Armed with positive data from two pivotal studies, CV Therapeutics Inc. filed a new drug application for regadenoson as a stress agent in myocardial perfusion imaging (MPI) tests.

The submission triggers a $7 million milestone from partner Astellas Pharma U.S. Inc., an affiliate of Tokyo-based Astellas Pharma Inc., which holds exclusive North American rights to commercialize the selective A2A-adenosine receptor agonist. Upon approval of regadenoson, expected in 2008, CVT stands to receive another $12 million milestone payment. Beyond that, CVT is eligible for "significant royalties" on product sales, said John Bluth, CVT's senior director of corporate communications and investor relations.

About 9.3 million patients in 2005 underwent MPI studies, which are used to detect and characterize coronary artery disease by identifying areas of poor blood flow in the heart. In many cases, that is performed in conjunction with an exercise treadmill test, but more than 45 percent of those patients aren't able to take the treadmill test due to medical conditions. Those patients require "a pharmacologic agent that can increase blood flow," mimicking the effects of exercise, Bluth said.

"Right now, Adenoscan is the market leader," he told BioWorld Today, referring to the adenosine injection marketed by Astellas, which, in prior years, has generated annual U.S. sales of more than $300 million. But that product has its drawbacks. Adenosine works by "stimulating all the adenosine receptors, so while it increases blood flow, it also invites some other activities," he said.

Adenoscan has been linked to serious side effects such as second- and third-degree atrioventricular block, cardiac arrest and ventricular tachycardia.

Regadenoson, on the other hand, is more selective, hitting only the A2A-adenosine receptor, which is responsible for coronary vasodilation. In two Phase III trials, the product met its primary endpoint by showing with 95 percent confidence that it is "essentially comparable" to Adenoscan in boosting the blood flow of patient undergoing MPI testing, "but with a profile that is more selective," Bluth said.

Another advantage is that regadenoson can be administered through rapid bolus without requiring any adjustments to the dose based on a patient's weight, which would make it more convenient than Adenoscan's adjusted doses given by infusion.

CVT partnered regadenoson with Fujisawa Pharmaceutical Co. Ltd., which later became Astellas, in 2000. Under the terms, CVT is responsible for managing the clinical development program, with Astellas taking over manufacturing, selling and marketing activities in North America. In addition to milestones and royalties, CVT also is reimbursed for 75 percent of the development costs. (See BioWorld Today, July 13, 2000.)

Outside North America, Palo Alto, Calif.-based CVT retains all rights to regadenoson, though it has not yet determined its strategy for overseas regulatory approval and commercialization. "We're still assessing those" options, Bluth said.

If regadenoson gains the FDA's blessing, it would become CVT's first "homegrown product" to reach the market, he added. Regadenoson "really was invented in the late 1990s, and it took less than a decade to get to an NDA."

It also would be CVT's second product approval in two years. The company introduced Ranexa (ranolazine extended-release tablets) early last year for the treatment as a second- and third-line use in chronic angina. Ranexa was licensed from an affiliate of Roche Holdings Ltd. in the mid-1990s. Sales of the angina product for the first quarter of 2007 totaled about $12 million.

CVT had hoped to broaden Ranexa's label to treat acute coronary syndrome, but reported in March that Ranexa missed its endpoint in a Phase III study. Results from that trial, however, are expected to enable the company to expand Ranexa's approval as a first-line angina treatment, and "we're looking to have that application submitted this fall," Bluth said. (See BioWorld Today, Jan. 31, 2006, and March 8, 2007.)

Elsewhere in its pipeline, CVT has CVT-6883, an oral, selective A2B-adenosine receptor antagonist that is in development for asthma and other pulmonary conditions. That product is in Phase I testing in asthma.

The company, which reported a net loss of $55.1 million, or 93 cents per share, for the first quarter, had a cash position of $267.1 million as of March 31.

Shares of CVT (NASDAQ:CVTX) fell 20 cents Tuesday to close at $9.51.

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