FDA Approves Once-Monthly Dosing Option for Praluent Injection

PCSK9 inhibitor lowers low-density lipoprotein-cholesterol levels

The FDA has approved the supplemental biologics license application for a once-monthly (every four weeks) 300-mg dose of alirocumab injection (Praluent, Sanofi/Regeneron) for the treatment of adults with high low-density lipoprotein-cholesterol (LDL-C).

Alirocumab is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require additional lowering of LDL-C The effect of alirocumab on cardiovascular morbidity and mortality has not been determined.

The 300-mg dose is administered via two 150-mg injections at two different injection sites. Each 1-mL prefilled pen delivers 150 mg of alirocumab in 20 seconds or less.

The once-monthly dose of alirocumab was approved by the FDA based on results from the phase 3 ODYSSEY CHOICE I study, which compared alirocumab (300 mg every four weeks) with placebo in patients with hypercholesterolemia who were also receiving a concomitant statin. In the United States, the recommended starting dosage for alirocumab is 75 mg once every two weeks administered subcutaneously, or 300 mg once every four weeks (monthly) for patients who prefer less-frequent dosing. These doses may be adjusted to a maximum of 150 mg every two weeks for patients requiring greater LDL-C reductions.

Alirocumab is contraindicated in patients with a history of a serious hypersensitivity reaction to the drug. Allergic reactions have included hypersensitivity vasculitis and hypersensitivity reactions requiring hospitalization. In the ODYSSEY CHOICE I study, in which all patients received an injection of alirocumab or placebo every two weeks to maintain the blind, local injection-site reactions were reported more often in patients treated with alirocumab 300 mg every four weeks compared with those receiving alirocumab 75 mg every two weeks or placebo (16.6%, 9.6%, and 7.9%, respectively).

Alirocumab inhibits the binding of proprotein convertase subtilisin/kexin type 9 (PCSK9) to LDL receptors, thereby increasing the number of available receptors on the surface of liver cells, which results in lower LDL-C levels in the blood.