SILVER SPRING, Md. _ The FDA's Endocrinologicand Metabolic Drugs Advisory Committee reluctantlyvoted 6-5 late Thursday to recommend approval of thefirst new anti-obesity drug in the U.S. in two decades.
Dexfenfluramine hydrochloride (Redux) is manufacturedby Interneuron Pharmaceuticals Inc., of Lexington, Mass.
The vote marked the culmination of a highly unusualsecond meeting on the drug. The first meeting on Sept.28, 1995, ended in disarray when a number of advisorycommittee members left before the votes were finalized,forcing the FDA to reschedule another meeting. (SeeBioWorld Today, Sept. 29, 1995, p. 1.)
After narrowly recommending approval, the committeevoted unanimously to urge the FDA to require a Phase IVpost-marketing surveillance study of sufficient strengthand duration that rare clinical events such as pulmonaryhypertension and neurological toxicity could be isolated.
If approved by the FDA, dexfenfluramine would be thefirst drug approved to treat obesity on a long-term basis.
Interneuron's second presentation sharpened thediscussion of neurotoxicity data which had concernedseveral panel members at the September meeting. Inaddition, the company presented new data showing thattreatment guidelines for the drug had recently beenchanged by the French health ministry to permit long-term use.
While dexfenfluramine promises to generate millions ofdollars in revenues for Interneuron and its marketingpartner, Wyeth-Ayerst, of Philadelphia, the panel did notview the drug as "breakthrough," according to RobertKreisberg, director of internal medicine at Baptist HealthSystem, in Birmingham, Ala.
"This drug is effective for a subset of patients. Butobesity is a condition that involves a spectrum ofconditions," Kreisberg said. The drug has "limited effectand physicians should discontinue its use if they find noeffect."
"I don't want this seen as a magic bullet," said Jose Cara,head of endocrinology at Henry Ford Hospital, in Detroit."The drug's success rate is much less than what thepublic anticipates."
Labeling proposed by the company focused on morbidlyobese people. Interneuron proposed that the drug beindicated for people on a low-calorie diet who had a bodymass index over 30 or those with a body mass index over27, but who also had co-morbidities such as hypertensionand diabetes.
Several panel members were impressed with data fromFDA medical reviewer Leo Lutwak who could confirmonly a 3 percent weight loss associated with the drug. Hediscounted effects raised by Interneuron scientists whichshowed the drug lowered blood lipids, indicating the drughad an hypercholesterolemia effect.
Anticipating the committee's final vote, FDAepidemiologist Bruce Stadel earlier in the eveningpredicted that the considerable publicity surrounding thedrug would prompt physicians to readily report suspectedcases of pulmonary hypertension. But he added that anadequately designed Phase IV study would provide hardevidence of benefits and risks.
Several panel members were concerned thatdexfenfluramine would be abused by young womenanxious to keep their weight down to compete incompetitive sports and arts such as gymnastics and ballet.There was considerable nodding of heads around the tablewhen several panel members said there was a "potentialfor misuse" of the drug among young women. They urgedthe company to conduct a physician and patient educationcampaign to clarify the population for which the drugwould be indicated.
Interneuron's stock (NASDAQ:IPIC) closed at $15.50,down 6 cents Thursday before the panel made itsdecision. Following the first meeting in September, thecompany's stock was at $11.50. In May 1993, just after anew drug application was filed for dexfenfluramine,Interneuron's stock traded at $8.75. n
-- Michele L. Robinson Washington Editor
(c) 1997 American Health Consultants. All rights reserved.