CV Therapeutics announced Friday that its cholesterol-loweringdrug CVT-1 has entered a Phase I safety trial in healthyvolunteers.

The orally active compound, a sulfated polysaccharide, has aunique mechanism of action. It blocks the transport proteininvolved in promoting the absorption of cholesterol intointestinal cells. CV Therapeutics' co-founders -- Louis Lange,chairman and chief executive officer, and Curtis Spilburg,executive director of development -- discovered thatcholesterol absorption is protein-mediated. They beganstudying CVT-1 while working at the University of Washingtonin St. Louis.

"Preclinical studies of CVT-1 have shown a 50 percentreduction in serum cholesterol in cholesterol-fed animals and a32 percent reduction in serum cholesterol in animals receivingnormal feed," CV Therapeutics of Mountain View, Calif.,reported.

Debra Bannister, CV Therapeutics' director of public affairs,said that unlike Merck & Co.'s Mevacor (lovastatin), an HMGCoA reductase inhibitor that works in the liver and has liver-associated toxicities, CVT-1 works in the intestine. She said thebile salt resins, another class of cholesterol-lowering drugs thatwork in the intestine, have to be taken in large quantities toabsorb cholesterol and have unpleasant side effects such asconstipation and bloating.

CVT-1 is CV Therapeutics' lead compound. Founded in 1992,the company is also in early-stage development of a syntheticinhibitor of macrophages. Bannister said one of the founders ofthe company discovered an anti-inflammatory compound thatblocks macrophage infiltration into injured tissue. She notedthat CV Therapeutics has synthesized a number of inhibitorsand expects to select a lead compound this year. Clinical trialsare projected for 1996.

The company is also collaborating with Genta Inc. to developand commercialize antisense drugs for prevention andtreatment of restenosis. A compound is in preclinicals and isexpected to enter clinicals next year.

-- Brenda Sandburg News Editor

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