FDA advisory committee okays two monoclonal antibody formulations in two days for treatment of hypercholesterolemia.
FDA’s Endocrinologic and Metabolic Drugs Advisory Committee voted 13 to 3 on June 9 in favor of the approval of alirocumab (Praluent Injection), a new first-in-class cholesterol-lowering agent for patients with hypercholesterolemia. On June 10, the committee recommended approval of evolocumab (Repatha), another agent in the new class of lipid-altering drugs, in a vote of 11 to 4.
Both alirocumab, developed by Regeneron Pharmaceuticals and Sanofi, and evolocumab, developed by Amgen, are investigational human monoclonal antibodies that target proprotein convertase subtilisin/kexin type 9 (PCSK9) in the liver. By blocking this protein, the drugs can lower the amount of low-density lipoprotein cholesterol (LDL-C) in the blood.
More than 5,000 patients who participated in a total of 10 phase 3 double-blind trials for the evaluation of alirocumab were followed for six months to two years. The clinical data from the ODYSSEY phase 3 studies demonstrated the efficacy of alirocumab in reducing LDL-C. The most common side effects in patients who received alirocumab during the trials were injection-site reaction and pruritus.
“The discovery of PCSK9 as a powerful regulator of cholesterol levels and cardiovascular disease was one of the most important human genetic advances in the last decade,” said George D. Yancopoulos, MD, PhD, chief scientific officer of Regeneron and president of Regeneron Laboratories. “Today’s outcome brings us one step closer to translating this genetics-based discovery into a treatment that may help the many patients in need of additional cholesterol lowering.”
FDA is expected to review the biologics license application for alirocumab by July 24, 2015.
“If approved by the FDA, Praluent is expected to be the first fully human monoclonal antibody targeting PCSK9 in the U.S.,” announced a press statement from Regeneron and Sanofi.
Amgen presented its clinical trial data of evolocumab, which included 10 phase 3 studies of approximately 6,800 patients, of whom more than 4,500 had high cholesterol.
The studies evaluated the efficacy and safety of evolocumab in patients who had elevated cholesterol, including those taking statins with or without lipid-lowering therapies; patients who could not tolerate statins, patients with heterozygous familial hypercholesterolemia, and patients with homozygous familial hypercholesterolemia.
“In data from the clinical program to date, Repatha has demonstrated consistent, significant and durable reduction in LDL-C levels with favorable effects on other lipid parameters in approximately 6,000 patients with primary hyperlipidemia and mixed dyslipidemia,” Amgen reported.
Amgen noted that its clinical data showed that evolocumab reduced LDL-C by about 55% to 75% compared with placebo and by about 35% to 45% compared with ezetimibe. For patients with homozygous familial hypercholesterolemia, the reduction in LDL-C was about 30% when treated with evolocumab compared to placebo.
Common adverse events for trial patients taking evolocumab included nasopharyngitis, upper respiratory tract infection, back pain, arthralgia, influenza, and nausea, Amgen reported.
The panel unanimously agreed that evolocumab should be approved for patients with homozygous familial hypercholesterolemia, a rare and serious genetic disorder. They also voted 11 to 4 for the drug to be used in patients who need more than just a statin for lipid-lowering.
FDA is expected to review the biologics license application for evolocumab by August 27, 2015.