The US Food and Drug Administration (FDA) has granted approval for Amgen's Corlanor (ivabradine), an oral medication indicated to reduce the risk of hospitalization for worsening heart failure in patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction (LVEF) =35 per cent, who are in sinus rhythm with resting heart rate =70 beats per minute (bpm) and either are on maximally tolerated doses of beta blockers or have a contraindication to beta blocker use.

Heart failure is a common condition that affects approximately 5.7 million people in the US, about half of which have reduced left ventricular function. Despite broad use of standard treatments, the prognosis for patients with heart failure is poor. Projections show that by 2030, the prevalence of heart failure will increase 46 percent from 2012 estimates.

"We are excited to introduce Corlanor, the first new chronic heart failure medicine approved by the FDA in nearly a decade, for patients who are at a significantly greater risk of hospitalization due to worsening heart failure in the US," said Sean E. Harper, M.D., executive vice president of research and development at Amgen. "Many heart failure patients are repeatedly admitted to the hospital, which can cause a great burden on the patient and on healthcare resources. We hope that today's approval of Corlanor as an innovative therapeutic option will address a major unmet need for patients, their families and the healthcare system."

Heart failure costs an estimated $31 billion in the US each year, with the majority of the cost related to hospitalizations. By 2030, the cost of heart failure in the US is expected to increase almost 127 per cent totaling $70 billion.

"The approval of Corlanor is an important step forward for the treatment of patients with chronic heart failure in the US Because its mechanism of action is unique, it will complement the use of standard heart failure therapies, including beta blockers," said Jeffrey S. Borer, M.D., professor of Medicine, Cell Biology, Radiology and Surgery, and chief of Cardiovascular Medicine at State University of New York, Downstate Medical Center. "Despite beta blockade and other therapies, many people with chronic heart failure continue to suffer hospitalizations due to worsening heart failure. For these patients, when heart rate is greater than or equal to 70 bpm, Corlanor may be an appropriate treatment option and can be expected to add benefit."

Corlanor blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel responsible for the cardiac pacemaker, which regulates heart rate. Corlanor reduces the spontaneous pacemaker activity of the cardiac sinus node by selectively inhibiting the If current ("funny" current) to slow the heart rate with no effect on ventricular repolarization and no effects on myocardial contractility.

The Corlanor approval is based on global clinical trial data including a large, multicenter, randomized, double-blind, placebo-controlled, outcomes trial. The phase 3 SHIFT (Systolic Heart failure treatment with the If inhibitor ivabradine Trial) study compared Corlanor to placebo on top of standard of care (SOC) therapies, including beta blockers, in more than 6,500 clinically stable (=4 weeks) patients in sinus rhythm with reduced left ventricular function (LVEF =35 per cent) and heart rate =70 bpm, with a hospitalization for heart failure within the past 12 months. Patients received SOC, including beta blockers (89 per cent), angiotensin converting enzyme (ACE) inhibitors and/or angiotensin II receptor blockers (ARB) (91 per cent), diuretics (83 per cent) and anti-aldosterone agents (60 per cent).

Results from the phase 3 SHIFT study showed Corlanor significantly reduced the risk of the primary composite endpoint of hospitalization or cardiovascular death for worsening heart failure, with 18 per cent relative risk reduction (RRR) (p<0.0001, 4.2 per cent absolute risk reduction [ARR]) versus placebo. The treatment effect reflected only a reduction in the risk of hospitalization for worsening heart failure; there was no favourable effect on the mortality component of the primary endpoint. There was a 26 per cent RRR (4.7 per cent ARR) in the risk of hospitalizations for worsening heart failure.

The most common adverse drug reactions in the SHIFT study occurring in =1 per cent of patients on Corlanor compared to placebo were bradycardia (10 per cent vs. 2.2 per cent), hypertension or increased blood pressure (8.9 per cent vs. 7.8 per cent), atrial fibrillation (8.3 per cent vs. 6.6 per cent), and luminous phenomena (phosphenes) or visual brightness (2.8 per cent vs. 0.5 per cent).

Corlanor is expected to be available to patients in approximately one week.

Corlanor blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel responsible for the cardiac pacemaker, which regulates heart rate. Corlanor reduces the spontaneous pacemaker activity of the cardiac sinus node by selectively inhibiting the If current ("funny" current) to slow the heart rate with no effect on ventricular repolarization and no effects on myocardial contractility. Corlanor was developed by Les Laboratoires Servier. Through a collaboration with Servier, Amgen has rights to commercialize Corlanor in the US.

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