Firming up an advisory panel's opinion in December, the FDA has agreed to a special protocol assessment (SPA) program for the next clinical trial of Ranexa, CV Therapeutics Inc.'s treatment for chronic angina.
The company's stock (NASDAQ:CVTX) rose $2.32 on the news, or 17.6 percent, closing Thursday at $15.53, after trading as high as $16.88.
"This really mitigates the regulatory uncertainty," said John Bluth, senior director of corporate communications at CV Therapeutics.
The FDA's SPA program "has been around for a few years now," he noted. "Some of them are for your first pivotal Phase III studies" - whereas CV Therapeutics already has completed two and gained an approvable letter from the FDA.
Although it didn't take a formal vote, the Cardiovascular Renal Drugs Advisory Committee in December generally agreed that Ranexa (ranolazine) would be approvable if CV Therapeutics completed another clinical trial in a population that would include patients who did not respond to maximal therapy. (See BioWorld Today, Dec. 10, 2003.)
Now, the company and the agency have a written agreement on a protocol for a trial, which, if successful, would support the approval of Ranexa in chronic angina in a restricted patient population. Enrollment is expected to begin in the third quarter, with at least one more trial planned later in the year to support marketing clearance in a broader patient population.
"We're going to make the most of the time we have here," Bluth told BioWorld Today, adding that the company hopes to complete enrollment in the trial by the end of 2005. Meanwhile, it is talking with the Thrombolysis in Myocardial Infarction research network about a broader-label trial, which likely would be in ischemic patients with acute coronary symptoms and angina, though nothing is decided yet, he said.
A partial fatty-acid oxidation inhibitor, Ranexa works by letting the heart use glucose rather than fat for energy, thereby lowering its demand for oxygen without reducing heart rate, blood pressure or pumping ability. The company owns all rights in the U.S. and Europe and intends to market the product itself in those areas for chronic angina.
The study agreed upon by way of the SPA program will be a multinational, double-blind, randomized, placebo-controlled, parallel-group study to test Ranexa's efficacy in about 500 patients with chronic angina who remain symptomatic despite daily treatment with the maximum labeled dose of amlodipine (10 mg daily), an approved calcium channel blocker.
Eligible patients will be randomized to get 1,000 mg of Ranexa or placebo twice daily plus a daily dose of 10 mg of amlodipine during a six-week assessment period. The primary efficacy endpoint of the study will be angina frequency.
Based on the reduction in angina frequency observed in an earlier Phase III CARISA study, the SPA study is 95 percent powered to detect a statistically significant reduction in angina frequency thanks to Ranexa, the company said. In CARISA, Ranexa at the 1,000-mg dose cut back angina frequency by an average of 1.2 attacks per week, compared to placebo (p<0.001).
Other goals of the new study will be to gather additional data on the safety and tolerability of Ranexa and to learn more about the drug's effect on nitroglycerin consumption during angina attacks, as well as quality of life.
Before they can enter the trial, patients will have had at least two weeks of treatment with amlodipine 10 mg daily, and must have discontinued other anti-anginal therapy for at least five days. They also must have documented evidence of coronary artery disease or prior myocardial infarction, plus the diagnosis of chronic angina.
"The important concept is, the single study is approval-enabling, and we're not stopping there," Bluth said. "We're interested in the broadest label possible."