The drug also cut HDL cholesterol by an average of as much as 31% from baseline, though the consequence of this effect isn’t clear. “I’m not worried about the HDL levels,” said Dr. Goldberg, who noted that changes in HDL cholesterol produced by drug treatment have often not shown discernible effects.
Reaching goals by IV or subcutaneous delivery
Another measure of evinacumab’s efficacy was the percentage of patients who fell below the LDL-cholesterol threshold of 70 mg/dL set by recommendations of the American Heart Association and American College of Cardiology for the highest risk patients, and the less than 55 mg/dL goal set for similar patients by the European Society of Cardiology. Among the subcutaneously-treated patients, 64% achieved the goal of less than 70 mg/dL, and 49% hit the goal of less than 55 mg/dL. Among those who received IV treatment, 71% fell below the 70 mg/dL threshold, and 50% dropped below 55 mg/dL.
The good efficacy shown with subcutaneous dosing is critical, noted Dr. Eckel, as this represents a new dimension for evinacumab that had previously been tested only as an IV agent in patients with homozygous FH ( N Engl J Med. 2020 Aug 20;383[8]:711-20 ).
“Subcutaneous delivery is needed for wide real world use,” Dr. Eckel noted in an interview.
Evinacumab’s role hangs on further studies
The path that evinacumab takes from here into U.S. practice is not yet clear, said Dr. Rosenson. He cited the approval earlier in 2020 of another LDL-lowering drug, bempedoic acid (Nexletol) that received U.S. regulatory approval for a similar patient population after studies that proved only lipid-lowering safety and efficacy, without any clinical-endpoint data. He wondered: “Will the [Food and Drug Administration] require a cardiovascular outcomes trial” for evinacumab?
The growing experience using the PCSK9 inhibitor antibodies to treat hyperlipidemia has made clinicians comfortable with this general approach to lipid management, but if evinacumab never accumulates similar efficacy evidence that may relegate it to the backseat compared with the PCSK9 inhibitors for quite some time, suggested Dr. Goldberg, though she said she’d be willing to prescribe evinacumab to selected patients based on lipid-lowering evidence alone.
By providing an alternative mechanism for lipid lowering, evinacumab can serve as a useful add-on for patients not reaching their LDL-cholesterol goal with more established agents, thereby providing an alternative to LDL apheresis, which now serves as the lipid-lowering therapy of last resort, said both Dr. Rosenson and Dr. Goldberg.
The study was sponsored by Regeneron, the company developing evinacumab. Dr. Rosenson has been a consultant to Regeneron, and has also been a consultant to or received research funding from Amgen, 89Bio, Corvidia, CVS Caremark, Kowa, Novartis, and The Medicines Company. Dr. Goldberg has received research grants, personal fees, and nonfinancial support from Regeneron and Sanofi, research grants from Amarin, Amgen, Ionis/AKCEA, Novartis, and Pfizer, and personal fees from AKCEA, Esperion, Merck and Novartis. Dr. Eckel has been a consultant to KOWA and Novo Nordisk.