Cardiologist Daniel C. Fisher has been trained by biotech CV Therapeutics to give speeches about its little-known heart drug Ranexa, and he believes the pill, meant to treat chest pain, could be a breakthrough. But he rarely prescribes it because of lingering safety concerns that prevent Ranexa, which aims to directly affect the muscle cells in the heart, from being used in all but the sickest patients.
Now CV Therapeutics is hoping that results from a big, Harvard-conducted study, due any day, could work magic on Ranexa sales. The study, called Merlin, is scheduled to be presented at a meeting of the American College of Cardiology in March, but some results could come far sooner via press release. The 6,500-patient study aims to prove that the drug can prevent heart attack, death or chest pain. But even if the study fails, it could allay safety worries and dramatically expand the number of patients who can get the drug.
Safety concerns are "the main thing" preventing physicians from writing lots of Ranexa prescriptions, says Fisher, who practices at New York University Medical Center.
The Food and Drug Administration approved the pill last January, making it the first new medicine cleared in two decades to treat the crushing chest pain caused by angina, a condition in which constricted blood vessels starve the heart muscle. But the FDA, worried about data showing that Ranexa caused changes in the heart's electrical rhythms that might lead to fatal arrythmias, restricted its use to those patients who are not helped by other medicines. "If Merlin shows there's no significant increase in arrythmias," Fisher says, "I'll feel more secure about the safety of Ranexa."
How big is the upside? Six million Americans have angina, but only 30,000 have been prescribed Ranexa. CV Therapeutics says that under an agreement with the FDA, clean safety data from Merlin would remove a restriction on Ranexa's packaging that instructs doctors to prescribe it only for patients who are not helped by other medicines. George B. Zavoico, who covers biotech stocks at Cantor Fitzgerald, estimates that the removal of this restriction could boost Ranexa sales to $140 million in 2007, from $17 million this year. He recently started coverage of CV Therapeutics (known also as CVT) with a "buy" rating.
Chief Executive Louis Lange, a cardiologist, co-founded CVT in 1990, when he was a professor at Washington University School of Medicine. He became the company's chief executive in 1992, hoping that new advances in biology and genetic science could lead to a new generation of heart drugs. In 1996, CVT licensed Ranexa from drug giant Roche Holding, which had acquired the company that had invented the medicine a decade before.
Patients with angina had plenty of treatments, but Ranexa promised to work in a new way. Existing treatments aim to increase blood flow to the heart. Nitroglycerin opens closed-up arteries; ACE inhibitors and calcium channel blockers lower blood pressure; and statins like Pfizer's Lipitor keep plaque from caking in the arteries. Heart stents mechanically open up arteries, improving blood flow. It's not known how the drug works, but Ranexa appears to protect heart cells when they are starved of blood.
Two big clinical trials appeared to show that Ranexa helped patients perform better on an exercise stress test, and CVT filed for FDA approval in 2002. But regulators were worried, because Ranexa caused an irregular reading on an electrocardiogram, called a lengthened QT interval; this is thought to be a risk factor for arrhythmia.
The FDA convened an advisory panel to analyze the drug, but it did not ask the panel to vote. At least one panelist said later that he would have voted to approve Ranexa then. (See: " A Biotech's Big Comeback.")
In 2004, CVT agreed to conduct two more big tests of Ranexa. The first of these studies finished in April 2005 and led to the approval of the drug for patients who aren't helped by other medicines. Merlin is the second study and will test to see whether Ranexa can actually save lives and reduce the need to treat angina with drugs, hospitalizations or medical procedures in patients who are at very high risk of heart attacks.
Fisher--and many on Wall Street--are skeptical that Ranexa can pull that off. Cantor Fitzgerald estimates that if Merlin is positive and Ranexa does not cause arrhythmias, CVT will book an extra $100 million in sales next year, and that Ranexa sales could top $600 million in 2010. Controversy over drug-coated stents, which are used to treat angina, and whether more patients should be treated with medicine, not stents, could also help Ranexa.
Lange says that he hopes to build his company into a biotech heavyweight
like Gilead Sciences or Genentech. He has a few other
potential hits, including a cardiac imaging drug and a treatment for atrial
fibrillation. But much of the hope for his company will be on the line when
the Merlin results are released, and when the full study is presented on
March 27 in New Orleans.