Physicians' Academy for Cardiovascular Education

Long-term PCSK9 inhibition consistently lowers LDL-C in open-label extension study

Long-term Low-Density Lipoprotein Cholesterol–Lowering Efficacy, Persistence, and Safety of Evolocumab in Treatment of Hypercholesterolemia

Results Up to 4 Years From the Open-Label OSLER-1 Extension Study

Koren MJ, Sabatine MS, Giugliano RP, et al. - JAMA Cardiol 2017; published online ahead of print

Background

Two PCSK9 inhibitors, evolocumab and alirocumab, are approved as lipid-lowering therapies when LDL-C is not adequately controlled with maximally tolerated statin therapy, in patients with cardiovascular disease or heterozygous familial hypercholesterolemia (FH), and evolocumab is also approved in patients with homozygous FH [1-4]. The development of a third PCSK9 antibody, bococizumab, was discontinued, due to inadequate long-term efficacy, and higher levels of immunogenicity and injection-site reactions [5].

In this analysis, the long-term lipid-lowering efficacy and safety of evolocumab were evaluated in the still ongoing open-label extension OSLER-1, an extension on 5 double-blind phase 2 parent studies performed at 192 sites in 18 countries, for up to 4 years. Of the 1650 eligible patients who completed a parent study without having experienced a serious adverse event, 1324 (80.2%) continued the OSLER-1 extension study. Of those, 882 patients were randomised to evolocumab plus standard of care (SOC) and 442 patients to SOC alone.

Main results

Conclusion

In OSLER-1, an open-label extension study of 5 double-blind phase 2 parent studies, evolocumab consistently lowered LDL-C levels for an average of 44 months, in a diverse patient population with hypercholesterolemia. There were no concerning safety signals and no neutralising antibodies. These data suggest that long-term evolocumab therapy is beneficial and well tolerated.

Editorial comment

In this editorial article, Stone points out the limitations of the study of Koren et al, which include the lack of a placebo group, the restricted sample size, and the open-label design, in which responders dominate the results. The author concludes: ‘What is new is not the substantial initial LDL-C level lowering seen with PCSK9 inhibitors, but the maintenance of that lowering for up to 4 years with evolocumab. It is reassuring to find no significant levels of measured neutralizing antibodies with this fully human PCSK9 inhibitor. The adherence achieved in this open-label extension study is adequate, but it should be noted that participants were shielded from the current high cost of these drugs. It is hoped that if outcome trial data are shown to be beneficial, cost will not be a limiting factor for those who would have the largest incremental benefit.’

References

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Find this article on line at JAMA cardiol