FDA Advisory Committee Recommends Approval for Amgen's Repatha PCSK9 Inhibitor

June 10, 2015—The US Food and Drug Administration's (FDA's) Endocrinologic and Metabolic Drugs Advisory Committee has voted to recommend approval of Amgen's Repatha (evolocumab) for the treatment of high cholesterol. The FDA has set a target action date of August 27, 2015 for the Repatha biologics license application.

Repatha is an investigational fully human monoclonal antibody that inhibits PCSK9 (proprotein convertase subtilisin/kexin type 9). Repatha is designed to bind to PCSK9 and inhibit PCSK9 from binding to low-density lipoprotein cholesterol (LDL-C) receptors on the liver surface.

After the advisory committee's review and favorable vote, the company made the following statement: "It is clear from today's discussion with the FDA's Endocrinologic and Metabolic Drugs Advisory Committee that there is a critical need for additional treatment options for patients who are unable to control their high cholesterol despite currently available therapies. Elevated LDL-C is recognized as a major risk factor for cardiovascular disease (CVD), and approximately 33% of patients at high risk for CVD cannot adequately lower their LDL-C levels with statins and/or other currently approved lipid-lowering therapies. We look forward to continuing to work with the FDA as they complete their review of the Biologics License Application for Repatha (evolocumab), in hopes of bringing this important new medicine to patients with high cholesterol."

In a press release issued before the Endocrinologic and Metabolic Drugs Advisory Committee meeting, Amgen advised that it would present Repatha clinical trial data from approximately 6,800 patients, including more than 4,500 patients with high cholesterol in 10 phase 3 trials. The phase 3 studies evaluated the efficacy and safety of Repatha in patients with elevated cholesterol, including patients on statins with or without other lipid-lowering therapies, patients who cannot tolerate statins, patients with heterozygous familial hypercholesterolemia, and patients with homozygous familial hypercholesterolemia.

According to the company, Repatha is being evaluated in the large, comprehensive PROFICIO clinical trial program that includes 22 clinical trials, with a combined planned enrollment of approximately 35,000 patients.

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. In these studies, Repatha reduced LDL-C by approximately 55% to 75% compared with placebo and by approximately 35% to 45% compared with ezetimibe. In patients with homozygous familial hypercholesterolemia, Repatha reduced LDL-C by approximately 30% compared with placebo. Reduction of LDL-C was maintained with long-term treatment.

The adverse event profile for Repatha was similar overall to that of the control groups. The most common adverse events for the Repatha group versus any control group were nasopharyngitis (5.9% vs 4.8%), upper respiratory tract infection (3.2% vs 2.7%), back pain (3% vs 2.7%), arthralgia (2.3% vs 2.2%), influenza (2.1% vs 2%), and nausea (2.1% vs 1.8%), reported the company.