The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee is scheduled to vote on June 10 on the safety and efficacy of evolocumab, an injectable medication to treat hyperlipidemia, mixed dyslipidemia and homozygous familial hypercholesterolemia (HoFH).
Evolocumab (Repatha, Amgen) is a monoclonal antibody administered subcutaneously that inhibits proprotein convertase subtilisin kexin type 9 (PCSK9). On June 9, the advisory panel voted 13-3 in favor of of alirocumab, another PCSK9 inhibitor (Praluent, Regeneron Pharmaceuticals and Sanofi Aventis).
Amgen is seeking approval for the drug to reduce low-density lipoprotein cholesterol (LDL-C) and improve other lipids. For adults with primary hyperlipidemia or mixed dyslipidemia, the proposed indication is for evolocumab to be used in combination with a statin with or without other lipid-lowering therapies. It also can be used as monotherapy or in combination with other lipid-lowering therapies for patients who are unable to take statins or cannot tolerate statins.
For patients older than 12 with HoFH, Amgen is seeking an indication for the use of evolocumab with other lipid-lowering therapies such as statins.
The doses for hyperlipidemia and mixed dyslipidemia patients are 140 mg every two weeks or 420 mg once monthly. The dose for patients with HoFH is 420 mg every two weeks or 420 mg once monthly.
In its preliminary review, the FDA found patients with hyperlipidemia and mixed dyslipidemia who received either dose of evolocumab once monthly for 12 to 52 weeks had a statistically significant reduction of approximately 60 percent.
After 12 weeks of treatment with evolocumab, patients with HoFH had a 31 percent reduction in LDL-C compared with a placebo group, which represented a statistically significant difference.
The FDA noted the studies did not represent patients at high cardiovascular risk with substantial cardiovascular disease burden when taking statins. It also mentioned it had concerns with the limited amount of safety and efficacy data for the 420 mg every two weeks dose, particularly because children could use that dose.
The FDA cited a few possible safety concerns, including pancreatitis and renal disorders, which may not be associated with evolocumab.
“Potential safety issues identified in this review could be adequately addressed in labeling and by appropriate monitoring and treatment by healthcare providers,” the FDA wrote. “If evolocumab is approved, these issues should be thoroughly explored in on-going studies.”