By Lisa Seachrist

Washington Editor

WASHINGTON — The FDA has issued an approvable letter for Myotrophin as a treatment for amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, to the drug's developers, Cephalon Inc. and Chiron Corp.

In issuing the letter, the agency has said it will approve Myotrophin, an injectable recombinant human insulin-like growth factor-1, once the companies have met several conditions.

What is normally good news appears to have left the companies, investors and patients in limbo, with the prospects for the drug's approval as dimly understood as they were before the agency's announcement.

Cephalon's stock (NASDAQ:CEPH) faltered on the news that its lead drug candidate received an approvable letter from the FDA, falling $3.375 to close at $11.375.

Much of the confusion over the drug's status comes from the fact that the letter stated Myotrophin was "potentially approvable" and noted that the FDA wanted Cephalon and Chiron to submit additional information from ongoing trials which demonstrate Myotrophin is effective in the treatment of ALS. The companies intend to meet with FDA as soon as possible to find out exactly what type of information is needed.

"The letter appears to be somewhat different from what we understand an approvable letter to be," said Jason Rubin, vice president of corporate communications for West Chester, Pa.-based Cephalon. "We are anxious to meet with FDA as soon as possible. We would hope to be able to define the path forward for Myotrophin."

Myotrophin is currently being studied by Cephalon's Japanese partner, Kyowa Hakko. That trial is planned to involve 180 patients and is expected to complete enrollment this year and provide results sometime next year. In addition, the company is following long-term outcomes from a European trial. Although not designed as a data collection protocol, the company is also providing Myotrophin to 400 ALS patients as part of a treatment investigational new drug (IND) program.

While data may be gleaned from these active protocols, Myotrophin's success lies with the strength of the information that the agency is requiring. Felecia Reed, an analyst with Cowen & Co., in Boston, said there is a difference between proving that a drug is efficacious and showing that it doesn't harm people.

"The FDA routinely asks for additional efficacy data when they send a non-approvable letter," Reed said. "Does the agency want additional efficacy data or do they need evidence that the ongoing trials show nothing bad? Cephalon needs to get that question answered before they can tell us what kind of time frame to expect with Myotrophin."

No Deadline Set For Final FDA Ruling

Reed also noted that because the agency met its statutory deadline under Prescription Drug User Fee Act by issuing the approvable letter Tuesday, the agency no longer has a deadline to review additional efficacy data and to clear Myotrophin for marketing. In essence, Reed said, the agency issued a non-decision and left Myotrophin in limbo.

"The saga continues," Reed said.

Myotrophin has a had a particularly bumpy ride. In June 1996, an FDA advisory panel approved the company's request for a treatment IND for ALS, a progressive and fatal neurodegenerative disease that destroys motor neurons. That decision was based on an American study that showed Myotrophin slowed the progression of ALS by 26 percent compared with placebo. However, because a European study failed to show any benefit from treatment with Myotrophin, the panel recommended the companies use the treatment IND to conduct another study. The companies did not heed that advice.

In May 1997, the same advisory panel refused to recommend Myotrophin for approval, citing conflicting trial results. At that time, the agency was bound to decide Myotrophin's fate by August 11, 1997. At the FDA's request, Cephalon and Chiron submitted supplemental information for Myotrophin, setting back the clock by three months to Nov. 11, 1997. As that deadline approached, the FDA needed still more time to make its decision, so the companies withdrew and resubmitted the NDA, adding six more months to the clock.

The agency scheduled yet another panel meeting for the drug in early April, but canceled the meeting at the last minute. Tuesday the FDA sent the approvable letter to Cephalon and Chiron.

Throughout these events, ALS patients and their families have been actively lobbying the agency to approve Myotrophin. Currently the only drug approved for ALS is Collegeville, Pa.-based Rhone-Poulenc Rorer Inc.'s Rilutek, which has been shown to add an average of three months of life for ALS patients, whose life span after diagnosis averages three years.

ALS Association Official Optimistic

"We are taking an optimistic outlook on this news," said Carol Levey, vice president of marketing for the ALS Association. "Yet we know that we have ALS patients who are acutely aware that this is just another delay for Myotrophin. The only hope we have is that the drug stays in play."

Levey also noted that the letter calls into question continued access for patients who are currently receiving Myotrophin as part of the treatment IND. Cephalon has stated it will continue to provide drug for the expanded access program; however, the long-term prospects of that program will be determined by the agency, not the company.

Of greatest concern to Levey is the message the FDA may be sending to companies that are currently developing therapies for ALS.

"We fear that this may give other companies pause in regard to developing ALS treatments," Levey said. "We don't want this to slow new therapies. ALS patients don't have time on their side."

But ALS patients may soon have Congress on their side. The ALS Association is on Capitol Hill today to raise awareness about the disease and lobby for increased National Institutes of Health funding for research into the disease.

"Myotrophin will be part of our discussions with the members of Congress," Levey said. "We have to remain hopeful."

The stock of Emeryville, Calif.-based co-developer Chiron (NASDAQ:CHIR) closed at $20.4375 down $0.25. *

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