Ivabradine, a heart rate-reducing drug from Servier and Amgen ($AMGN), failed to beat placebo in a huge study of patients with coronary artery disease, potentially clouding its future on two continents.
Servier, which markets the drug in Europe for stable chest pain and chronic heart failure, had planned to demonstrate that its cardiac-current inhibitor could improve outcomes for patients with CAD by reducing their mean heart rates. However, in results from a 19,000-patient study published in The New England Journal of Medicine this week, the drug missed its primary endpoint of reducing the rate of cardiovascular death in patients with CAD and, even worse, significantly increased such risks in a large patient subgroup.
Meanwhile, Amgen is toiling away on the drug in the U.S. after paying $50 million up front for its stateside rights last year. Amgen's lead indication is chronic heart failure, for which it received the FDA's priority review designation last month, and the Big Biotech has made no mention of the drug's CAD potential since first announcing the deal. The company expects a final agency decision on its application in the next 6 months.
Whether ivabradine's European scrutiny will affect Amgen's ambitions remains to be seen, but the CAD flop could well imperil Servier. The European Medicines Agency is in the midst of a safety review of ivabradine, sold as Procoralan overseas, weighing whether to maintain its approval of the drug.
In the three-month study, dubbed SIGNIFY, ivabradine did its job in lowering patient heart rates by about 10 beats per minute on average but resulted in no significant difference between the treatment and placebo groups in rates of cardiac death--6.8% to 6.4%. Furthermore, among the roughly 12,000 patients with activity-limiting chest pain, the ivabradine group clocked a 7.6% rate compared to 6.5% for those on placebo, a statistically significant margin.
In an editorial accompanying the study, NEJM editors warn that doctors should be "very cautious in interpreting subgroup results" but add that they should take extra care in deciding whether to prescribe the drug for patients with severe angina.
- read the results
- here's the editorial