By Lisa Seachrist

Washington Editor

WASHINGTON — Amidst the backdrop of impassioned pleas from patients and their physicians, an FDA advisory panel voted 6-3 to recommend that the agency not approve Cephalon Inc.'s Myotrophin for treatment of amyotrophic lateral sclerosis (ALS).

Citing equivocal clinical results, the Peripheral and Central Nervous System Drug Advisory Committee determined there simply wasn't enough evidence to show that Myotrophin (recombinant human insulin-like growth factor-1) had an effect on the progression of ALS, which also is called Lou Gehrig's disease.

"I don't think the strength of the Myotrophin data from the [North American] trial is adequate to recommend approval," said Sid Gilman, panel chairman and head of neurology at the University of Michigan Medical Center in Ann Arbor. "It's an extremely difficult decision to make."

The same panel approved a treatment investigational new drug (IND) application for Myotrophin in June 1996 based on data showing the drug slowed progression of the disease by 26 percent and in light of another trial, conducted in Europe, that failed to show statistically significant results. Under the treatment IND, Myotrophin has been available to ALS patients pending the FDA's review.

Cephalon, of West Chester, Pa., and its Myotrophin development partner, Chiron Corp., of Emeryville, Calif., bolstered their new drug application with data showing Myotrophin prolonged survival by three months and had a dose response. The companies also provided biological underpinnings for the activity of Myotrophin. They maintained the impact of the drug was far from modest.

"If one drives 26 percent slower, it takes 35 percent longer to get to any destination," said Robert Miller, chairman of the department of neurology at the California Pacific Medical Center in San Francisco. "That means a 35 percent slower time to clinical manifestations of ALS, such as inability to speak clearly, eat solid foods and walk."

More Than One Successful Study Needed

FDA officials, however, questioned whether positive results from a single trial were strong enough to support approval.

"Wishing that Myotrophin has an effect is not enough," said Paul Leber, director of the agency's division of neuropharmacological drug products. "In the face of a negative trial it is hard to say that the North American trial is substantial evidence."

While biostatistician Chris Gennings, from the Medical College of Virginia, agreed that the data did not present the strongest evidence of effectiveness, she noted the agency may be asking for too much proof.

"I think that perhaps the ALS community is willing to accept a lower standard of evidence," she said. "I think Myotrophin is a special case and it should be approved."

FDA is not bound by the decision of its advisory panels, but the agency usually follows their recommendations.

About 70,000 people worldwide, more than half of them in the U.S., suffer from ALS. The neurodegenerative disease destroys motor neurons, leading to loss of muscle control and death from respiratory failure. It usually kills victims in three to five years.

Trading in the stocks of Cephalon (NASDAQ:CEPH) and Chiron (NASDAQ:CHIR) was halted Thursday. *