By Aaron Lorenzo

Positive data presented Wednesday at the American Heart Association¿s Scientific Sessions 2001 conference gave CV Therapeutics Inc. a direct path to submit a new drug application for the anti-anginal drug candidate ranolazine to the FDA.

The company¿s Phase III CARISA (Combination Assessment of Ranolazine In Stable Angina) met its primary efficacy endpoint, showing ranolazine produced a statistically significant (p=0.012) increase in patients¿ symptom-limited exercise duration compared to placebo.

¿We¿re very excited,¿ CV Therapeutics Chairman and CEO Louis Lange said. ¿We will file the NDA within the next year.¿

More specifically, the company plans its submission during the third or fourth quarter of next year, Lange added.

Ranolazine is one of a new class of drugs called pFOX (partial fatty acid oxidation) inhibitors to treat chronic angina. The pFOX inhibitors could become the first new class of drugs to treat the condition in more than 20 years in the U.S.

The company will seek labeling indicating ranolazine use on its own or in combination with current anti-anginals, based on studies of the drug in both situations.

¿The results today open a broader part of the market for ranolazine,¿ Lange said. ¿This is the first new class of drugs to come along in a couple of decades to treat stable angina. This will help the 6.4 million Americans with angina who haven¿t had a new drug in over 25 years.¿

¿Clearly, the drug is approvable,¿ Dennis Harp, an analyst for Deutsche Banc Alex. Brown Inc., said. ¿The company has a potential blockbuster drug, and a great pipeline of additional products all focused on cardiovascular disease. The results of this study will put CV Therapeutics on the map. Ranolazine is poised to become the new standard of care.¿

From a business standpoint, the company began preparing for this day some time ago.

CV Therapeutics, of Palo Alto, Calif., put a marketing plan in place in May 1999 with Innovex Inc., a subsidiary of Research Triangle Park, N.C.-based Quintiles Transnational Corp. Quintiles made a $5 million investment when the deal was signed, and would pay $10 million when the product is launched. Innovex will launch and market the drug in the U.S. on a performance basis not to exceed 33 percent of revenues. Third- through fifth-year compensation to Innovex would be expected to equal 25 percent to 30 percent of total revenues.

CV Therapeutics would retain all product rights and books all revenues. It also has the final say on all strategic issues related to sales of the product and has the option after five years to convert the Innovex sales force to its own. (See BioWorld Today, May 12, 1999.)

¿It¿s a great way for a small company to shift some risk to someone else while we grow,¿ Lange said.

With the business of marketing out of the way, CV Therapeutics focused on its trials.

The 823-patient CARISA study was a multinational, randomized, double-blind, placebo-controlled, parallel-group trial. Over a 12-week period, patients received one of three background therapies (atenolol 50 mg, diltiazem CD 180 mg or amlodipine 5 mg) and were randomized to twice-daily doses of ranolazine 750 mg, ranolazine 1,000 mg, or placebo. Treadmill exercise testing was performed at trough, or lowest, plasma concentrations (12 hours after dosing) after two, six and 12 weeks, and at peak plasma concentrations (four hours after dosing) after two and 12 weeks. The endpoint was symptom-limited exercise duration at trough for all ranolazine patients compared to placebo at 12 weeks.

In both ranolazine dose groups combined, symptom-limited exercise duration at trough plasma concentrations increased on ranolazine by an average of 116 seconds, compared to an average increase of 92 seconds on placebo (p=0.012). The average increases on each ranolazine dose were 115 seconds on 750 mg and 116 seconds on 1,000 mg, compared to 92 seconds on placebo (p<0.03). The increases in exercise times on ranolazine were not significantly different among the three background therapies; insignificantly greater increases were seen over diltiazem and amlodipine than over atenolol.

The new data are similar to results of CV Therapeutics¿ prior Phase III trial of the drug from a study called MARISA (Monotherapy Assessment of Ranolazine In Stable Angina). That trial was a randomized, double-blind, placebo-controlled study of ranolazine in patients not receiving any other anti-anginal drugs. Its primary endpoint was the same symptom-limited exercise duration.

The company in January suffered a setback on news that CARISA needed an additional enrollment of 186 patients following a blinded interim assessment. That announcement resulted in a one-day stock drop of 35 percent. (See BioWorld Today, Jan. 8, 2001.)

The company¿s stock (NASDAQ:CVTX) gained $9.96 Wednesday, or 26 percent, to close at $48.35.

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