Findings with citicoline show significant cognitive improvement among stroke patients.

LEXINGTON, Mass.--(BUSINESS WIRE)--Feb. 10, 1997-- Neuropsychological test findings among patients recovering from ischemic stroke who participated in a Phase 3 clinical trial completed in 1996 have demonstrated a significant improvement in the cognitive function of those patients who received citicoline, a drug under development by Interneuron Pharmaceuticals Inc. (NASDAQ:IPIC).

The findings, presented at the 22nd International Joint Conference on Stroke and Cerebral Circulation of the American Heart Association on Feb. 8, 1997, demonstrated that patients who were given 500 milligrams of citicoline within 24 hours following the onset of stroke symptoms and continuously for six weeks thereafter scored statistically significantly higher on a battery of tests measuring learning ability and memorization skills than did patients who received placebo. As previously reported, this group of patients also exhibited significantly improved neurologic function, as assessed by the Barthel Index at 12 weeks following stroke.

"This analysis marks the first time in stroke research that neuropsychological data have been gathered and analyzed in a systematic, detailed fashion among recovering patients to provide evidence of improved cognitive function in addition to improved neurologic function," said Creed Pettigrew, M.D., associate professor of neurology and director of the stroke program at the University of Kentucky. "The improvement in cognitive performance demonstrated among citicoline-treated patients suggests a potential for significantly broader efficacy and reduced time related to both the acute and longer term rehabilitation phases of stroke therapy.

"Combined with the well-tolerated nature of citicoline, the improvement in learning and memory functions underscores the practicality of this compound, which clinicians first administered within 24 hours following stroke and over a prolonged, six-week period of time in a Phase 3 trial," added Pettigrew. "I believe these findings are consistent with what we believe about how citicoline works in the brain, specifically its apparent role in increasing the production of acetylcholine and stabilizing and protecting brain cell membranes."

The neurocognitive tests administered in this trial included the Folstein Mini-Mental State Examination, the Hopkins Verbal Learning Test, Span Tests and Trailmaking Tests. In all of these tests, patients receiving 500 milligrams of citicoline daily achieved statistically significantly higher scores than did placebo patients at time points ranging from three to twelve weeks following stroke (p<.05).

These findings complement the previous analyses of Interneuron's first Phase 3 trial with citicoline, which demonstrated statistically and clinically significant improvement in a variety of neurologic functions among patients suffering from ischemic stroke who were treated with the optimal 500 milligram dose of citicoline as compared with patients receiving placebo. A second Phase 3 trial with citicoline for stroke is nearing the completion of patient enrollment. Pending the results of this trial, Interneuron plans to submit a New Drug Application (NDA) for citicoline for treatment of stroke with the FDA by then end of 1997.

Mechanism of Action

It is believed that citicoline has multiple mechanisms of action which limit stroke-induced brain damage:

-- limiting the extent of the infarct, or tissue damage caused by interrupted blood flow, by preventing the accumulation of toxic free fatty acids; -- promoting recovery of brain function by providing two components, cytidine and choline, required in the formation of nerve cell membranes; -- promoting the synthesis of acetylcholine, a neurotransmitter associated with cognitive function.

Interneuron Pharmaceuticals is a diversified biopharmaceutical company engaged in the development and commercialization of a portfolio of products and product candidates primarily for neurological and behavioral disorders. The company's lead products include: Redux for obesity, currently marketed by American Home Products and co-promoted by the company; citicoline for stroke, in Phase 3 clinical trials; and bucindolol for congestive heart failure, in Phase 3 clinical trials through Intercardia Inc., a majority-owned subsidiary. Interneuron's subsidiaries include: Intercardia Inc. focused on cardiovascular disease, Progenitor Inc. focused on gene discovery through developmental biology, Transcell Technologies Inc. focused on carbohydrate-based drug discovery and drug transport, and InterNutria Inc. focused on dietary supplement products.

Except for the descriptions of historical facts contained herein, this release contains forward-looking statements that involve risks and uncertainties as detailed from time to time in Interneuron's SEC filings under the Securities Act of 1933 and the Securities Exchange Act of 1934 under "Risk Factors" that could cause the company's actual results to differ significantly from those discussed in the forward looking statements including the uncertainties related to clinical trials and government regulation, dependence on third parties for clinical development, manufacturing and marketing, competition, product liability and other risks.

CONTACT: Interneuron Pharmaceuticals Inc.

Bobby W. Sandage Jr. or William B. Boni, 617/861-8444