By Brady Huggett

Genentech Inc. grew its heart failure program by signing a potential $140 million development and co-promotion deal with the Swiss company Actelion Ltd., the second such deal between the two companies.

They will develop and co-promote Actelion¿s endothelin receptor antagonist, Tracleer, in the United States upon receiving marketing approval from the FDA. In February, Genentech signed a potential $75 million co-promotion deal for Actelion¿s heart failure drug, tezosentan.

¿With tezosentan and Tracleer, we will have potentially the first-to-market intravenous and oral endothelin receptor antagonists to address both acute and chronic cardiovascular diseases,¿ said Betsy Rosenberg, senior manager, corporate communications at Genentech. ¿We believe there are marketing synergies that exist between tezosentan and Tracleer and our other cardiovascular products.¿

The deal for Tracleer calls for an up-front $35 million payment this year from Genentech plus additional milestone payments that could make the total deal worth $140 million to Actelion, Rosenberg said.

The class of endothelin receptor antagonists as a whole is shaping up to be formidable, said Mark Augustine, an analyst at U.S. Bancorp Piper Jaffray in Minneapolis.

¿The receptors showed up well at the American Heart Association meeting in New Orleans,¿ he told BioWorld Today. ¿When we look at the class of drugs, they might have big sales, in the area of $500 million. They are very real candidates and have shown good efficacy. We should start to see them making contributions to the bottom line in 2002.¿

Augustine said the deal continues Genentech¿s work with the heart, and has some financial weight.

¿It¿s a sizable deal,¿ he said. ¿They have a U.S. profit split of 50-50. It takes advantage of Genentech¿s position in the cardiovascular area.¿

Both tezosentan and Tracleer work by blocking endothelin receptors. Endothelin is a naturally occurring protein that causes blood vessels to constrict. Abnormally high levels of endothelin have been found in cases of pulmonary hypertension and also acute and chronic heart failure. With tezosentan and Tracleer, Rosenberg said Genentech has products that relate.

¿The most important thing is that with the two agents, we will potentially have intravenous and oral doses to address both acute and chronic heart failure,¿ Rosenberg told BioWorld Today. ¿There are potential synergies between these products. These products complement each other.¿

Rosenberg said in the future tezosentan can be started in the hospital and Tracleer, with its oral dosing, will be something that can be administered at home.

Tracleer showed encouraging results compared to placebo in a pivotal Phase III trial for pulmonary hypertension, and Actelion used the data to submit a new drug application to the FDA on Nov. 22. The FDA agreed to accept a later submission of data from a larger Phase III trial, BREATHE-1 (Bosetan Randomized Trial of Endothelin Receptor Antagonist Therapy for Pulmonary Hypertension), that is expected to expand and confirm the earlier results, Rosenberg said.

Tracleer also is being evaluated in two pivotal Phase III trials, ENABLE-1 and ENABLE-2 (Endothelin Antagonist Bosetan for Lowering Cardiac Events in Heart Failure), involving more than 1,600 patients with coronary heart failure. ENABLE-1 is being conducted in Europe, Israel and Australia; ENABLE-2 in North America. The studies look at patients after nine months of treatment with Tracleer in combination with conventional therapy, and the trials are expected to be finished in the third quarter of 2001, Rosenberg said.

Actelion, of Allschwil, publicly traded on the Swiss Stock Exchange (SWX:ATLN), focuses on the endothelium ¿ the single layer of cells separating blood vessels from the bloodstream. It is conducting drug discovery programs in cardiovascular diseases, malaria, Alzheimer¿s disease and cancer.

Genentech, of South San Francisco, discovers, develops, manufactures and markets human pharmaceuticals for unmet medical needs.

Genentech¿s stock (NYSE:DNA) dropped $1.562 Wednesday to close at $78.875.