More Promising Results for PCSK9 Inhibitors

Interest in the proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors is intensifying as large phase 3 trials move toward completion and anticipation builds about FDA rulings. Meanwhile, smaller industry-sponsored trials continue to offer hints of how the drugs may affect outcomes.

The ODYSSEY LONG TERM trial, a phase 3 randomized, double-blind, placebo-controlled study of alirocumab, enrolled 2341 patients with heterozygous familial hypercholesterolemia or established coronary disease from 320 sites in 27 countries. Patients had LDL cholesterol levels of 70 mg/dL or higher and were receiving a statin at the maximally tolerated dose. The drug was discontinued in 28% of the alirocumab group and 25% of the placebo group. At 24 weeks, the mean percentage change in LDL, the primary endpoint, was −61% in the alirocumab group and +0.8% in the placebo group. Cardiovascular events occurred in 4.6% of the alirocumab group and 5.1% of the placebo group.

The OSLER long-term follow-up trial enrolled patients who had completed one of 12 open-label, randomized trials of evolocumab. The parent studies had different entry criteria, but the follow-up trial required that patients had not experienced an adverse event leading to discontinuation of the medication, were stable, and did not need unblinded lipid measurements. They were randomized to evolocumab with standard therapy or to standard therapy alone. At 12 weeks, evolocumab was associated with a 61% reduction in LDL compared with standard therapy. Serious adverse effects were similar in the two groups; rates of cardiovascular events at 1 year were 0.95% in the evolocumab group and 2.18% in the standard-therapy group.