The FDA on Monday approved the use of Myotrophin under atreatment investigational new drug program that will make the drugavailable to amyotrophic lateral sclerosis (ALS) patients before it isapproved for marketing.
The clearance, coming after a unanimous recommendation of anadvisory panel earlier this month, was expected by most, even thoughquestions remained from one of two pivotal studies of the drug. Thelarger issue now is whether the FDA will require another pivotalstudy before granting approval of the recombinant human insulin-likegrowth factor, said Tim Wilson, an analyst at UBS Securities in NewYork.
"Everyone agrees a new trial will be needed," Wilson said, predictingthat study would be a post-approval Phase IV trial rather than anotherpivotal study. He speculated the Phase IV might involve Myotrophinand Rilutek, the only approved ALS drug, in studies comparing theagents against each other and in combination.
Cephalon Inc., of West Chester, Pa., and Chiron Corp., ofEmeryville, Calif., are collaborating on development and marketingof Myotrophin. They have said filing of a new drug application(NDA) is expected this summer.
Jason Rubin, vice president, corporate communications for Cephalon,said no date has been set for the official launch of the treatment INDprogram. "We'll provide Myotrophin to as many patients aspossible," he said. "Initially we expect it will be a small program dueto limited drug supply, and we'll expand the program as suppliespermit."
Cephalon and Chiron will offer Myotrophin free of charge under thetreatment IND. Patients could be switched over to a payment systemonce the NDA is approved.
Rubin, like Wilson, said there are ethical concerns about runninganother placebo-controlled study after approval of the treatment IND.
Since the drug is available under the program, and has shown benefitin slowing progression of the disease, it could be considered unfairand inhumane to the ALS patients who receive placebo. A lot ofpatients would die while waiting for trial results, Wilson said.
ALS, or Lou Gehrig's disease, is a degenerative neuromusculardisease that destroys motor neurons, leading to respiratory failure anddeath within a few years. It affects about 70,000 people worldwide.
On June 7, 1996, the FDA's Peripheral and Central Nervous SystemDrugs Advisory Committee recommended that the agency clearMyotrophin under the treatment IND program. It was an unusualsession because a panel rarely is asked to review a drug before anNDA submission. (See BioWorld Today, June 6 and 10, 1996, p. 1.)
The first of two pivotal studies, a 266-patient trial in the U.S.,showed the drug slowed progression of ALS. Results were not soconclusive, however, in a 183-patient study in Europe, the FDA saidat the panel meeting.
Rubin said Cephalon officials told panel members they "were notprepared to undertake another pivotal Phase III study, and wouldpropose instead to conduct a Phase IV combination study withMyotrophin and riluzole."
Riluzole, a small-molecule compound, is marketed under the nameRilutek by Rhone-Poulenc Rorer Inc., of Collegeville, Pa. The drug,approved in December 1995, prolongs survival for a few months butdoesn't slow disease progression. Some physicians said acombination of Myotrophin and Rilutek could be better than eitheragent alone. n
-- Jim Shrine
(c) 1997 American Health Consultants. All rights reserved.