. (See BioWorld Today, Oct. 13, 1999, p. 1.)