Results of Phase III Trial and Extension Study Data Presented by Cleveland Clinic Investigator at American Gastroenterological Association Meeting
Clinical results from familial adenomatous polyposis (FAP) patients treated with Aptosyn™(exisulind) for up to 18 months were presented today at the annual meeting of the American Gastroenterological Association (AGA) by Carol Burke, M.D. of the Cleveland Clinic Foundation. Results of a one year double-blinded, placebo-controlled Phase III trial and its six month open-label extension, sponsored by Cell Pathways, Inc. (Nasdaq: CLPA), demonstrate that Aptosyn™ induces a clinically significant reduction in the formation of precancerous colon polyps in patients with FAP after as little as six months of therapy. Moreover, patients who have continued on Aptosyn™ for more than one year continue to show further improvement over time.
In a separate release the company announced the presentation of preclinical research being presented at AGA showing that colonic tumor cells marked by hereditary defects different from the APC gene mutation that characterizes FAP also undergo apoptosis, or programmed cell death, when treated with Aptosyn. The company also reported laboratory findings that the cyclic GMP phosphodiesterase targeted by Aptosyn™ and other selective apoptotic antineoplastic drugs (SAANDs) is over-expressed in colonic neoplasias relative to normal colonic mucosal tissue. This observation may explain in part the selectivity of SAANDs for precancerous and cancerous cells and not for normal tissue.
Results of Phase III Trial and Extension Study
"Based on the clinical responses that we have observed to date, use of exisulind for the chemoprevention of colonic adenomas has the potential to significantly alter the management of patients with FAP," commented Dr. Burke, a principal investigator for the Phase III study and for the previous Phase II trial of Aptosyn™ in patients with FAP.
Since polyp formation rates in patients with FAP are variable, the original one-year Phase III study was prospectively designed to detect a statistical difference in polyp formation rates only in patients who historically formed between 10 and 40 new polyps per year. In 34 patients that fit the criteria, those treated with Aptosyn™ experienced a 53% reduction in the mean and median number of polyps formed versus placebo-treated patients. The patients tolerated the treatment with Aptosyn well.
Following the initial one-year study, patients in both the treatment and placebo arms that completed the Phase III trial have been offered Aptosyn™ therapy as part of a 12 month, open-label extension study. These patients receive 600 mg of Aptosyn™, total daily dose, and investigators count and remove all rectal polyps at six-month intervals. After six months of therapy in the extension trial, the crossover group (formerly placebo) showed a median polyp reduction of 50%. Patients who had been in the treatment arm showed an additional 50% reduction in polyp formation, or an overall 75% reduction after 18 months of therapy. The patients continue to tolerate treatment with Aptosyn™ well.
"Over 50% of my patients who participated in the original Phase II trial of Aptosyn™ have continued to take the drug for up to 57 months, and they no longer form clinically significant colon polyps," Dr. Burke commented.
"We are very encouraged by all of our results to date with Aptosyn™ as a potential new treatment for individuals with FAP, an indication for which it is currently under review by the Food and Drug Administration," commented Rifat Pamukcu, M.D., senior vice president of research and development and chief scientific officer of Cell Pathways. "In addition to these studies in adult FAP patients, we are currently conducting a study in children with FAP."
FAP is a relatively rare hereditary condition characterized by the development of hundreds to thousands of adenomatous polyps in the colon and rectum during adolescence and early adulthood. Experts consider adenomatous polyps to be precursor lesions to colorectal cancer. Left untreated, virtually all patients with FAP develop colorectal cancer by age 40-50. There are currently no drugs approved for the prevention of polyps in FAP, and these patients have very few disease management options.
Aptosyn™ (exisulind) is the first product candidate from a novel class of compounds under development by Cell Pathways, called selective apoptotic anti-neoplastic drugs (SAANDs). SAANDs inhibit a novel pattern of over-expressed cyclic GMP phosphodiesterases found in cancerous and precancerous cells. Inhibition of cGMP-PDE results in an increase of cGMP which activates PKG, a downstream regulator of apoptosis (programmed cell death). This activation allows the apoptotic pathway to proceed and selectively induce apoptosis in abnormally growing precancerous and cancerous cells. Because SAANDs do not induce apoptosis in normal cells, they do not produce the serious side effects normally associated with traditional chemotherapeutic agents. They also do not inhibit cyclooxygenase (COX I or COX II) and have not exhibited the gastric and renal toxicities reported to be associated with non-steroidal anti-inflammatory drugs (NSAIDs), including the COX II specific inhibitors. A New Drug Application for Aptosyn™ as a treatment for patients with FAP is currently under review by the Food and Drug Administration. The compound is also undergoing further clinical evaluation in a variety of additional precancer and cancer indications.
Cell Pathways, Inc., headquartered in Horsham, Pennsylvania, is a development stage pharmaceutical company focused on the research, development and commercialization of novel and unique medications to prevent and treat cancer. For additional information on Cell Pathways, Inc., visit the company's website at http://www.cellpathways.com.
Certain statements made herein, and oral statements made in respect hereof, constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements are those which express plan, anticipation, intent, contingency or future development and/or otherwise are not statements of historical fact. These statements are subject to risks and uncertainties, known and unknown, which could cause actual results and developments to differ materially from those expressed or implied in such statements. Such risks and uncertainties relate to, among other factors, the absence of approved products; history of operating losses; early stage of development; the costs, delays and uncertainties inherent in basic pharmaceutical research, drug development, clinical trials and the regulatory approval process, with respect to both the Company's current product candidates and its future product candidates, if any; dependence on development of Aptosyn™ (exisulind); the limitations on, or absence of, the predictive value of data obtained in laboratory tests, animal models and human clinical trials when planning additional steps in product development; the uncertainty of obtaining regulatory approval, including uncertainty of approval of the New Drug Application submitted for Aptosyn™ (exisulind) for familial adenomatous polyposis (a rare disease that puts those afflicted at high risk of developing colon cancer), whether in connection with the adequacy of the data generated in the clinical trials of Aptosyn™ (exisulind) or otherwise; the uncertainty of the effect of product approval, if achieved, on the market price of the Common Stock; the timing and scope of any approval which might be received for any compound for any indication in the future; acceptance by providers of healthcare reimbursement; the validity, scope and enforceability of patents; the actions of competitors; dependence upon third parties; product liability; and the need for further financing. These and other risks are detailed in the Company's reports filed from time to time under the Securities Act of 1933 and/or the Securities Exchange Act of 1934, including the sections entitled "Business," "Risk Factors," "Management's Discussion and Analysis of Financial Condition and Results of Operations" and "Other Events" in the Company's reports on Form 10-K for the year ended December 31, 1999, Form 10-Q for each of the first three quarters of 2000, Form 8-K for the month of August 1999, and Form S-3 filed in December 1999. You are encouraged to read these filings as they are made from time to time. They are available over the Internet from the SEC in its EDGAR database. Given the uncertainties affecting pharmaceutical companies in the development stage, current and prospective investors are cautioned not to place undue reliance on any such forward-looking statements, any of which may turn out to be wrong due to inaccurate assumptions, unknown risks, uncertainties or other factors. The Company undertakes no obligation to update or revise the statements made herein or the factors which may relate thereto.