A report on potential toxicity of an appetite suppressant beingdeveloped by Interneuron Pharmaceuticals Inc. is not affectingthe company's plans to file for U.S. marketing approval by theend of 1992.
Johns Hopkins University researchers and a colleague at theNational Institutes of Health reported in the Dec. 14 issue ofThe Lancet that dexfenfluramine damages certain nerve cells inthe brains of monkeys given the drug. But Interneuronexecutives told BioWorld that the findings have not beenaccepted by other scientists.
"We've met with the FDA a couple of times" in preparing a newdrug application for dexfenfluramine, said Charles Casamento,president and chief executive. "One of the meetings concernedthis issue, and we are proceeding" with the NDA, he said.
Interneuron (NASDAQ:IPIC) of Lexington, Mass., is counting ondexfenfluramine to provide revenues while the companydevelops other products.
The drug's chemical parent, fenfluramine, has been in humanuse for 20 years and dexfenfluramine has been sold in Europefor five years. "Six to 7 million patients" have used the drugwithout problems, Casamento said. Interneuron obtained U.S.rights to dexfenfluramine from its French marketer, LesLaboratoires Servier.
The drug is believed to act on nerve cells containing themessenger serotonin by mimicking the serotonin signal ofsatiety that is usually triggered by the intake of fats andcarbohydrates.
The Hopkins report claims that the serotonin signal sent bydexfenfluramine kills the messenger's cells. Toxicity ofdexfenfluramine and fenfluramine was first seen in rats, butthe Hopkins scientists then turned to monkeys for furtherevidence because these animals metabolize the drugs in amanner similar to humans.
The toxicity was dose-related and more apparent in themonkeys than it had been in rats, the researchers reported.The dose in monkeys "is only about five times that typicallyprescribed to patients," the researchers reported. "We believecaution is necessary in the clinical use of dexfenfluramine,"they said.
Massachusetts Institute of Technology neuroscientist RichardWurtman, a consultant and co-founder of Interneuron, didoriginal work that led to the university's patent ondexfenfluramine as an obesity treatment, which was licensed toServier. He told BioWorld that the evidence used by theHopkins researchers is weak and can be explained by thepharmacologic action of the drug.
The action of dexfenfluramine to increase levels of serotoninoutside nerves and decrease it inside nerves would show up asa histochemical loss of nerve fibers, like the one described inthe Lancet paper. The effect is fully reversible, as has beendemonstrated by other researchers, Wurtman said.
Wurtman said he and other scientists have prepared a rebuttalin a letter sent to the Lancet editors.
Interneuron stock climbed $1 to $9 on Monday.
-- Roberta Friedman, Ph.D. Special to BioWorld
(c) 1997 American Health Consultants. All rights reserved.