Regeneron Pharmaceuticals Inc. suffered a serious setback Tuesday with theannouncement that it will seek FDA approval to modify and extend the PhaseIII clinical study of its lead compound, ciliary neurotrophic factor (CNTF),for the treatment of amytrophic lateral sclerosis (ALS), or Lou Gehrig'sdisease. The Tarrytown, N.Y., company said talks already are under way withthe FDA.
Company officials said they expect to finish the study by the end of theyear rather than the end of June as originally anticipated. But analystsand investors were not so sure.
Regeneron (NASDAQ:REGN) stock dropped 33 percent, down $4.38, to $8.75 pershare in heavy trading of about 1.9 million shares.
The review of the Regeneron study, conducted at the request of and inconsultation with the Data and Safety Monitoring Board and independentstatisticians, concluded that many patients who received CNTF had reactionssuch as coughing, weight loss and appetite suppression.
"For a while they do worse than the placebos," Fredric Price, Regeneron'schief financial officer, told Bioworld. "By the time they come back totolerating the drug, it's been nine months, and they don't have nine monthsto come back. The purpose of the expansion is to give us enough time toobserve if the patients have enough time to come back.
"If we found out the patients who tolerated the drug well didn't do wellon the drug, this trial would be over. (But) the people who tolerated itwell had objectively less muscle weakening than the placebos did."
Price said the company would not discuss design of the modifications fora number of reasons: Regeneron has not received FDA approval, it doesn'twant to unblind the study, and revealing modifications could be beneficialto the competition.
Synergen Inc. of Boulder, Colo., also is developing a version of CNTF andhas an ongoing patent-interference proceeding with Regeneron concerning theDNA sequence for the drug. Synergen stock closed Tuesday at $12.38, down13 cents per share.
Synergen officials, meanwhile, said they are moving forward with theirPhase III study of CNTF for ALS. More than 700 patients were enrolled inthe study in February, and completion is expected by the end of the year,said Ken Collins, Synergen's executive vice president of finance andadministration.
Collins said Synergen is dosing on a daily basis, rather than three timesper week, and is using three doses and a placebo instead of two.
Two weeks ago Vector Securities International in Deerfield, Ill., loweredits Regeneron rating from "buy" to "neutral/sell." "We feel like that wasa bullet we dodged," said Peter Drake, an analyst with Vector Securities."The risk remains that the FDA won't let them go forward; and if the FDAlets them go forward, there is a risk that protocol has been violated."But Drake said Synergen "is behind the Regeneron eight ball on this one.If Regeneron is having problems, why should one get enthusiastic aboutSynergen?"
Instead, Drake said it was a lot easier to be enthusiastic overRhone-Poulenc Rorer Inc.'s agent, Riluzole, which is being tested in onePhase III study and has completed another, which he said demonstrated areduction in mortality without a change in muscle strain. "The nature ofthe competition has changed dramatically," he said.
Regeneron's Phase II data, presented in August, showed that CNTF,administered at 30 micrograms per kilogram, slowed the rate ofdeterioration in muscle strength by 72 percent and reduced the decline intests of lung function by 44 to 69 percent in 12 patients with ALS, ascompared to 14 patients who had received a placebo.
Regeneron hopes CNTF, which has been shown in animal studies to promote thesurvival of neurons, will prove capable of doing that in patients with ALS.This fatal neurodegenerative disorder is characterized by the death ofmotor neurons. Patients become incapacitated due to loss of musclestrength and eventually die of respiratory failure.031694Regeneron
-- Jim Shrine
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