2015年4月15日,美国食品和药品监管局(FDA)批准Corlanor(ivabradine)减低心衰恶化住院。
Corlanor被批准在其心脏左下部分收缩不好所致长期(慢性)心力衰竭某些人们使用。药物适用为患者有心力衰竭稳定，正常心跳有休息心率至少70跳/分症状和也服用可耐受的最高剂量β阻滞剂。
心力衰竭是一种常见情况在美国影响约5.1百万人。它是一种情况其心脏不能泵出符合机体需要血液。当心力衰竭随时间发展心脏泵动作变弱时。导致心力衰竭主要原因是损伤心脏疾病，例如冠心病和高血压。
FDA药物评价和研究中心心血管和肾产品室主任Norman Stockbridge，M.D.，Ph.D.说：“心力衰竭是成年人死亡和残疾的的主要原因，”“Corlanor被认为通过减低心率作用和代表在这个药物类别第一个被批准产品。”
Corlanor是在的优先审评程序下审评，这提供为加快审评药物是意向治疗某种严重疾病或情况和可能超过可得到治疗提供显著改善。它还被授予快速通道指定，它有助于促进发展和治疗严重或治危及生命情况和满足紧急医疗需求的药物加快审评。对于产品已被指定为快速通道产品，FDA可以滚动方式审评上市申请的部分。
在一项6,505例参加者临床试验研究Corlanor 的安全性和疗效。Corlanor与一种无活性药物(安慰剂)比较减短恶化心力衰竭至首次住院时间。
在临床试验参加者观察到最常见副作用是心率太慢(心动过缓)，高血压，房颤，和短暂视力障碍(光闪烁)。
Corlanor将与一个患者用药指南一起发放为其使用提供指导和重要药物安全性信息。卫生保健专业人员应与患者商讨关于药物对未出生婴儿危害风险，和用 Corlanor时不应成为妊娠。
患者如他们经受不规则心跳症状，感觉心脏是心怦怦跳或奔马[racing]，有胸部压迫感，或气短恶化应提醒卫生保健专业人员。低心率是Corlanor常见副作用和可能是严重。患者如他们有症状例如眩晕，虚弱或疲乏时应告诉他们的卫生保健专业人员。
Corlanor是总部在加州Thousand Oaks的Amgen公司制造。

FDA APPROVES CORLANOR® (IVABRADINE) TO REDUCE THE RISK OF HOSPITALIZATION FOR WORSENING HEART FAILURE IN PATIENTS WITH CHRONIC HEART FAILURE
THOUSAND OAKS, Calif. (April 15, 2015) – Amgen (NASDAQ:AMGN) today announced that the U.S. Food and Drug Administration (FDA) has granted approval of 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 percent, 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 U.S., about half of which have reduced left ventricular function.1,2 Despite broad use of standard treatments, the prognosis for patients with heart failure is poor.3 Projections show that by 2030, the prevalence of heart failure will increase 46 percent from 2012 estimates.1
“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 U.S.,” 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 U.S. each year, with the majority of the cost related to hospitalizations.4 By 2030, the cost of heart failure in the U.S. is expected to increase almost 127 percent totaling $70 billion.4
“The approval of Corlanor is an important step forward for the treatment of patients with chronic heart failure in the U.S. 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.5
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 percent) and heart rate ≥70 bpm, with a hospitalization for heart failure within the past 12 months. Patients received SOC, including beta blockers (89 percent), angiotensin converting enzyme (ACE) inhibitors and/or angiotensin II receptor blockers (ARB) (91 percent), diuretics (83 percent) and anti-aldosterone agents (60 percent).
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 percent relative risk reduction (RRR) (p <0.0001, 4.2 percent 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 favorable effect on the mortality component of the primary endpoint. There was a 26 percent RRR (4.7 percent ARR) in the risk of hospitalizations for worsening heart failure.
The most common adverse drug reactions in the SHIFT study occurring in ≥1 percent of patients on Corlanor compared to placebo were bradycardia (10 percent vs. 2.2 percent), hypertension or increased blood pressure (8.9 percent vs. 7.8 percent), atrial fibrillation (8.3 percent vs. 6.6 percent), and luminous phenomena (phosphenes) or visual brightness (2.8 percent vs. 0.5 percent).
The recommended starting dose of Corlanor is a 5 mg tablet twice daily with meals. After two weeks of treatment, the dose should be assessed and adjusted depending on heart rate. In patients with a history of conduction defects, or other patients in whom bradycardia could lead to hemodynamic compromise, initiate therapy at 2.5 mg twice daily before increasing the dose based on heart rate.
Corlanor is expected to be available to patients in approximately one week.
About Corlanor® (ivabradine)
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.5 Corlanor was developed by Les Laboratoires Servier. Through a collaboration with Servier, Amgen has rights to commercialize Corlanor in the U.S.
Important U.S. Product Information
Corlanor® is indicated to reduce the risk of hospitalization for worsening heart failure in patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction ≤ 35%, 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.
Important Safety Information
•Contraindications: Corlanor® is contraindicated in patients with acute decompensated heart failure, blood pressure < 90/50 mmHg, sick sinus syndrome, sinoatrial block, 3rd degree AV block (unless a functioning demand pacemaker is present), a resting heart rate < 60 bpm prior to treatment, severe hepatic impairment, pacemaker dependence (heart rate imposed exclusively by the pacemaker) and concomitant use of strong cytochrome P450 3A4 (CYP3A4) inhibitors.
•Fetal Toxicity: Corlanor® may cause fetal toxicity when administered to a pregnant woman.
•Atrial Fibrillation: Corlanor® increases the risk of atrial fibrillation. The rate of atrial fibrillation in patients treated with Corlanor® compared to placebo was 5% vs. 3.9% per patient-year, respectively.
•Bradycardia and Conduction Disturbances: Bradycardia, sinus arrest and heart block have occurred with Corlanor®. Concurrent use of verapamil or diltiazem also increases Corlanor® exposure and should be avoided. Avoid use of Corlanor® in patients with 2nd degree atrioventricular block unless a functioning demand pacemaker is present.
•Adverse Reactions: The most common adverse drug reactions in the SHIFT study occurring in ≥ 1% higher on Corlanor® than placebo were bradycardia (10% vs. 2.2%), hypertension or increased blood pressure (8.9% vs. 7.8%), atrial fibrillation (8.3% vs. 6.6%), and luminous phenomena (phosphenes) or visual brightness (2.8% vs. 0.5%).
Please contact Amgen Medinfo at 800-77-AMGEN (800-772-6436) regarding Corlanor availability or find out more information, including full Prescribing Information and Medication Guide, at www.amgen.com.