BOSTON -- Monday was a double-header day for InterneuronPharmaceuticals Inc., which reported key events for its twolead products, both dietary supplements.
Glenn Cooper, the Lexington, Mass., company's president andchief executive officer, told a luncheon meeting of the BostonStockbrokers Club here that the company was launching"Hearty Balance," a specially formulated mix of protein andcarbohydrate to correct imbalances in the protein intake ofpatients with Parkinson's disease.
In Milwaukee, meanwhile, Thomas Marbury of the Orlando,Fla., Clinical Research Center, which conducted a clinical trial ofInterneuron's anti-obesity drug, dexfenfluramine, told theNorth American Association for the Study of Obesity that hisstudy had identified the dosage level with the most efficacyand fewest side effects (usually dry mouth and mild diarrhea).
In both cases, the dietary products act by modulatingmolecules secreted in the brain PP dopamine for Parkinson's,serotonin for appetite control.
Dexfenfluramine stimulates the release of the neurotransmitterserotonin into the synapse and inhibits its re-uptake. So does ahearty meal of fats and carbohydrates, the twin nemeses ofoverweight and obese people, who eat their fill of these sinfulsubstances. That "fill" is a sensation mediated by serotonin. Itspre-satiation release by dexfenfluramine, Cooper told theBoston brokers, curbs the craving for carbohydrates and thuslimits weight gain while maintaining protein intake.
He described 18 double-blind, placebo-controlled clinical trialsinvolving some 3,400 volunteers in France and 600 in the U.S.who swallowed graduated doses of the prescription drug whileon a semi-starvation diet of 1,200 calories. At all three doselevels, subjects lost markedly more weight than cohorts takinga placebo pill.
Marbury reported that both the 15-and 30-mg dosageregimens produced an average weight loss of 5 kilograms (11pounds) after 12 weeks of use, nearly three times as much asthe 2 kilos shed by the placebo group.
In Milwaukee, the obesity association heard that the mediandose of dexfenfluramine, 15 milligrams twice daily, "was foundto offer the best combination of weight reduction and patientacceptance," when compared with 30- and 5-mg doses.
People in 40 countries -- 5 million in France alone -- arealready customers for the drug, for which Interneuron filed anew drug application with the U.S. FDA on May 24 (seeBioWorld, May 25).
Meanwhile, American Cyanamid/Lederle Laboratories hasconcluded a financial alliance with Interneuron in anticipationof the drug's eventual approval. It has already givenInterneuron $8 million, with $9.5 million in prospect followingNDA approval.
During 1992, Cooper reported, France, with a population of 50million, generated about $100 million in dexfenfluramine sales.With five times the population and more obesity, he observed,"the U.S. market for dexfenfluramine will be significant."
"Hearty Balance," the Parkinson's nutritional product, wasbrought to market Monday by Elan NutraPharma of Cambridge,Mass., a division of Elan Corp. plc of Athlone, Ireland. Elan inturn is an Interneuron licensee.
"The product's mode of action is quite simple and fascinating,"Cooper told BioWorld. In dietary protein breakdown, heexplained, one of the classes of amino acids that are liberatedwhen protein is digested are so-called "large neutral aminoacids (LNAAs)," (including iso-leucine, leucine, methionine,phenylalanine, tryptophan, tyrosine and valine.)
These LNAAs are structural analogs of L-dopa, the drug thatParkinson's patients take regularly to restore their brain'sfailing output of dopamine and relieve their muscularsymptoms.
Dopamine is also an LNAA, and it actually competes for bindingsites with the dietary LNAAs, across the blood-brain barrier.Consequently, dopamine has reduced access to the binding sitesand reduced saturation. This results in undermedication, whichcan cause acute exacerbation of a patient's Parkinsoniansymptoms, notably muscle rigidity.
The "Hearty Balance" food product has a specific ratio ofproteins and carbohydrates, which results in only a modest risein these LNAAs, thus giving better receptor access to L-dopa.
Queried as to what diet supplements have to do withbiotechnology, Cooper replied, "Commercialization of a productcoming from a bio-pharmaceutical company, I think, isworthwhile in and of itself, even though it's not a classicrecombinant protein."
He added: "Any biotech companies that have predictableroyalty-stream revenues are differentiated from others. This isa program that's going to help us fuel a lot of the moretraditionally oriented biotechnology programs that we dohave."
These, as he described at the meeting in detail, include twosubsidiaries, Progenitor Inc. and Transcell Technologies Inc.One is developing technologies related to stem-celltherapeutics, the other to drug transport across cellmembranes.
On its own, Interneuron (NASDAQ:IPIC) is developingCiticholine, a key brain chemical, as a potential treatment tohasten recovery of patients from stroke and head trauma.
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.