April 16th, 2015
FDA Approves New Heart Failure Drug
The FDA on Wednesday approved ivabradine (Corlanor), Amgen’s new heart failure drug. The drug has been available for several years in Europe, where it is sold by Servier under the brand names of Corlentor and Procoralan.
Ivabradine was approved for the reduction of hospitalization from worsening heart failure. It is indicated for use in stable heart-failure patients who are in sinus rhythm, have a resting heart rate of at least 70 bpm, and who are also taking the highest tolerable dose of a beta blocker. Ivabradine slows the rate of the heart by inhibiting the so-called “funny” current within the heart’s natural pacemaker, the sinoatrial node. The drug received an expedited review under the FDA’s priority review program.
Approval was based on results of the SHIFT trial, published in 2010, which studied 6,558 patients with heart failure who had a heart rate > 70 bpm. After a median 22 months of followup, the rate of cardiovascular death or hospital admission for worsening heart failure was 24% in the ivabradine group and 29% in the placebo group (HR 0.82, 95% CI 0.75–0.90, p<0.0001).
The FDA said that that the most common side effects of the drug were bradycardia, hypertension, atrial fibrillation, and temporary vision disturbance (flashes of light). The FDA said that ivabradine can cause harm to fetuses and that women should not become pregnant while taking it.
In Europe ivabradine has been approved for use for both heart failure and stable angina. In 2014 results from a 19,000 patient stable-angina trial, SIGNIFY, prompted the European Medicines Agency (EMA) to make several recommendations intended to lower the risk of heart problems linked to the drug. Although the overall results of SIGNIFY were neutral, troubling findings occurred in the very large subgroup (more than 12,000 patients) with symptomatic angina. The EMA review concluded that in these patients ivabradine, compared with placebo, had a small but significant increase in the risk of CV death and nonfatal MI (3.4% vs. 2.9% yearly incidence rates) and a substantially higher risk of bradycardia (17.9% vs. 2.1%). The EMA said ivabradine was also associated with an increased risk for atrial fibrillation. SIGNIFY tested a higher dose of ivabradine, but the EMA concluded that the high dose “did not fully explain the findings.”