Washington Editor

CV Therapeutics Inc. started a second Phase III study of regadenoson, a selective A2A-adenosine receptor agonist being developed for potential use as a pharmacologic stress agent in cardiac-perfusion imaging studies.

Regadenoson, also called CVT-3146, also is the subject of an earlier Phase III initiated in October by CV Therapeutics, of Palo Alto, Calif., and its partner, Fujisawa Healthcare Inc., a subsidiary of Fujisawa Pharmaceutical Co. Ltd., of Osaka, Japan. (See BioWorld Today, Oct. 30, 2003.)

John Bluth, CV Therapeutics' senior director of corporate communications, told BioWorld Today the partners are not releasing specific details related to the international, double-blind Phase III program.

While he wouldn't discuss an estimated timeline for completion, he said the partners' goal is to seek regulatory approval as soon as possible. CVT-3146 is meant to help patients undergoing a cardiac-perfusion imaging test who can't exercise sufficiently to generate the increase in coronary blood flow needed for the test. CVT-3146 is being studied to determine if it could temporarily increase the coronary blood flow to mimic what would be produced from exercise. In 2002, about 7.8 million U.S. patients underwent cardiac-perfusion imaging studies, CV Therapeutics said. More than 40 percent of patients undergoing those tests are unable to exercise adequately because of medical conditions, such as peripheral vascular disease, arthritis or other conditions that would prevent them from using a treadmill.

There are other stress agents available for the problem. In fact, Fujisawa markets one, called Adenoscan. The active ingredient in Adenoscan, adenosine, interacts with a variety of adenosine receptors, including A2A, which stimulates vasodilation and coronary blood flow so that cardiac-perfusion imaging studies can be done without exercise. But because adenosine acts on all of its receptors, not just A2A, it can cause side effects. Since regadenoson selectively stimulates the A2A adenosine receptor, the partners expect it could have fewer unwanted side effects, Bluth told BioWorld Today.

In previous trials, regadenoson has proved to be well tolerated with a few drug-related adverse events that included chest discomfort, increased heart rate, hypotension, flushing and shortness of breath, which were mild and self-limited, the companies said.

On entering the partnership for regadenoson, Fujisawa agreed to pay CV Therapeutics $34 million up front and potential milestones for exclusive North American rights to the candidate. Fujisawa also will fund 75 percent of development costs and would pay CV Therapeutics a double-digit royalty. CV Therapeutics retains all rights outside Fujisawa's territory. Bluth said the firm hasn't made any decisions on additional partnerships. (See BioWorld Today, July 13, 2000.)

CV Therapeutics received a $3 million milestone payment on initiating the first Phase III trial. Since signing the collaboration, CV Therapeutics has received $15 million (including the recent milestone) in payments, plus reimbursements for clinical development, and is poised to collect another $19 million in cash tied to other development and regulatory milestones.

Meanwhile, CV Therapeutics is in discussions with the FDA regarding the firm's lead candidate, Ranexa (ranolazine), a proposed treatment for chronic angina. The company believes it can get Ranexa to market by successfully completing an additional study. Indeed, the FDA in November issued a conditional approval letter on Ranexa, but sought additional clinical information. CV Therapeutics' stock slipped 21.7 percent, or $4.89, to close at $17.63 on the news. (See BioWorld Today, Nov. 3, 2003.)

In December, the Cardiovascular Renal Drugs Advisory Committee generally agreed that Ranexa would be approvable if CV Therapeutics completed another clinical trial in a population that would include patients who did not respond to maximal therapy. The panel did not take a formal vote on Ranexa.

Typically, advisory panels meet before the FDA issues a decision on a drug. But in this case, the agency and company mutually agreed to postpone the meeting from September to December. However, the FDA was compelled to act on the drug application on or before the firm's Prescription Drug User Fee Act date in accordance with federal law. (See BioWorld Today, Aug. 5, 2003.)

CV Therapeutics' stock (NASDAQ:CVTX) rose 60 cents Monday to close at $15.65.