Interneuron Pharmaceuticals Inc. will meet with the FDA beforedeciding whether Phase III data on its stroke drug is sufficient forfiling.
The company reported further details Thursday from citicolineshowing the lowest (500 milligram) and highest (2,000 milligram) ofthree doses tested produced statistically significant benefits for thosein the 259-patient, placebo-controlled, double-blind study. It appearsthe 500 mg dose will be the one taken forward.
The company's stock (NASDAQ:IPIC) gained 11 percent Friday,moving up $3.63 to close at $37.13.
"We intend to meet with the FDA very soon and decide on anapproval strategy," said Bobby Sandage Jr., Interneuron's executivevice president of research and development. Regardless of the filingdecision, he said, the company plans to start a large trial in a monthor so measuring 500 mg of citicoline against placebo.
Citicoline, a small molecule, already is being marketed in Japan andparts of Europe for stroke and head trauma. The drug was discoveredby Richard Wurtman, Interneuron's scientific founder and director ofthe Clinical Research Center at the Massachusetts Institute ofTechnology, and licensed to Grupo Ferrer, of Barcelona, Spain.Interneuron, of Lexington, Mass., acquired a license to citicoline inthe U.S. and Canada in 1993.
The molecule is believed to have a dual mechanism of action. As aneuroprotectant, it may stabilize membranes so they don't get anaccumulation of free fatty acids, Sandage said. The neurorepairaspects come about because the drug provides the main ingredientsfor cell membrane generation, he said.
Another study testing the drug's ability to limit infarct size already isunder way. That came about after analysis of a subgroup of patientsconducted at Beth Israel Hospital in Boston suggested citicolinelimited infarct size following interrupted blood flow.
Data from the Phase III study "are very consistent with what theyfound in Japan and Europe," Sandage said, adding that theinvestigational new drug application Interneuron submitted to run thetrial contained data on more than 11,000 patients. The outcomescales used in the U.S. are not exactly the same as used elsewhere,however.
Drug Provides Flexibility
In the study patients were enrolled within 24 hours of the onset ofsymptoms, a much longer window than is being used with other drugsunder development. The primary efficacy outcome was improvedneurologic function as assessed by the Barthel Index, which uses a100-point rating scale.
Among those who received 500 mg of citicoline daily 53 percentachieved a Barthel Index score of 95 or more at 12 weeks, comparedwith 33 percent of placebo patients. Patients in the 500 mg groupachieved complete or near-complete recovery two weeks faster thanthose taking placebo.
Also, those taking 500 mg were more than twice as likely to haveminimal or no disability at 12 weeks following stroke vs. placebopatients, as measured by the NIH Stroke Scale. Using anothermeasurement, the Rankin Scale, global neurologic status wassignificantly improved with citicoline vs. placebo.
The middle citicoline dose of 1,000 mg did not reach statisticalsignificance. Researchers said the higher body weight of those in thatgroup may be one of the reasons for that result.
"Findings from this trial with citicoline reflect a similar degree ofefficacy to that of the clot-dissolving drug, t-PA, reportedpreviously," Wayne Clark, director of the Stroke Center at OregonHealth Sciences University, said in a prepared statement. "The broadwindow of treatment opportunity for citicoline, up to 24 hours post-stroke, combined with its oral dosage form and its well-toleratednature suggest that citicoline may be the most practical treatmentcurrently under development for stroke."
Genentech Inc., of South San Francisco, markets t-PA under thename Activase. The drug already is approved for myocardialinfarctions. The company filed a supplement to its product licenseapplication on March 18, 1996, seeking approval to market the drugfor stroke. Studies in that indication showed t-PA was most effectiveif given within three hours of a stroke.
On Thursday Cambridge NeuroScience Inc., of Cambridge, Mass.,presented data showing a high dose of its N-Methyl-D-Aspartate ionchannel blocker, Cerestat, had benefit in stroke patients. Thecompany and corporate collaborator, Germany-based BoehringerIngelheim GmbH, are planning pivotal studies.
Both the Cambridge NeuroScience and Interneuron data werepresented at the American Academy of Neurology meeting in SanFrancisco. n
-- Jim Shrine
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