West Coast Editor

Building its bid for a larger share of the pulmonary arterial hypertension market, CoTherix Inc. licensed rights in North America and Europe from Asahi Kasei Pharma Corp. to develop and commercialize oral and inhaled fasudil, a rho-kinase inhibitor for PAH.

CoTherix, which also acquired exclusive rights to fasudil for stable angina in the same territories, will provide an up-front payment of $8.75 million to Tokyo-based Asahi, plus milestone payments and royalties on future products. The deal carries an option for CoTherix to develop fasudil in North America and Europe for other potential indications using the licensed formulations, with the exception of stroke and eye diseases.

An intravenous formulation of fasudil was approved in June 1995 in Japan, and Asahi markets the drug (through Eisai Co. Ltd., also of Tokyo) for prevention of cerebral vasospasm in patients with subarachnoid hemorrhage.

Various studies have shown that rho-kinase inhibitors reduce vasoconstriction and cell proliferation, and might be useful in PAH. The combined attack is "terrifically potent," said Donald Santel, CEO of South San Francisco-based CoTherix.

"There's nothing like [fasudil] in development," he told BioWorld Today. "This is why the doctors are glomming onto it. If you don't address the proliferation, we really can't talk about doing things that will meaningfully impact the disease progression."

Oral and intravenous fasudil were in-licensed by Schering AG in 2002, but Schering gave the drug back to Asahi two years later when the Berlin-based firm divested much of its cardiovascular portfolio.

"We approached Schering about [fasudil]," Santel said. "They said, 'We'd love to see you get it, just stay tuned,' and they made a very kind introduction to Asahi on our behalf. Their imprimatur helped us a great deal."

CoTherix plans to evaluate an extended-release, twice-daily formulation of fasudil and an inhaled version against PAH, with a pharmacokinetic study of fasudil ER in the second half of this year. An open-label, Phase IIa dose-ranging study with the ER version as a monotherapy in treatment-na ve patients is expected in the first half of 2007, possibly in Europe (since many patients already are being treated in the U.S.), although "we've not determined that yet," Santel said. "We are ambidextrous; we can do trials either place, and physicians [here] are quite enthusiastic."

In the first half of next year, the company aims to start a North American, Phase II dose-ranging trial of oral fasudil ER in stable angina, with a Phase II study testing inhaled fasudil against PAH in the second half.

Ventavis (iloprost) is CoTherix's inhaled prostacyclin, cleared for PAH in the U.S. at the end of 2004. Sales this year are expected to range between $60 million and $70 million. In the spring, the company increased the price by about 10 percent, putting the cost of a year's treatment at about $71,000.

The PAH zone recently has generated plenty of headlines. Earlier this month, Silver Spring, Md.-based United Therapeutics Corp. signed a licensing deal with specialty pharma firm Supernus Pharmaceuticals Inc., of Rockville, Md., for the ongoing development of UT-15C, the former's sustained-released prostacyclin analogue. (See BioWorld Today, June 14, 2006.)

The revenue leader in PAH is Tracleer (bosentan), Allschwil, Switzerland-based Actelion Ltd.'s endothelin agonist, cleared in Europe four years ago and approved in the U.S. in November 2001. Revatio, from New York-based Pfizer Inc., is a lower-dose form of sildenafil citrate (the active ingredient in the erectile-dysfunction drug Viagra), and was approved for PAH a year ago.

At the end of the first quarter, CoTherix had about $97.9 million in cash and equivalents. With the fasudil news, the firm said sales, general and administrative and research and development expenses in 2006 will total between $91 million and $98 million. At the end of the year, cash and cash equivalents and securities available for sale are expected to tally between $53 million and $63 million.

CoTherix's stock (NASDAQ:CTRX) closed Wednesday at $8.15, down 18 cents.