By Lisa Seachrist
Initial results from a Phase III study of CV Therapeutics Inc.'s ranolazine show the drug increased the amount of time patients with severe stable angina can spend on a treadmill.
The company's stock (NASDAQ:CVTX) soared on the news, jumping 56 percent to close at $13.812, up $4.937.
The early word from the trial testing 175 patients with severe stable angina, or chest pain caused by constricted blood flow to the heart, is that all three tested dosages increased the amount of time the patients could spend on an exercise treadmill compared to placebo. The final results will be presented at a scientific meeting late this year or early next year.
"These are very robust clinical results," said Louis Lange, chairman and CEO of the Palo Alto, Calif., company.
The data from the study called MARISA - Monotherapy Assessment of Ranolazine in Stable Angina - will be combined with that of the recently initiated CARISA, or Combination Assessment of Ranolazine in Stable Angina, in an effort to gain marketing approval from the FDA.
"We are looking for the broadest label possible," Lange said. "We expect to file in ."
Angina is the severe chest pain that occurs when obstructions in the coronary arteries deprive the heart of the oxygen it needs. Approximately 7.2 million Americans suffer from angina that can come on as a patient climbs the stairs or plays with a grandchild, Lange said. For some patients the pain is so severe that they will avoid the most basic activities of daily life.
Ranolazine is the first drug in a new class of therapies for angina called pFOX (partial fatty acid oxidation) inhibitors. Other therapies, such as nitrates, beta blockers and calcium channel blockers, work by slowing the heart rate and reducing the pumping force of the heart, leaving patients susceptible to congestive heart failure.
Ranolazine works by altering the metabolic balance of the heart, moving it away from dependence on oxygen-consuming fatty acid metabolism for energy and shifting it to glucose metabolism, which requires less oxygen. In effect, the drug lowers the oxygen demands of the heart while preserving the pumping capacity.
The MARISA study was a double-blind, placebo- controlled trial of the sustained-release formulation of ranolazine used in 175 patients who were receiving no other anti-anginal drugs. Compared to placebo, ranolazine, taken at doses of 500 milligrams, 1000 milligrams and 1500 milligrams twice a day, increased exercise duration on the treadmill. All of the measurements were conducted at the trough levels - or lowest blood concentrations - of the drug, approximately 11 hours after the last dose of the drug. Patients on the 500 milligram dose could remain on the treadmill 22 seconds longer than placebo patients; those on the 1000 milligram dose could stay on 35 seconds longer; and those on the 1500 milligram dose could stay on 49 seconds longer.
Lange pointed out the exercise treadmill test requires people to run on a 3 percent incline, which is extremely difficult for patients who ordinarily have difficulty walking half a block down the street.
"We frankly didn't expect the 500 milligram dose to be clinically effective," Lange said. "What this tells me is that the sustained-released form of the drug is much more effective than the immediate-release form."
The Phase II studies tested the immediate-release formulation. Lange said the company hadn't completed the analysis of the MARISA trial and didn't know the effect of the sustained-release form of the drug on heart rate and blood pressure. Phase II studies showed the immediate-release form of the drug didn't lower either heart rate or blood pressure.
The CARISA trial will study 750 milligram and 1000 milligram doses of ranolazine in combination with either a beta blocker or a calcium channel blocker.
In May, the company signed a marketing agreement with Innovex Inc., a subsidiary of Research Triangle Park, N.C.-based Quintiles Transnational Corp. The deal represented a new approach for marketing with CV Therapeutics basically outsourcing its marketing efforts.
Under the terms of the agreement Quintiles made a $5 million equity investment at market prices and agreed to pay $10 million upon product launch. Innovex will launch and market ranolazine in the U.S. on a performance basis that won't exceed 33 percent of revenues. The compensations to Innovex for years three to five is expected to equal 25 percent to 30 percent of total revenues (See BioWorld Today, May 12, 1999, p. 1.)
"Big pharma's investors have been reaping the rewards of the biotech investor," Lange said. "Because we get to keep so much of the profit of the drug, we are sort of rebalancing that."