FDA Approves Amgen's Repatha for Prevention of Heart Attack and Stroke

December 1, 2017—Amgen announced that after priority review of its supplemental Biologics License Application, the US Food and Drug Administration (FDA) approved Repatha (evolocumab), the company's proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor to prevent heart attack, stroke, and coronary revascularization in adults with established cardiovascular disease.

In the United States, the indication for use for Repatha includes:

• Reducing the risk of myocardial infarction, stroke, and coronary revascularization in adults with established cardiovascular disease
• As an adjunct to diet, alone, or in combination with other lipid-lowering therapies (eg, statins, ezetimibe) for treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce low-density lipoprotein cholesterol (LDL-C)
• As an adjunct to diet and other LDL‑lowering therapies (eg, statins, ezetimibe, LDL apheresis) in patients with homozygous familial hypercholesterolemia who require additional lowering of LDL‑C

According to the company, in the 27,564-patient FOURIER cardiovascular outcomes study, Repatha reduced the risk of heart attack by 27%, the risk of stroke by 21%, and the risk of coronary revascularization by 22%.

The FOURIER study demonstrated that adding Repatha to optimized statin therapy resulted in a statistically significant 20% (P < .001) reduction in major adverse cardiovascular events represented in the key secondary composite endpoint of time to first heart attack, stroke, or cardiovascular death. The study found a statistically significant 15% reduction (P < .001) in the risk of the primary composite endpoint, which included hospitalization for unstable angina, coronary revascularization, heart attack, stroke, or cardiovascular death. The magnitude of risk reduction in both the primary and key secondary composite endpoints grew over time, with the robust benefit starting as early as 6 months and accruing through the median 2.2 years of the study.

Patients on Repatha experienced a reduction in the risk of heart attack (27%; nominal P < .001), stroke (21%; nominal P = .01), and coronary revascularization (22%; nominal P < .001). Consistent with recent trials of more intensive LDL-C lowering, there was no observed effect on cardiovascular mortality. Similarly, there was no observed effect on hospitalization for unstable angina.

The company noted that the safety profile of Repatha in the outcomes trial was generally consistent with the safety profile for the 12- and 52-week controlled trials involving patients with primary hyperlipidemia, including heterozygous familial hypercholesterolemia. Common adverse reactions included diabetes mellitus, nasopharyngitis, and upper respiratory tract infection.

Repatha is approved in more than 50 countries, including the United States, Japan, Canada, and in all 28 countries that are members of the European Union, advised Amgen.