Glycomed Inc. said Wednesday that its drug Astenose reducedrestenosis by 50 to 75 percent in a study of baboons treatedwith the drug for 30 days.
The baboons received experimental injuries from balloonangioplasty and were then divided into three treatment groups.One group was given Astenose 24 mg/kg/day for seven days, asecond group got that dosage for 30 days, and a control groupreceived no drug. All the animals were examined 30 days afterarterial injury.
"Using the degree of restenosis (narrowing of the arteries)observed in the control group as a reference, animals receivingAstenose for 30 days showed statistically significant reductions(50-75 percent) in all parameters of restenosis in all vesselssubjected to experimental injury," Glycomed said.
Among baboons treated with the drug for seven days andexamined 23 days later, "the data suggested an increase in theinternal diameter of the vessels subjected to angioplasty," saidGlycomed. "This change may be of therapeutic importance if itcan be confirmed in human trials. However, the proliferativeresponse within the vessel walls was not significantlydecreased in the arteries."
Glycomed (NASDAQ:GLYC) said that in other safety studiesbaboons received seven or 28 days of continuous intravenousinfusions of Astenose at doses ranging from 5 to 100mg/kg/day; no dose-limiting systemic or organ toxicities wereobserved until doses of 45 or 100 mg/kg/day were given. Thecompany said these doses are two to 10 times the anticipatedhuman therapeutic dose.
The baboon study was conducted by researchers at EmoryUniversity in association with the Southwest Foundation forBiomedical Research. Glycomed's assistant vice president ofmedical affairs, Sam Teichman, told BioWorld that this is thefirst drug for restenosis to show efficacy in baboons, with theexception of high-dose fish oil (omega-3 fatty acids), which hasalso shown preliminary efficacy in humans.
Astenose is a form of heparin that has been chemicallymodified by a proprietary process so it has reduced anti-coagulant properties. Teichman said the drug seems to work byinhibiting smooth muscle cell growth and potentially byaffecting the vascular remodeling that occurs during thehealing process after balloon angioplasty.
He explained that balloon angioplasty stretches the artery andat the same time injures its lining. The lining regenerates, but"in some patients there is an overshoot of the healing processthat leads to re-narrowing of the artery."
Glycomed of Alameda, Calif., plans to file an investigational newdrug application for Astenose in the first quarter of 1994 fortreating vascular restenosis following angioplasty and plans tobegin Phase I testing in the second quarter.
Astenose was discovered by Glycomed just before the companyentered a three-year collaboration with Eli Lilly and Co. Underthe terms of the January 1990 agreement, Glycomed licensedrights to compounds for preventing restenosis andatherosclerosis, including Astenose, to Lilly for royaltypayments. Glycomed regained rights to Astenose about a yearago. Lilly is conducting preclinical tests of the drug for otherindications. If it decides to pursue clinical development for anyindication it will have to renegotiate with Glycomed for suchrights.
Several other companies have compounds in preclinicaldevelopment for treatment of restenosis. They include GentaInc., which is collaborating with CV Therapeutics Inc. and aStanford researcher to commercialize antisense drugs forprevention and treatment of restenosis; Prizm PharmaceuticalsInc.'s fibroblast growth factor; Seragen Inc.'s epidermal growthfactor receptor-targeted fusion toxin DAB389EGF; CorTherapeutics Inc.'s thrombin receptors; and NeoRx Corp.'s Bio-Flow.
-- Brenda Sandburg News Editor
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