Cephalon Myotrophin NDA filing is based on two clinical trials previously discussed by FDA committee.

CEPHALON MYOTROPHIN NDA FILED FEB. 11 FOR AMYOTROPHIC LATERAL SCLEROSIS (Lou Gehrig's disease) based on the two pivotal trials previously reviewed by FDA's Peripheral & Central Nervous System Drugs Advisory Committee in June as part of the company's request for a Treatment IND. At the time, FDA and the committee agreed that Cephalon's second trial, conducted in Europe, failed to confirm the results of the first. Members of the committee suggested that an additional trial would be required for the application to be approved ("The Pink Sheet" June 17, 1996, p. 9).

Cephalon expects the NDA to receive another Peripheral & CNS advisory committee review; the next meeting of that committee has tentatively been scheduled for May 8.

Cephalon said it has provided FDA with data from open-label extensions of the Myotrophin (mecasermin) North American and European trials and hopes that the agency has a clearer picture of the findings. The European study results still do not show statistical significance in the primary endpoint, the company said.

In the North American trial, Myotrophin-treated patients had an 18-point increase in their Appel ALS score compared to a 26-point increase for placebo patients, a statistically significant result. A 20-point change on the Appel score indicates a major functional change in the ability for patients to care for themselves. In the European trial, Myotrophin showed 5.6 points less deterioration than placebo over nine months.

Myotrophin has been available under a Treatment IND approved in June ("The Pink Sheet" June 24, 1996, T&G-2). At the time of the Treatment IND approval, FDA reminded the company "of the advisory committee's view that [European] study 1202 cannot be considered an adequate and well controlled trial that demonstrates the effectiveness of Myotrophin. In particular, we urge you to take note of the fact that several members, including the chair of the committee, offered the view that the current data package would not support an approvable NDA."

Two hundred patients have received Myotrophin so far under the Treatment IND; supply of the drug is limited. Cephalon is using inventory manufactured at its Beltsville, Md. pilot plant, which was sold to North American Vaccine in October ("The Pink Sheet" Oct. 21, 1996, In Brief). Chiron, which will manufacture Myotrophin for marketing, has completed its plant but has not begun to produce significant quantities of the drug.