BioWorld International Correspondent

Swiss drug development firm Axovan AG is looking to move its lead compound clazosentan, for prevention of cerebral vasospasm following subarachnoid hemorrhage (SAH), into a Phase III clinical trial in the first quarter of 2004. That follows a positive multicenter Phase II clinical trial in Germany, which involved 34 patients.

The Allschwil-based company has not yet disclosed data from the double-blind, placebo-controlled, randomized study, but plans to do so soon in a scientific publication. "Some of the endpoints have been achieved with statistical significance," CEO and co-founder Olivier Valdenaire told BioWorld International.

Vasospasm occurs in about half of the 80,000 patients in Europe and the U.S. each year who are affected by SAH, a bleeding event in the brain associated with the rupture of an aneurysm. It consists of a spasm of blood vessels in the brain, which can lead to additional disability and death. Clazosentan is an antagonist of the endothelin A receptor, which, Valdenaire said, mediates the vasoconstrictive effects of endothelin 1, the most abundant of the family of 21-amino-acid peptides that elicit vasoconstrictor and pressor responses in different parts of the body.

The compound is administered by intravenous injection and can cross the blood-brain barrier without causing any apparent harm. "Something which is great about this compound is that there is no effect on the systemic blood pressure," Valdenaire said. Existing treatments for the condition include administration of the calcium channel blocker nimodipine; post-operative hypertensive-hypervolemic-hemodilution (triple H) therapy; and balloon angioplasty. But none of those is satisfactory as either a treatment or a preventive measure, according to Axovan.

It now is drawing up a protocol for the upcoming study, which could take place in either Europe or the U.S. The company has not yet sought orphan designation for the product. "That is something we are considering," said Valdenaire.

Axovan originally licensed clazosentan from F. Hoffmann-La Roche Ltd., of Basel, Switzerland, and its Japanese subsidiary Chugai, and they retain an option to reacquire the compound following a Phase III study. Axovan is planning to fund the Phase III trial from its own resources and intends to raise additional cash before the year-end.

The company, which was founded in 2000 by Valdenaire, head of R&D Thomas Giller and Allschwil-based Actelion Ltd., raised CHF38 million (US$27.8 million) in its first two financing rounds. Its main focus is on finding modulators of G protein-coupled receptors. "Our next product to enter the clinic should do so in the next 18 months," Valdenaire said. That compound is in development for thrombosis.