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Cholesterol Drug Alirocumab (Praluent) Wins ‘Priority Review’ Designation

FDA’s approval decision expected in July

The FDA has accepted for priority review the biologics license application (BLA) for alirocumab (Praluent, Regeneron Pharmaceuticals). Under the Prescription Drug User Fee Act (PDUFA), the goal for a priority review is 6 months, for a target action date of July 24, 2015.

Alirocumab is an investigational monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) that is intended for the treatment of patients with hypercholesterolemia. It is administered via subcutaneous injection. By inhibiting PCSK9, a determinant of circulating low-density lipoprotein cholesterol (LDL-C) levels in the blood, alirocumab has been shown in preclinical studies to increase the number of LDL receptors on hepatocytes, thereby lowering LDL-C levels.

PCSK9 binds to LDL receptors, resulting in their degradation so that fewer are available on liver cells to remove excess LDL-C from the blood. Moreover, traditional LDL-lowering therapies, such as statins, stimulate the production of PCSK9, which limits their own ability to lower LDL-C. Blocking the PCSK9 pathway is therefore a potential mechanism for lowering LDL-C.

The BLA for alirocumab contains data from more than 5,000 patients, including 10 phase III ODYSSEY trials. Together with additional ongoing studies, including ODYSSEY OUTCOMES, the ODYSSEY clinical trial program will include more than 23,500 patients at more than 2,000 study centers in double-blind, randomized, placebo-and active-controlled trials ranging from 24 weeks to approximately 5 years.

In the initial ODYSSEY trial (ODYSSEY MONO), the mean reduction in LDL-C from baseline to week 24 –– the study’s primary efficacy endpoint –– was significantly greater in patients randomly assigned to receive alirocumab compared with patients treated with ezetimibe (47.2% vs. 15.6%, respectively; P < 0.0001). In this study, which employed a dose increase (up-titration) for patients who did not achieve an LDL-C level of 70 mg/dL, most of the patients remained on the initial low dose of alirocumab (75 mg).

The most common class of adverse events was infections (39.2% with ezetimibe vs. 42.3% with alirocumab), which included nasopharyngitis, influenza, and upper respiratory tract infection. Injection-site reactions occurred in less than 2% of patients in both treatment groups.

The FDA has conditionally accepted Praluent as the trade name for alirocumab. The safety and efficacy of alirocumab have not been fully evaluated by any regulatory authority.

Sources: Regeneron; January 26, 2015; and Regeneron; October 13, 2013.

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