Regulatory Decision Summary for Praluent

Cardiovascular Risk Reduction:

Atherosclerotic cardiovascular disease (ASCVD) and associated clinical manifestations (e.g., myocardial infarction (MI), ischemic stroke) are the leading cause of morbidity and mortality throughout the world.

Authorization of Praluent (alirocumab injection) in this submission was based upon the ODYSSEY OUTCOMES study, a double-blind, placebo-controlled, event driven, superiority trial, which included 18,924 adult patients (9462 alirocumab; 9462 placebo) who had experienced a recent acute coronary syndrome (ACS) event prior to randomization and who primarily, despite an intensive lipid lowering therapy (i.e., statins), did not reach pre-specified levels of serum cholesterol and its lipoprotein carriers (e.g., low-density lipoprotein [LDL-C]). All patients were randomized 1:1 to receive either Praluent 75 mg or placebo once every two weeks.

The primary efficacy endpoint was the time from randomization to first occurrence of a major ASCVD event including coronary heart disease (CHD) death, non-fatal MI, fatal and non-fatal ischemic stroke, and unstable angina (UA) requiring hospitalization. Praluent resulted in a 15% reduction in risk of major ASCVD events in combination with a maximum tolerated dose of a statin, with or without other lipid lowering therapies, in adults with established cardiovascular disease. The treatment effect was driven by a reduction in risk of non-fatal MI, fatal and non-fatal ischemic stroke, and UA requiring hospitalization in patients. Praluent additionally resulted in a 15% reduction in the risk of death from any cause.

The most frequently reported treatment-emergent adverse events (≥5% of subjects in either treatment group) were non-cardiac chest pain (7.0% alirocumab vs. 6.8% placebo), hypertension (6.0% vs. 6.5%), nasopharyngitis (6.0% vs. 5.6%), myalgia (5.6% vs. 5.3%), blood creatine phosphokinase increased (4.9% vs. 5.2%), and angina pectoris (4.5% vs. 5.0%). The only TEAE with an incidence of ≥2% in the alirocumab group and a ≥0.5% difference compared with placebo was injection site reaction (2.8% vs. 1.4%) and immunogenicity [anti-drug antibody] (5.5% vs. 1.6%).

The recommended dose of Praluent is 75 mg one every 2 weeks. A dosing interval of 300 mg every 4 weeks may be considered if the patient who may benefit from less frequent dosing. View the Praluent Product Monograph for details.

Primary Hyperlipidemia:

Four clinical trials demonstrated a positive benefit-risk profile for Pralient use either along or in combination with statins and/or other lipid-modifying therapies in patients with primary hyperlipidemia. These trials (ALTERNATIVE, MONO, CHOICE I, AND COMBO II) included 1,940 patients with either familial or non-familial primary hyperlipidemia and moderate to very severe cardiovascular risk profile. Two trials included patients that were not on background statins and one trial included patients that were not on statins or any other lipid lowering medications.

All four trials demonstrated reduction of LDL-C levels from baseline of 45-52% with Praluent 75 mg (with up-titration to 150 mg at Week 12 for qualifying patients) after 24 weeks of treatment. The safety profile was consistent with the established profile in patients with heterozygous familial hyperlipidemia.

Based on these studies, there is a positive benefit-risk profile for the use of Praluent alone or in combination with statins and/or other lipid lowering medications or as monotherapy when statins are contraindicated in patients with familial or non-familial primary hyperlipidemia.