Washington Editor

CV Therapeutics Inc.'s stock fell 27.2 percent a day in advance of its appearance before an FDA panel to present its new drug application for Ranexa (ranolazine), a chronic angina candidate.

The company's stock (NASDAQ:CVTX) Monday closed at $12.21, down $4.55. As is customary, trading will be suspended during the hearing of the Cardiovascular and Renal Drugs Advisory Committee Tuesday in Gaithersburg, Md.

In a series of letters and review papers comprising the FDA's "briefing document" for the candidate, government reviewers questioned certain safety issues, but seemed to believe that Ranexa could be approved under certain conditions.

The agency believes Ranexa produces an anti-angina effect as evidenced by improvement in exercise tolerance at peak in the two pivotal trials. Also supportive is a decrease in anginal attacks and nitroglycerin consumption. However, the agency said there have been no studies related to outcomes and it isn't known whether or not ranolazine affects survival.

A major safety issue, the FDA said, is repolarization. In addition, since ranolazine is metabolized via the cytochrome pathway, the potential arises for drug interactions leading to increased concentration, it said. Other issues include exploration of dosing and dose-response, establishment of benefit in women and benefit risk.

Finally, the FDA raised a concern over potential testicular toxicity in rats that manifested as impaired fertility.

CV Therapeutics, of Palo Alto, Calif., submitted its NDA last December and received an approvable letter from the agency in October. The panel hearing originally was scheduled for September, but postponed until December, a decision that did not impact the FDA's requirement to issue action by the end of October. (See BioWorld Today, Dec. 31, 2002; Aug. 5, 2003; and Nov. 3, 2003.)