HAMBURG, Germany - The German biopharmaceutical product company MediGene AG, of Martinsried near Munich, has in-licensed the drug Etomoxir to treat congestive heart failure (CHF). The new lead compound in MediGene's cardiac disease area has already finished Phase I clinical trials successfully.

Using a proprietary heart EST database, MediGene has identified a couple of candidate genes responsible for the early onset of cardiomyopathies and reported the validation of a novel target involved in the development of CHF earlier this year (see BioWorld International, June 9, 1999). "We combine disease-focused target discovery with target analysis and validation in vitro and in vivo," Peter Heinrich, CEO of MediGene, told BioWorld International, "and very early our results indicated that the oxidation of fatty acids is pathologically increased in patients with congestive heart failure. The novel drug fits to a group of targets involved in this process."

Etomoxir, a compound with a molecular weight of 320, is a selective inhibitor of a mitochondrial key enzyme that oxidizes long chain fatty acids. Hence the uptake of fatty acids in the mitochondria is blocked and the cell meta bolism switches from fatty acid to glucose oxidation, a more efficient form of energy supply in the diseased heart.

"Originally, Etomoxir had been developed by Byk Gulden, of Konstanz, Germany, as a compound for the treatment of diabetes as the increase in glucose oxidation lowers the blood glucose level," Heinrich said. But the development was given up by Byk Gulden after Phase I and Phase II clinical trials involving more than 200 diabetes patients proved that the compound was not more efficient than existing anti-diabetes drugs. "However, in the clinical trials it was noticed that Etomoxir showed a favorable effect on the heart."

Nevertheless Byk Gulden decided to hand back the rights and patents to the inventor, since heart disease treatment was outside the company's portfolio. "We obtained a license and now hold the full rights to the compound, covering both substance and indication. Besides, patents on back-up compounds for this indication and extensions of the use to other cardiac diseases are included," Heinrich said.

Phase II clinical trials are scheduled to start in March next year with more than 200 patients. He said the company is "very enthusiastic about the therapeutic prospects: Phase Ib studies in patients suffering from congestive heart failure showed very promising results, and besides, the studies indicate a good safety profile. So we believe it has a very good potential to tackle the deregulation of heart metabolism in CHF patients, and as about 8.5 million patients in Europe and the U.S. suffer from this disease, we see an excellent market opportunity. It is a perfect and sound strategic addition to our product pipeline."

Heinrich added that MediGene would develop additional targets and compounds in its cardiology pipeline. "We will further concentrate our efforts on product development, and this new lead compound encourages us very much on our way. We are committed to go public next year, and we will soon announce a new and major collaboration."