FDA Approves Repatha to Prevent Heart Attack and Stroke

Evolocumab is the first PCSK9 Inhibitor to win this indication

Evolocumab (Repatha, Amgen) has become the first PCSK9 inhibitor approved by the FDA to prevent heart attacks, strokes, and coronary revascularizations in adults with established cardiovascular disease.

The FDA also approved evolocumab to be used as an adjunct to diet, alone or in combination with other lipid-lowering therapies, such as statins, for the treatment of adults with primary hyperlipidemia to reduce low-density lipoprotein-cholesterol (LDL-C).

"Despite treatment with current best therapy, many patients are still at high risk for cardiovascular events. Physicians now have a new FDA-approved treatment option to prevent cardiovascular events by dramatically lowering LDL cholesterol with Repatha, especially for patients already on maximally-tolerated statin therapy who need further LDL cholesterol lowering," said Sean E. Harper, MD, executive vice president of Research and Development at Amgen.

The Repatha cardiovascular outcomes study (FOURIER) demonstrated that adding evolocumab to optimized statin therapy resulted in a statistically significant 20% (P < 0.001) reduction in major adverse cardiovascular events (MACE) 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 < 0.001) 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 six months and accruing through the median 2.2 years of the study.

Patients on evolocumab experienced a reduction in the risk of heart attack (27%, nominal P < 0.001), stroke (21%, nominal P = 0.01) and coronary revascularization (22%, nominal P < 0.001). 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 safety profile of evolocumab 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 (HeFH). Common adverse reactions included diabetes mellitus, nasopharyngitis, and upper respiratory tract infection.

The FDA provided priority review to Amgen’s supplemental biologics license application for the new indication.

Source: Amgen; December 1, 2017.