Phase II clinical trial data on Regeneron Pharmaceutical Inc.'sciliary neurotrophic factor (CNTF) for treating amyotrophiclateral sclerosis (ALS) were presented Tuesday at the WorldCongress of Neurology Meeting in Vancouver, B.C.

Lead investigator Benjamin Rix Brooks, director of the ALSClinical Research Center at the University of Wisconsin-MadisonMedical School, presented the safety and efficacy data. Thosedata show that CNTF, administered at 30 micrograms perkilogram, slowed the rate of deterioration in muscle strengthby 72 percent and reduced the decline in tests of lung functionby 44 to 69 percent in 12 patients with ALS, as compared to 14patients who had received a placebo.

The high dose of CNTF reduced the decline in one measure oflung function called forced vital capacity (FVC) by 44 percentversus placebo. That same dose--30 micrograms--also reducedthe rate of decline in a second measure of lung function calledpeak inspiratory flow (PIF) by 69 percent versus placebo.

Six doses of CNTF were used in the trial--from 0.5 to 30micrograms per kilogram. All six doses were safe and well-tolerated during the trial; they were administered viasubcutaneous injection three times weekly on an outpatientbasis for up to 20 weeks, explained Brooks. A total of 55patients were enrolled in the Phase II trial.

Four deaths were reported in the study--two patients in theplacebo group and two who received drug (but not in the 30microgram arm), according to Regeneron's president and chiefexecutive officer Leonard Schleifer. He added that all thedeaths were attributed to disease progression. All survivingpatients, including those in the placebo group, were put ontherapy with CNTF at the end of the trial.

Anti-CNTF antibodies were detected in all patients treatedduring the trial at dose levels of 3 micrograms per kilogramand higher, but Schleifer said it's not clear yet whether thepresence of antibodies is "good or bad;" that depends on "how itaffects the clinical outcome."

The hope is that CNTF, which has been shown in animal studiesto promote the survival of neurons, will prove capable of doingjust that in patients with ALS, or Lou Gehrig's disease. Thisfatal neurodegenerative disorder is characterized by the deathof motor neurons. Patients become incapacitated due to loss ofmuscle strength and eventually die of respiratory failure.

According to lead investigator Brooks, "Although the smallnumber of patients involved in this Phase II trial precluded usfrom determining the effect of CNTF at the 95 percent level ofprobability, we can say with a probability of between 80 and92 percent that the effects we saw in the patients treated withthis dose [30 micrograms] of CNTF were due to theadministration of the drug."

Regeneron of Tarrytown, N.Y. first announced the results of itsPhase II trial in an abbreviated version via press release onAug. 9. At that time, Regeneron (NASDAQ:REGN) indicated thatwhile CNTF was safe and well-tolerated, it did not slow rates ofdisease progression to a statistically significant level whencompared with the placebo. Because Regeneron was in its quietperiod vis a vis a secondary public offering (which completedAug. 26, at a price of $14.75 per share), it could make nofurther public comment on the data.

Wall Street, which had been anticipating encouraging data,reacted negatively, and Regeneron's stock fell from $18.25 (onJuly 30) to $15.50 (on Aug. 13.) Apparently investors wereanticipating Tuesday's result reporting, as well. The stockclosed Friday at $18.13 but lost $1.38 Monday, closing at$16.75.

At the time, Kevin Wilson, an analyst who follows Regeneronfor S.G. Warburg & Co. Inc., downgraded his rating on thecompany to a hold, which he still maintains. Though hebelieves the company has "very good science," Wilson iswaiting for the Phase III results on CNTF. "No conclusions canbe drawn from the Phase II data about what the 700-patientPhase III trial will show," he said.

Those Phase III trials are actually under way -- the companyinitiated them in March 1993. The double-blind, placebo-controlled pivotal trial is being conducted at 36 clinical centersin 720 patients. One third of them are receiving the 30microgram dose of CNTF; one-third are being dosed with 15micrograms; and the other segment is receiving a placebo.

-- Jennifer Van Brunt Senior Editor

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