New data from three additional trial studies confirm that long-term use of exisulind (Aptosyn) prevents the formation of precancerous colorectal adenomatous polyps in patients with familial adenomatous polyposis (FAP). These clinically significant findings, which were recently announced by Cell Pathways, support and extend the results of previous studies in patients with FAP.
These findings are quite consistent with the results from our previous pivotal phase I/II and phase II/III trials. We are submitting these additional clinical data to the US Food and Drug Administration (FDA) in support of our new drug application for Aptosyn that was submitted on August 25, 1999, said Robert J. Towarnicki, president and chief executive officer of Cell Pathways.
Exisulind belongs to a new class of compounds called selective apoptotic antineoplastic drugs (SAANDs). These compounds inhibit a cyclic guanosine monophosphate (GMP) phosphodiesterase and selectively induce apoptosis in abnormally growing precancerous and cancerous cells but not in normal cells.
First Two Trials Show Significant Reductions in Polyp Formation
The first of three trials involved 48 of the patients who completed the phase II/III study of exisulind in early 1999. Of the 48 patients, 25 had received placebo for 1 year as part of the blinded phase II/III trial, and then received exisulind on an open-label basis for an additional 6 months. After 6 months, these 25 patients experienced a clinically and statistically significant, 50% reduction in polyp formation rate across the entire colorectum.
The remaining 23 patients received exisulind for 1 year during the earlier study and continued taking the drug for an additional 6 months. At the end of this period, these patients demonstrated further declines in their polyp formation rate, to 50% below the already reduced rate that they had experienced across the entire colorectum during the first year. These additional declines were also clinically and statistically significant. Cell Pathways plans to continue monitoring the 48 patients as they continue the drug for at least another 6 months.
The second trial was an extension study of 11 patients who participated in a 6-month open-label phase I/II dose-ranging safety and efficacy trial of exisulind. These patients have been receiving exisulind for 36 to 50 months and are continuing therapy. During the first 2 years, exisulind, taken at optimal doses, achieved statistically significant reductions in polyp formation rates. These rates remained at the same reduced levels during the patients third year of therapy.
Double-Blind Safety Study
The third study was a double-blind, placebo-controlled safety study of 26 patients. The trend in the data, including all patients, supports the previously seen results that exisulind reduces new polyp formation in FAP patients when compared to placebo.
As we observed in earlier studies, the FAP patients in these studies experienced a significant reduction in precancerous colon polyp formation while maintaining this effect over long periods of time. The durability of the clinical effect is one of the most important characteristics of any drug intended to be used for the lifelong treatment and prevention of precancerous lesions, commented Rifat Pamukcu, MD, chief scientific officer and senior vice president of research and development at Cell Pathways. In addition, Aptosyn was generally well tolerated by patients during the course of all three studies.