Washington Editor

Promising Phase III data plus a respectable bank account prompted CV Therapeutics Inc. to renegotiate with partner Innovex Inc. for a return of all rights associated with the chronic angina candidate Ranexa.

In exchange for commercialization rights, including the opportunity to hire and train a sales force, CV Therapeutics has agreed to issue Innovex, a subsidiary of Research Triangle Park, N.C.-based Quintiles Transnational Corp., warrants for 200,000 shares at a price to be disclosed today. On Friday, CV Therapeutics' stock (NASDAQ:CVTX) closed at $35.37, up $2.32.

The companies had signed the original marketing and sales deal back in 1999 when things were a little different for CV Therapeutics. "We entered that deal before our Phase III trials were done and before the bull market," Louis Lange, chairman and CEO of Palo Alto, Calif.-based CV Therapeutics, told BioWorld Today. "We've been able to raise a fair amount of money. Our market cap then was $50 [million] to $60 million and we had approximately $39 million in cash. Today, our market cap is about a billion and we've got a little less than $500 million, so we are in a very different position today."

Innovex purchased $5 million in CV Therapeutics common stock in the original deal and was poised to receive a fee based on a percentage of sales in the first five years of Ranexa (ranolazine) sales and a royalty in the sixth and seventh years. (See BioWorld Today, May 12, 1999.)

Under the new terms, the companies will retain a commercialization services relationship and Innovex will become a preferred provider of pharmaceutical services for CV Therapeutics. Lange said the company has yet to file for regulatory approval outside the U.S. and has not determined whether it will seek partnerships overseas.

Analysts from Needham & Co. Inc. and Deutsche Bank-North America, both of New York, believe Ranexa will be approved later this year. Needham believes sales will reach $321 million by 2006 while Deutsche estimates the figure at $500 million.

If Ranexa is approved later this year, it would be CV Therapeutics' first product to market. The company is looking at hiring 100 to 200 sales reps, and already has hired Lewis Stuart to serve as vice president, sales.

Stuart has more than 20 years of sales and marketing experience, with prior employment at Agouron Pharmaceuticals Inc., of San Diego, and Bristol-Myers Squibb Co., of New York. He helped launch Agouron's Viracept, a protease inhibitor, and directed BMS's sales team for Capoten, an ACE inhibitor for high blood pressure and congestive heart failure, and Corgard, a beta blocker for angina and high blood pressure.

As for Ranexa, the FDA's Cardiovascular and Renal Drugs Advisory Committee will hear the case for the first-in-class candidate at the panel's Sept. 15-16 meeting. CV Therapeutics' Prescription Drug User Fee Act action date is Oct. 30.

CV Therapeutics submitted the Ranexa new drug application in December. Ranexa, which is in the class of partial fatty acid oxidation inhibitors, lets the heart burn glucose rather than fat for energy, thus lowering its demand for oxygen without reducing heart rate, blood pressure or pumping ability to stable, or chronic, angina, which is the regular pain associated with heart disease.

Among the data submitted as part of the NDA, CV Therapeutics included two successful pivotal Phase III trials called CARISA and MARISA. MARISA (Monotherapy Assessment of Ranolazine in Stable Angina) was a randomized, double-blind, placebo-controlled study of 191 patients not receiving any other anti-anginal products. Compared to placebo, Ranexa taken twice a day was statistically significant (p<0.005) in increased exercise duration at trough plasma concentrations, according to research notes released by Mark Monane, an analyst at Needham & Co. The CARISA trial (Combination Assessment of Ranolazine in Stable Angina) was a multinational, randomized, double-blind, placebo-controlled, parallel-group trial demonstrating that for patients on a background anti-anginal therapy, Ranexa significantly (p=0.012) increased symptom-limited exercise duration at trough drug concentrations compared to placebo. Furthermore, Monane said preclinical and clinical trials suggested that partial fatty acid oxidation inhibitors allow the heart to more efficiently use oxygen by shifting the heart's metabolism to consume glucose as a fuel source, which requires less oxygen to generate the same amount of energy.