Call it a sad irony. Sanofi has discontinued a Phase IIIb trial in patients who were being treated with its Multaq heart med and suffer from permanent atrial fibrillation. Why? There was a significant increase in cardiovascular events. And so the study's operations committee and a data monitoring committee recommended ending the trial, known as Pallas.
This is only the latest setback for Sanofi and its Multaq heart med, which is supposed to bolster flagging fortunes. Last month, French regulators reevaluated the effectiveness of the drug after two patients developed severe liver damage and decided Multaq is “insufficient,” which means French authorities could withdraw reimbursement (see this). Sanofi says the decision to end the trial was not related to kidney damage (read here).
And last year, a study in the Journal of the American College of Cardiology found the pill is only modestly effective and has no clear safety benefits (see this) and more recently, questions were raised about the study in The New England Journal of Medicine that led to FDA approval (look here).
Multaq, by the way, is currently approved in the European Union in adult clinically stable patients with a history of, or current non-permanent Afib to prevent recurrence or lower ventricular rate. In the US, the pill is approved to reduce the risk of cardiovascular hospitalization in patients with persistent Afib or atrial flutter.
In explaining the decision, Sanofi says the patient population in the study was different from the population for which Multaq is approved. In the Pallas population, 70 percent of the 3,149 patients enrolled had permanent AF for over two years; approximately 70 percent had NYHA heart failure Class I to III at baseline. In contrast, in the study supporting the current indication, no patients enrolled had permanent AF and less than 30 percent had NYHA heart failure Class I to III. Pallas patients were also older than patients in the other trial, called Athena.
The Pallas trial was a multinational, randomized, double-blind, parallel-group, placebo-controlled, multicenter Phase IIIb trial comparing efficacy of 400mg Multaq taken twice-daily to placebo in permanent AF patients. They were required to be 65 years and older with co-morbid conditions, such as systemic arterial embolism, myocardial infarction, documented coronary artery disease, prior stroke, symptomatic heart failure, or the combination of age above 75 years, hypertension and diabetes mellitus.
heart attack pic thx to bart on flickr