Evolocumab Well-tolerated as Add-on for Hypercholesterolemia Therapy

Evolocumab added to standard care for hypercholesterolemia was well-tolerated in a diverse patient population, a new analysis revealed.

Evolocumab and other anti-PCSK9 antibodies reduced adverse cardiovascular outcomes in clinical trials of high-risk patients over less than three years median treatment duration,” the authors wrote in their abstract. “The Open Label Study of Long Term Evaluation Against LDL-C (OSLER-1) trial evaluated longer-term effects of evolocumab during open-label hypercholesterolemia treatment for up to five years.”

The OSLER-1 researchers enrolled 1,255 patients with hypercholesterolemia in the study and randomly assigned them to either standard of care (SOC) or to evolocumab 420 mg monthly plus standard care for one year, after which time patients were permitted to enter the all-evolocumab period for an additional four years. The primary outcomes of interest included rates of adverse events and and anti-drug antibodies over an observation period of just under five patient-years (4.951) of observation.

The 1,255 patients randomized into the year one SOC-controlled period comprised the safety analysis population. According to the study results, 1,151 patients in the efficacy analysis population progressed to the four-year evolocumab regimen at year two and beyond. According to the researchers, the evolocumab plus SOC regimen lowered mean low-density lipoprotein cholesterol (LDL-C) by as much as 56% at two years (n=1,071), 57% at three years (n=1,001), 56% at four years (n=943), and 56% at five years (n=803) from randomization. They also reported that mean baseline LDL-C decreased from 140 mg/dL to 6 mg/dL while on treatment. Yearly serious adverse event rates during the evolocumab period were comparable to those with SOC alone. Evolocumab discontinuation due adverse events occurred in 5.7% of patients.

“The OSLER-1 trial demonstrated consistently excellent LDL-C–lowering efficacy, tolerance, and safety of evolocumab, with no neutralizing antibodies detected, throughout the longest-duration study of a PCSK9 inhibitor reported to date,” the researchers wrote in their conclusion. “In patients with hypercholesterolemia, including those with severe familial forms, the anti-PCSK9 antibody evolocumab exhibits sustained efficacy without development of drug-neutralizing antibodies or other attenuating factors, and relatively infrequent adverse reactions requiring interruption of treatment.”

The researchers added that “[s]imilar long-term follow-up studies should include other novel therapies as comparators to better understand the factors that contribute most to sustained benefit over time.”

The study was published in the Journal of the American College of Cardiology.