Genetics Institute Inc. and its research spinoff, SciGenics Inc.,announced Tuesday that FDA has finally given them the nod tobegin human clinical trials on macrophage-colony stimulatingfactor (M-CSF) for lowering cholesterol.

GI (NASDAQ:GENIZ) still needs to complete its final siteselection and get institutional review board approvals, butplans to start the trials in the first half of this year, accordingto Dennis Harp, the Cambridge, Mass., company's director ofcorporate communications.

Approximately 500,000 people in the U.S. suffer from familialhypercholesterolemia (FH), the genetic predisposition toseverely high blood serum cholesterol levels. Of these, a smallsubset has life-threatening levels of cholesterol; they will bethe subjects of GI's trial on M-CSF.

This study in humans had been on hold until GI satisfactorilyanswered the questions that FDA raised last August about GI'sinvestigational new drug application (IND). GI filed its amendedprotocol last fall. "We haven't been discussing the nature of theFDA questions," Harp told BioWorld, "but we've provided FDAwith the additional data and information that answered theirquestions."

GI found that M-CSF might lower cholesterol levels duringearlier clinical trials on M-CSF in normal healthy volunteers(Phase I safety trials) and on cancer patients (in whom itstimulated macrophage activity in Phase II trials), explainedHarp. Individuals in both groups had normal cholesterol levels,which were reduced during the administration of M-CSF. Thecholesterol counts returned to the previous levels when the M-CSF treatment was discontinued.

As well, GI scientists had found that M-CSF lowered cholesterollevels in animal models of hypercholesterolemia. "Our studiesof M-CSF in a relevant model of FH in rabbits suggests that thispharmacologic approach may be beneficial," said Patrick Gage,GI's executive vice president.

"M-CSF's mechanism for lowering cholesterol appears to bedifferent from the mechanism used by existing approveddrugs," Harp explained.

One of those approved drugs is Merck & Co. Inc.'s Mevacor(lovastatin), which inhibits HMG-CoA reductase, an enzymevital to the liver's manufacture of cholesterol. By inhibiting theenzyme, the drug results in decreased cholesterol synthesis bythe liver. The biological mechanisms "may also induce the LDLreceptor, leading to reduced production or increased catabolismof LDL cholesterol," according to the West Point, Pa.,pharmaceutical company.

Mevacor is intended for treating patients whose low-densitylipoprotein (LDL) cholesterol levels "put them at significant riskof developing cardiovascular disease," according to Merck,including 60 percent of the patients enrolled in the clinicaltrials on Mevacor, who suffer from familialhypercholesterolemia.

And other drugs currently approved for treating highcholesterol employ resins that bind cholesterol -- or the lipidsand fats that the body converts into cholesterol -- in the smallintestine or the colon, preventing it from being absorbed intothe body, Harp explained.

Another drug being studied for reducing cholesterol is CP408, aproduct of Cibus Pharmaceutical Inc. The privately heldRedwood City, Calif., company filed an IND for Phase II trials onCP408 with FDA last week. CP408 is niacin (a B vitamin)combined with the company's Geltrx drug delivery system, apatented novel blend of natural plant fibers.

"Niacin is recommended by the NIH as the drug of choice --after diet -- for lowering triglycerides and increasing HDL("good" cholesterol)," said Jerome Arnold, president and chiefexecutive officer of Cibus. "It's the only therapy available todaythat has been shown (in a large study conducted by NIH) toreduce the mortality associated with elevated levels ofcholesterol."

GI licensed certain M-CSF patent and technology rights forNorth America to SciGenics (NASDAQ:SCGN) in May 1991.Schering-Plough holds the exclusive license from GI for M-CSFin Europe, Africa and South America. And Morinaga MilkIndustry Co. Ltd. is GI's licensee in Japan for M-CSF. ChironCorp. (NASDAQ:CHIR) of Emeryville, Calif., is also developing M-CSF, which it inherited from Cetus Corp. in their 1991 merger,for treating fungal infections in cancer and bone marrowtransplant patients. GI and Cetus cross-licensed eachother'spatents to M-CSF.

-- Jennifer Van Brunt Senior Editor

(c) 1997 American Health Consultants. All rights reserved.