Cambridge NeuroScience Inc. is aggressively pursuing clinicaltrials of its lead neuroprotective agent Cerestat in head injurypatients with enrollment this month in the U.S. and the UnitedKingdom.

The Phase Ib trials are designed to test safety and dosing of thesmall molecule, an NMDA channel blocker, in brain-injuredpatients. Ongoing Phase Ib trials of Cerestat in stroke patientshave indicated that the compound is well-tolerated, said ElkanGamzu, president and chief operating officer. Stroke patientshave reached the second dose in the ascending dose, placebo-controlled trial.

A separate trial is called for in head injury patients becausethey tend to be younger, healthier accident victims. Mostvictims of traumatic brain injury are younger than age 30 andreceive their injuries in car accidents. The majority of peoplewho suffer stroke, meanwhile, are over age 65.

Gamzu said the investigators believe that head injury patientsmay tolerate higher doses of Cerestat, which is deliveredintravenously and was shown in preclinical models to cross theblood-brain barrier and rapidly clear the bloodstream. (Anarticle on this work appeared in the February issue of thejournal Neurology.)

Also, because head injury is a severe indication that sends onlyabout 500,000 Americans to the hospital annually, he saidclinical trials may be moved along more quickly. CambridgeNeuroScience may attempt to enter a pivotal Phase II trial in1994 based on results of the Phase Ib study.

Gamzu believes the Cambridge, Mass., company's closestcompetitors are Roche Laboratories and Ciba-Geigy AG, whichare developing compounds to affect the glutamate NMDApathway that leads to death of neurons from interrupted bloodflow in the brain.

"We're catching up very rapidly; we're a smaller company andit's higher priority for us," he said.

Also, The Upjohn Co. and Sterling Winthrop Inc. have beendeveloping Lazaroids and PEG-SOD, respectively, whichintervene later in the cascade after neurons are broken downby absorbing excess calcium ions.

Gamzu said Cambridge NeuroScience (NASDAQ:CNSI) has "lessconstraint on resources" since it decided earlier this month tohalt development of Ectapram as an adjunct toelectroconvulsive therapy. That decision, based on marginalefficacy shown in a Phase II/III trial, should free an estimated$10 million over the next 18 months to use on clinical trialsand other purposes.

The head injury trials are taking place at Hermann Hospital, aregional trauma center associated with the University of TexasMedical School at Houston, and the Southern General Hospital ofthe University of Glasgow in Scotland.

Neurosurgeon Guy Clifton, who is directing the Cerestat trial atHermann Hospital, said Cerestat "may have the ability to arrestthe secondary biochemical cascade that occurs after the originaltrauma." This series of secondary metabolic events is believedto be the cause of additional long-term damage after the initialhead injury.

Of the 500,000 Americans who suffer severe brain trauma eachyear, about 100,000 die. About 80,000 survivors remainpermanently disabled with an average annual treatment cost of$45,000. Stroke also affects about 500,000 people in the U.S.each year.

The company's newly appointed vice president of clinicalstudies, Heikki Hakkarainen, was previously executive directorof CNS clinical research at Ciba-Geigy Corp. and has also beenchief of a Finnish neurology clinic.

-- Nancy Garcia Associate Editor

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