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.