FDA Approval Status of PCSK9 Inhibitors

In June, 2015, two PCSK9 inhibitors, evolocumab and alirocumab, were recommended for approval by the United States Food and Drug Administration (FDA) advisory panel.9,10 On July 24, 2015, the FDA approved alirocumab for use, in addition to diet and maximally tolerated statin therapy, in adult patients with heterozygous familial hypercholesterolemia or patients with clinical atherosclerotic cardiovascular disease such as heart attacks or strokes, who require additional lowering of LDL cholesterol.11 The approval was based on a review of efficacy and safety data of five placebo-controlled trials, involving 2,476 participants treated with alirocumab. All participants had familial hypercholesterolemia or were otherwise at high risk for heart attack or stroke, and were taking maximally tolerated doses of a statin, with or without other lipid-modifying therapies. Subjects treated with alirocumab had an average reduction in LDL cholesterol between 36% and 59%, as compared to placebo.11 

On August 28, 2015, the FDA approved evolocumab for use in addition to diet and maximally-tolerated statin therapy in adults with heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, or clinical atherosclerotic cardiovascular disease, such as heart attacks or strokes, who require additional lowering of low-density lipoprotein cholesterol (LDL-C). The safety and efficacy of evolocumab were studied in one 52-week placebo-controlled trial and eight 12-week placebo-controlled trials in patients with primary hyperlipidemia; two specifically enrolled patients with heterozygous familial hypercholesterolemia and one enrolled patients with homozygous familial hypercholesterolemia. In one of the trials (n=329), patients with heterozygous familial hypercholesterolemia were randomized to evolocumab or placebo for 12 weeks. An average LDL-C reduction of 60% was seen in the evolocumab group compared to placebo.


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