DALLAS – Monthly treatment with a human antibody directed against the PCSK9 enzyme was safe and effective for substantially lowering low-density-lipoprotein cholesterol levels in 736 patients treated for 1 year in a controlled phase II study, the longest and largest series of patients treated with a PCSK9 antibody yet reported.
An injection of evolocumab (formerly known as Amgen 145) a human antibody to the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme once every 4 weeks led to an average 52% reduction in blood levels of LDL cholesterol after 1 year on top of background treatment with standard-of-care medications, which in many cases also included maximal statin treatment, Dr. Michael J. Koren said at the American Heart Association scientific sessions.
Dr. Michael J. Koren
In addition, the safety results for evolocumab "were very clean," he said, with no evidence that patients developed neutralizing antibody against the monoclonal antibody drug, and with injection-site reactions occurring in 5% of treated patients with one patient withdrawing because of the injection-site effect.
The Food and Drug Administration should "certainly vote to approve these drugs for familial hypercholesterolemia," said Dr. Koren, director of noninvasive cardiology at Jacksonville (Fla.) Memorial Hospital. "These are patients in whom we see a lot of complication, and we need lots of ways to lower their cholesterol."
PCSK9-inhibitor treatment of other patient populations, such as patients who are statin intolerant, will "probably need outcome studies for us to feel comfortable with widespread adoption," he added. Dr. Eckel estimated that about 4 million American patients who have been prescribed a statin can’t take the drug because of intolerance.
The Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) enrolled patients who had been enrolled in any of four prior phase II studies of evolocumab that each ran for 12 weeks. OSLER randomized 736 patients at 155 centers in 17 countries to receive 420 mg of evolocumab as a subcutaneous injection every 4 weeks in addition to standard-of-care treatment; 368 patients were assigned to standard of care only as controls. Patients averaged 56 years of age, their average LDL cholesterol level at baseline was about 140 mg/dL, and just under two-thirds of patients also received treatment with a statin.
After 1 year, 86% of the evolocumab-treated patients had an LDL cholesterol level below 100 mg/dL and 63% had their level below 70 mg/dL. In contrast, 16% and 1% respectively of patients on standard care reached these levels.
"We’re super pleased with the safety and tolerability data we’ve seen so far," Dr. Koren said. Even among the 98 patients treated with evolocumab who had their LDL cholesterol level below 25 mg/dL at 1year, the data showed no signal of increased serious adverse reactions or kidney or liver abnormalities. The only suggestion of a possible problem was a reported 9% incidence of headaches, compared with a 3% rate among patients on standard care and a 6% rate among patients on evolocumab for 1 year with LDL cholesterol levels of less than 50 mg/dL.
Concurrent with Dr. Koren’s report, the results also were published online (Circulation 2013;128 [doi:10.1161/CIRCULATIONAHA.113.007012]).
OSLER was sponsored by Amgen. Dr. Koren said that he has received research support from Amgen and from Regeneron, Sanofi, Roche, and Pfizer.
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