By Jim Shrine
Cell Pathways Inc., after completing further analysis from what appeared to be a failed Phase III trial of exisulind in adenomatous polyposis coli (APC), said it plans to submit a new drug application (NDA) this summer.
The Horsham, Pa., company in early February released initial data showing exisulind did not produce a statistically significant reduction in new polyp formation in a trial of 65 patients with the inherited disease. But the patients had more variability in polyp formation than the 10 to 40 that were expected to develop over a year, hurting the chance for the relatively small study to demonstrate significance.
Cell Pathways then analyzed only the 34 patients who developed those number of polyps, and found, in that group, that the 15 exisulind patients did show a reduction of more than 50 percent in new polyp formation compared to placebo patients.
"We think this is very positive," said Robert Towarnicki, president and CEO of Cell Pathways. "We're very happy we found some of the issues [that skewed the initial analysis], and we believe we've demonstrated in a population of people an efficacious drug response. We're also happy that we have the other patient populations to support us as we go forward in the application process."
APC, which afflicts an estimated 10,000 to 25,000 people in the U.S., is characterized by the development of hundreds to thousands of adenomatous polyps in the colon, a precursor to colon cancer. The drug was put on the FDA's fast track, meaning the agency has six months to issue a decision upon submission of the NDA.
But Cell Pathways plans to submit additional data in the fourth quarter from three studies, as requested by the FDA, pushing back that time line by three months.
The company's stock (NASDAQ:CLPA) took a 66 percent hit in February, when the Phase III trial results were first disclosed, falling to $9 per share. But there was no resurgence in the stock upon news that the trial actually will support a filing, as it fell $3.062 Tuesday to close at $10.937.
Towarnicki said after meeting with the FDA "we concluded it was in our best interest to go through with the filing. We feel we have found the issues around the trial and have adjusted for them, and are presenting to the FDA some valid data, albeit not sufficient in itself to gain approval."
Supplemental data expected to be filed later in the year will come from extension studies of the original Phase I/II trial, involving 12 patients who have been on the drug more than three years in an open-label study; more data from the Phase III trial, including from placebo patients later crossed over to the drug group; and data from a study of about 25 patients who became available after recruitment in the Phase III trial was closed, but nevertheless were treated in the same manner.
Exisulind, or Prevatac, is a metabolite of a non-steroidal anti-inflammatory agent called sulindac. The apoptotic compound targets GMP phosphodiesterase, without inhibiting COX pathways.
In May, Cell Pathways released interim Phase II/III trial results showing exisulind produced statistically significant reductions in prostate specific antigen levels in a patients following radical prostatectomy. That one-year study is expected to be completed late in the third quarter. (See BioWorld Today, May 7, 1999, p. 1.)
Earlier this month the company initiated two open-label studies of exisulind in prostate cancer indications. The drug also is being studied in a slowly enrolling Phase II/III trial for recurrent breast cancer, two early studies in lung cancer, and a Phase II trial in Barrett's esophagus syndrome.