By Kim Coghill
CV Therapeutics Inc.'s stock dropped 35 percent Friday after the company said it would enroll an additional 186 patients in a 462-patient Phase III study called CARISA (Combination Assessment of Ranolazine in Stable Angina), following a blinded interim assessment.
Meanwhile, the Palo Alto, Calif.-based company late Thursday filed shelf registration statements with the Securities and Exchange Commission to sell up to $400 million in debt securities, preferred and common stock and warrants.
Regarding the shelf registration, Louis Lange, CV Therapeutics' president and CEO, said, "It is purely opportunistic. If we are going to be a bigger company with the amount of cash we've got, then we want to have the flexibility to use it in a lot of different ways. We'd rather have it up and running so we can be quicker and more flexible."
The company has about $300 million in cash, he said. But addressing the company's plunging stock, Lange said, "You never really know why stock drops, but it looks like the investors took a dim view of our press release on the interim analysis."
CV Therapeutics' stock (NASDAQ:CVTX) Friday closed at $39.625, down $21.25.
The CARISA interim assessment was performed in order to minimize the risk of a false negative study. The interim evaluated the statistical variance of the primary endpoint - treadmill times - but did not assess the efficacy of ranolazine compared to placebo. Based on the variability in treadmill times, the protocol-specified interim analysis dictated enrollment of additional patients. The company expects to complete enrollment of the additional patients by the second quarter.
The CARISA trial is designed to examine the effectiveness of ranolazine in combination with other anti-anginal medications. Ranolazine is an investigational drug candidate in a new class of drugs known as pFOX (partial fatty acid oxidation) inhibitors.
"We originally planned to enroll 462 patients, and the study has been enrolling like a charm, and we actually would have hit our time line of finishing it by the end of the year in terms of enrollment," Lange said. "We picked 462 patients based on the standard deviation or how variable the measurement is of the endpoint - how long you can run on the treadmill. The bigger the standard deviation, the bigger the study is going to be."
Lange said testing was too optimistic and "with the money we've got, there's absolutely no reason not to add patients."
He said adding patients "is not bad news." However, "it didn't have a happy effect on trading, but in terms of the product, it actually increases the chance of a successful trial. This has to do with the statistics of the measurement, not whether the drug works."
In mid-November, CV Therapeutics released data on a subgroup analysis of a Phase III chronic angina trial for ranolazine, taken as monotherapy. It produced statistically significant (p<0.001) increases in exercise duration and time to angina pain compared to placebo in both younger and older patients with chronic angina. In a preclinical trial on ranolazine, results suggest it might increase the efficiency of the pumping action of the heart in dogs with experimentally produced congestive heart failure.
CV Therapeutics has another product, CVT-510, an A1 adenosine receptor agonist, in Phase II clinical trials for the treatment of atrial arrhythmias. CVT-3146, an A2A adenosine receptor agonist, is in Phase I clinical trials for the potential use as an adjunctive pharmacologic agent in cardiac perfusion imaging studies.