Ranexa, CV Therapeutics Inc.'s drug for angina, generated positive data in a Phase III study that positions the product one step closer to the market.
The company said Ranexa (ranolazine) met the primary endpoint of reducing weekly angina frequency compared to placebo (p=0.028). The 565-patient study, labeled ERICA (Evaluation of Ranolazine In Chronic Angina), was conducted under the FDA's special protocol assessment process, meaning the findings could support approval for chronic angina in a restricted patient population, following an approvable letter issued a year and a half ago. An amendment to Ranexa's original new drug application is expected to be filed by the end of next quarter.
"These results are a big win for patients, physicians and the company," John Bluth, the company's senior director of corporate communications, told BioWorld Today. "The study clears the path to approval, we believe."
That sentiment was echoed in the investment community by Caroline Stewart, a senior analyst at IRG Research Inc. in New York. She told BioWorld Today that there was "no question" that the ERICA data satisfy the approvable letter, though she acknowledged that naysayers fear there to be too many competitive market penetration hurdles.
The approvable letter was followed by a meeting during which the FDA's Cardiovascular Renal Drugs Advisory Committee said the drug would be approvable if CV Therapeutics completed another trial with patients who did not respond to maximal therapy. (See BioWorld Today, Dec. 10, 2003.)
The latest findings demonstrated success in that regard. Data showed that from a baseline of 5.5 weekly angina episodes, Ranexa therapy reduced that figure to 2.8, while placebo treatment lowered it to 3.2. Also, a quarter of Ranexa patients had fewer than 1.2 episodes a week. The trial evaluated Ranexa's effectiveness when dosed at 1,000 mg twice daily in patients who had more than three angina attacks per week despite daily treatment with the maximum labeled dose of the calcium channel blocker amlodipine, 10 mg daily. There was a six-week assessment period, at the start of which long-acting nitrates were allowed as background therapy. (See BioWorld Today, June 4, 2004.)
"This was a very well-treated patient population," Bluth said, "a group that was on the maximum labeled dose of an anti-anginal therapy, and despite being on that therapy, they still saw an additional benefit from Ranexa. And not only were they on 10 mg of amlodipine, but about half the patients were also on long-acting nitrates. It makes the statistically significant result very relevant to the potential benefit-risk profile for Ranexa."
The drug was well tolerated, and there were no cases of syncope, which includes episodes of fainting or lightheadedness. CV Therapeutics is withholding more specific results, as it plans to present them at a future scientific conference. Secondary objectives in the study were to gather additional data on Ranexa's safety and tolerability, and to learn more about its effect on nitroglycerin consumption during angina attacks and quality of life.
The Palo Alto, Calif.-based company expects to prepare the final study report, integrate the data from ERICA into an existing safety and efficacy database and soon submit an amendment to the NDA. Once done, a best-case scenario would envision a six-month review, approval and launch in the first half of next year. The drug already is under regulatory review in Europe.
"If Ranexa is approved, it would represent the first new class of anti-anginal therapy approved in the U.S. in more than 25 years," Bluth said, noting that existing treatments work by reducing heart rate or blood pressure while Ranexa does not appear to have a clinically significant impact on either. "So that prospect is very exciting for patients."
Stewart said Ranexa's mechanism clearly differentiates it from available beta-blockers and calcium channel blockers.
"It doesn't make your angina go away, but neither do these other drugs," she said. "And it has a different mechanism of action."
Chronic angina, a condition typically associated with coronary artery disease and marked by repeated and sometimes unpredictable chest pain, affects about 6.4 million people in the U.S., according to the American Heart Association. Bluth said an approval based on the latest data would allow the drug to be prescribed for about 10 percent to 25 percent of that total market.
Two earlier Phase III studies, CARISA and MARISA, formed the basis of the original NDA for Ranexa. Another Phase III trial, called MERLIN, is under way to evaluate the drug's safety and efficacy during acute and long-term treatment in about 5,500 patients with non-ST elevation acute coronary syndromes treated with standard therapy. Should that latter trial prove successful, it could open the door for a broad approval of the drug. Bluth, who said the safety data alone could lead to a broader indication, added that the study data could be available by the end of next year. (See BioWorld Today, Aug. 2, 2004.)
Banking on an earlier approval, CV Therapeutics is in the process of establishing a sales force that initially will be involved with a partnered product, Aceon (perindopril), and eventually would be leveraged for Ranexa. Aceon, the subject of an agreement with Solvay Pharmaceuticals Inc., of Marietta, Ga., is under FDA review for a label expansion and should that get approved per its PDUFA date in the next two months, it would effectively be re-launched in part with CV Therapeutics' sales force. Subsequently, that team would lay the groundwork for Ranexa sales.
"If you consider Aceon a re-launch," Bluth said, "CV has the opportunity to launch two cardiovascular products within the next 12 to 16 months."
By the end of this year, the company expects to report Phase III data from two studies of regadenoson, a selective A2A-adenosine receptor agonist, for potential use as a pharmacologic stress agent in myocardial perfusion imaging studies. Tecadenoson, a selective A1-adenosine receptor agonist for the potential reduction of rapid heart rate during atrial arrhythmias, also is in Phase III. Lastly, Adentri is a selective A1-adenosine receptor antagonist for the potential treatment of heart failure. Licensed to Biogen Idec Inc., of Cambridge, Mass., it has completed Phase II.
On Monday, CV Therapeutics' shares (NASDAQ:CVTX) gained 2 cents to close at $20.75, although the stock traded nearly 10 percent higher earlier in the day.