Interneuron Pharmaceuticals Inc. Tuesday responded to the FDA'sFebruary rejection of the company's anti-obesity drug, dexfenfluramine, by submitting two new clinical studiesaimed at countering the agency's concerns over potential side effects.
Three months ago, the FDA sent Interneuron, of Lexington, Mass., anon-approvable letter for its new drug application (NDA) fordexfenfluramine. The agency was worried about the risks of primarypulmonary hypertension (PPH) and neurotoxicity in taking theprescription drug. (See BioWorld Today, Feb. 24, 1995, p. 5.)
Interneuron officials said they expected the FDA's action and wereprepared to submit additional studies addressing the concerns.
One study, examining the pulmonary hypertension issue, wassponsored by the Paris-based pharmaceutical company, LesLaboratoires Servier, which discovered dexfenfluramine and marketsit in Europe.
The second study on potential neurochemical changes was conductedby Interneuron in the Boston area.
Dexfenfluramine is marketed in 50 other countries and has been onsold in Europe for 10 years. The drug stimulates release of serotonin,a neurotransmitter, which curbs appetite centers in the brain.Interneuron licensed rights to dexfenfluramine from Servier in 1992.
William Boni, Interneuron's director of corporate communications,said the PPH study was conducted over two years and presentation ofthe data is expected in August. The results also are being reviewed byEuropean regulatory authorities.
The investigators said there was a "four-fold increase in the risk ofPPH in the treated patients reviewed," but no specific connection todexfenfluramine was found. In the general population, PPH, a seriousdisorder, reportedly affects up to two people per million each year.
The European study concluded "the condition of obesity itself, theuse of a group of anorectic weight-loss drugs, includingamphetamines and non-amphetamines, and systemic hypertension"may be factors in the increased risk of PPH.
Interneuron said the French Drug Agency has advised doctors aboutthe PPH study and "delineated prescribing guidelines for anorecticweight-loss drugs," which would include dexfenfluramine.
Interneuron began its study of possible neurotoxic effects last fall inresponse to research conducted by Johns Hopkins University, ofBaltimore, and published in May 1994. The findings suggesteddexfenfluramine caused adverse changes in the brains of monkeys.
Interneuron said it conducted trials in humans and no potential forneurotoxicity was found. Boni said the data will be submitted forpublication at an undisclosed date.
The FDA has 180 days to respond to Interneuron's submission of thetwo new studies. During that time the company expects to meet withan advisory panel of the agency to discuss approval of the drug.
The NDA for dexfenfluramine was submitted to the FDA in May1993. Interneuron said the application included safety and efficacydata from 18 clinical trials involving more than 4,500 patients.
Interneuron's stock (NASDAQ:IPIC) closed Tuesday up 37 cents to$7.87. n
-- Charles Craig
(c) 1997 American Health Consultants. All rights reserved.