FDA panel recommends approving Repatha, Praluent to lower cholesterol

June 9, 2015

FDA’ s Endocrinologic and Metabolic Drugs Advisory Committee recommended this week to approve cholesterol-lowering drug evolocumab (Repatha) from Amgen in a 15-0 vote. It also voted 13-3 in favor of FDA approving Sanofi and Regeneron's Praluent (alirocumab), but most panel members called for a restricted label in high-risk patients with genetic conditions causing elevated cholesterol, rather than wider use in the general elevated cholesterol population.

FDA’ s Endocrinologic and Metabolic Drugs Advisory Committee recommended this week to approve cholesterol-lowering drug evolocumab (Repatha) from Amgen in a 15-0 vote. It also voted 13-3 in favor of FDA approving Sanofi and Regeneron's Praluent (alirocumab), but most panel members called for a restricted label in high-risk patients with genetic conditions causing elevated cholesterol, rather than wider use in the general elevated cholesterol population. 

The panel said that evolocumab should be approved in a rare disease called homozygous familial hypercholesterolemia (HoFH), a genetic disorder that causes very high cholesterol levels and can lead to heart attacks in childhood, according to an article in Forbes. The panel also said the drug could be used in other indications such as the more common heterozygous familial hypercholesterolemia (heFH), but stopped short of recommending it for the general elevated cholesterol population.

The drug manufacturers are hoping for approval for more general use in patients with elevated cholesterol who cannot tolerate statins or who cannot achieve their LDL-C targets on statin therapy alone, according to PMLive. Evolocumab has already been recommended for approval in Europe for hoFH as well as the larger target population.

In briefing documents released late last week, FDA staff generally approved of alirocumab’s safety and efficacy.

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“The benefit-risk profile of alirocumab is favorable,” according to the briefing documents prepared by FDA staff. “Alirocumab provides clinically meaningful mean reductions of LDL-C in patients not achieving adequate reductions with their existing statin, or in patients unable or unwilling to take status to achieve their LDL goals.” In clinical studies, alirocumab provided up to 63% mean reductions on top of statin therapy in patients with high cardiovascular risk who were not well-controlled, despite their current therapies.

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In a randomized, double-blind study of patients with a history of statin intolerance, alirocumab demonstrated greater efficacy than ezetimibe and a lower rate of muscle-related adverse events than with either statin or ezetimibe treatment. “These data indicate that alirocumab is a valuable treatment for patients who are unable or unwilling to take a statin and support the proposed indication in this patient population,” the document said.

Based upon currently available clinical data, Anna Goldbeck, a principal in the National Pharmacy Practice at Buck Consultants at Xerox expects utilization management controls for PCSK-9 Inhibitors to include prior authorization with step therapy as a component. 

According to Goldbeck, the criteria utilized will likely include:

  • A small segment of the population diagnosed with familial hypercholesterolemia 

  • Patients with high cholesterol not controlled by other cholesterol-lowering therapies, titrated to appropriate dosing levels

  • Patients with high cholesterol that cannot tolerate or have contraindications to other cholesterol-lowering therapies (eg, statins)

"Also, we would expect continued use of the PCSK9s to be limited to those  meeting specific reauthorization criteria, which would focus on demonstrated effectiveness [cholesterol levels]," Goldbeck said.