BETHESDA, Md. _ An FDA advisory committee on Fridayunanimously gave people with amyotrophic lateral sclerosis (ALS)something that many with the incurable disease had all butabandoned: Hope.

Hope's brand name, in this case, is Myotrophin. The recombinantinsulin-like growth factor made by Cephalon, Inc., of West Chester,Pa., is a drug that has shown promise in slowing the progression ofthe debilitating neuromuscular disease. In an unusual session, theFDA's Peripheral and Central Nervous System Drugs AdvisoryCommittee backed "treatment use of Myotrophin in patients withALS under a treatment [investigational new drug application]."

William Graney, the company's vice president for clinical operations,expressed gratitude to the committee and called its decision "animportant step forward." Company officials said Cephalon plans tosubmit a new drug application (NDA) this summer and will supplyMyotrophin free to patients participating in the company's research.

The committee's decision represents a victory for a firm that, withChiron Corp., of Emeryville, Calif., has invested $100 million todevelop a drug that has shown only moderate therapeutic activity.

Friday's session was unusual because the FDA rarely asks advisorycommittees to review a company's research before an NDA issubmitted. But, in this case, FDA asked for advisory committee helpin deciding how to interpret the scientific support the company hasamassed to justify the treatment investigational new drug (IND)application. A treatment IND will make Myotrophin widely availablepending review of the NDA.

FDA's quandry was this: Cephalon's initial study, a double-blinded,placebo-controlled trial of Myotrophin in 266 people, found the drugslowed progression of the disease by nearly 25 percent, based on arating scale validated in 1,200 patients with the disease.

European Study Dismissed By FDA

But a second trial, carried out in Europe, was far more difficult tointerpret. Although the study of 183 patients demonstrated the drugslowed progression of disease by 16 percent, FDA officials said thestudy's design was flawed and the results were not statisticallysignificant.

Graney, the vice-president for clinical operations, told the advisorypanel the North American trial demonstrated the drug's effectivenessand the European study, while inconclusive, tended to buttress thestudy's findings. Taken together, he said, the drugs "providesufficient evidence of efficacy to support treatment use ofMyotrophin in ALS."

But the FDA challenged Cephalon's findings with a withering seriesof statistical questions, dissecting the company's analysis andsubjecting it to multiple alternative tests.

In one exchange, FDA statistician David Hoberman told the panel: "Iwant you to be aware that this is not a robust result . . . A slightlydifferent analysis makes the case much less compelling."

Cephalon statistician Thomas Dobbins responded: "I don't think wecan be faulted for using the best statistical method. We believe theresults are robust."

Ultimately, the decision came down to a judgment call.

Panel chairman Sid Gilman, chairman of the department of neurologyat the University of Michigan Medical Center, in Ann Arbor,captured the concerns of many of his colleagues when he said: "Itstrikes me that we have one study that provides convincing evidenceof efficacy, and a second study that doesn't provide enough evidence.In this case, I'm inclined toward approval."

Another Study Proposed

Although the advisory committee supported the treatment IND, italso suggested another clinical study might resolve remainingquestions about Myotrophin's effectiveness.

Jason Rubin, Cephalon's vice president of corporatecommunications, said the company will discuss the possibility of athird trial with the FDA.

Myotrophin will not cure the disease, and its beneficial effects lastjust a few months. But it is only the second drug developed in the 127years since ALS was recognized that has shown even minimaltherapeutic benefit. The degenerative disease destroys motor neurons,leading to death from respiratory failure three to five years after onsetof the disorder. It affects 70,000 people worldwide and half are in theU.S.

The first drug for ALS, also is called Lou Gehrig's disease, wasapproved last year. Riluzole _ sold under the brand name Rilutek byRhone-Poulenc Rorer Inc., of Collegeville, Pa. _ prolongs survivalfor a few months but does not slow progression of the disease.

Myotrophin may or may not prolong life _ current studies were notdesigned to test survival _ but it appears to slow the progression ofdisease.

Neurologists believe that these two drugs eventually may represent aone-two punch against a disease that until last year was consideredvirtually untreatable, and remains incurable. It may also herald thedawn of an era of combination therapy.

"I think we're in a position that is analogous in many ways to theearly days of cancer therapy and AIDS," said neurologist Robert G.Miller, of California Pacific Medical Center. He added he was notinvolved in Cephalon's Myotrophin trials, but supports Cephalon'swork as a clinician who treats many patients with the disease.

Rubin noted Rhone-Poulenc has proposed collaborating on just sucha combination drug study. "We said we could consider it, but our firstpriority is to get Myotrophin approved," Rubin said.

For the 15 ALS sufferers who gathered to plead for the panel'sbacking, even a minimal benefit is better than nothing. "One hundredtwenty seven years is a long time to wait," said Frank Micale, an ALSsufferer from Wilmington, Del., who has a wife and two children,ages 4 and 10. "I would like to go home today and tell my son anddaughter and fellow ALS patients that another drug is available." n

-- Steve Sternberg Special to BioWorld Today

(c) 1997 American Health Consultants. All rights reserved.