By Frances Bishopp

Interneuron Pharmaceuticals Inc. reports results from Takeda Chemical Industries Ltd.'s Phase III clinical trial for the stroke drug citicoline support Interneuron's Phase III findings. Assuming its second Phase III trial is positive, the company will include the Takeda study in its new drug application to the FDA planned for the end of the year.

Takeda, of Osaka, Japan, already markets citicoline for stroke and head trauma in Japan and other countries. The company conducted the study among 267 ischemic stroke patients to evaluate functional improvement up to four months and mortality rates within one year after stroke.

Previously unpublished and only recently acquired by Interneuron, the Takeda study results demonstrated improved functional recovery and significant reduction in mortality: 17 citicoline deaths vs. 35 placebo deaths 450 days after stroke.

In early 1996, Interneuron completed a 259-patient Phase III trial for citicoline for improved neurologic function as assessed by the Barthel Index (a standard of measuring neurologic function that uses a 100-point rating scale) and other neurological measurements. The trial results demonstrated significant improvement in the recovery of ischemic stroke patients when compared to placebo.

A second-round analysis of the Phase III focused on cognitive function, as assessed by a battery of tests measuring learning and memory functions, showed citicoline-treated patients experienced an improvement in learning and memorization.

Interneuron, of Lexington, Mass., currently is conducting a second 400-patient Phase III trial of citicoline for improved neurologic function in the U.S. The first Phase III trial measured patients who took three different doses of citicoline (500 mg, 1,000 mg and 2,000 mg per day orally for six weeks) against placebo.

Among those who received 500 mg of citicoline daily, 53 percent achieved a Barthel Index score of 95 or more at 12 weeks, compared with 33 percent of placebo patients. Patients in the 500 mg group achieved complete or near-complete recovery two weeks faster than those taking placebo.

Also, those taking 500 mg were more than twice as likely to have minimal or no disability at 12 weeks following stroke vs. placebo patients as measured by the National Institutes of Health Stroke Scale.

The second Phase III trial is using the optimal dose (500 mg) identified in the first Phase III trial, said William Boni, vice president of corporate communications at Interneuron. The results of that trial should be available by late summer 1997.

In the Takeda study, citicoline was administered within three or four days following stroke at a dose of 1,000 mg per day intravenously for two weeks. The Interneuron trial administered the drug up to 24 hours following stroke.

"Although not exactly comparable in dose or duration," Boni told BioWorld Today, "the Takeda data we believe support the drug's efficacy and mortality benefit and therefore will bolster our overall new drug application."

Citicoline, a small molecule, is believed to limit the extent of the infarct, or tissue damage caused by interrupted blood flow, by preventing the accumulation of toxic-free fatty acids. It also promotes recovery of brain function by providing two components, cytidine and choline, required in the formation of nerve cell membranes.

Citicoline also promotes the synthesis of acetylcholine, a neurotransmitter associated with cognitive function.

Interneuron's two lead products, the antiobesity agent Redux and citicoline, came out of the laboratories of the company's scientific founder, Richard Wurtman, who licensed patents to both of his discoveries to foreign companies.

Redux was approved by the FDA in April 1996 and launched in June 1996.

In 1993, Interneuron acquired North American rights to citicoline from Grupo Ferrer, a Barcelona, Spain-based pharmaceutical company.

Today, citicoline is being marketed in more than 20 countries.

Interneuron, as of Dec. 31, 1996, had approximately $160 million in cash on hand. Reported loss for the year, as of Sept. 30, 1996, was $27.9 million.

Interneuron's stock (NASDAQ:IPIC) closed Tuesday at $18.875, up $0.250. *