OSLER-1 trial demonstrates efficacy, safety of evolocumab in hypercholesterolemia

CHICAGO – Treatment with evolocumab decreased LDL cholesterol consistently without escalating the rate of adverse events or leading to the development of neutralizing antibodies, according to findings from the OSLER-1 trial presented at American Heart Association Scientific Sessions.

“Evolocumab [Repatha, Amgen] and other monoclonal antibodies against PCSK9 reduced major adverse CV outcomes in clinical trials of patients with CV disease treated up to a median of 2.8 years,” the researchers wrote. “OSLER-1 evaluated long-term evolocumab treatment in a diverse population of [patients with hypercholesterolemia].”

Michael J. Koren, MD, FACC, FAPCR, CPI, practicing cardiologist and chief executive officer at Jacksonville Center for Clinical Research in Jacksonville, Fla., and colleagues included 1,324 patients in the trial. Participants were randomly assigned to enter the standard-of-care controlled period for 1 year after enrollment in one of five prior double-blind, controlled studies of evolocumab. The analysis presented at AHA included 1,255 patients who remained in OSLER-1 during the evolocumab plus standard-of-care treatment period, which began at the start of year 2. That analysis included 1,255 patients. The mean age was 57 years; 53% of participants were female.

In the first year of the trial, Koren and colleagues randomly assigned patients in a 2:1 ratio to open-label treatment with evolocumab 420 mg per month plus standard-of-care treatment compared with standard-of-care treatment only. More patients (n = 882) were enrolled in the evolocumab arm compared with the standard-of-care treatment arm (n = 442). After the first year, all patients received extended, monthly evolocumab therapy plus standard-of-care treatment. The researchers examined the impact of evolocumab on lipids and safety outcomes, including antidrug antibodies, over the 5-year study period.

Treatment with evolocumab decreased median LDL cholesterol by 61% in year 1, 59% in year 2, 59% in year 3, 59% in year 4 and 58% in year 5. The analysis included 818 patients in year 1, 1,122 patients in year 2, 1,059 patients in year 3, 1,012 patients in year 4 and 870 patients in year 5.

Adverse events occurred in 79% of patients in year 1, 74% of patients in year 2, 71% of patients in year 3, 67% of patients in year 4 and 65% of patients in year 5. Serious adverse events occurred in 7%, 7%, 8%, 7% and 7%, respectively, of patients over the same time period. Adverse events that resulted in drug discontinuation occurred in 2.8%, .8%, 1.3%, 1% and .2% of patients each year from years 1 to 5.

Transiently positive tests for binding antidrug antibodies during year 1 were seen in two patients in the standard-of-care arm and two patients in the evolocumab arm. There were no subsequent or novel reports of binding or neutralizing antidrug antibodies noted after that point, according to Koren and colleagues.

“In OSLER-1, the longest study of a PCSK9 inhibitor to date, evolocumab consistently reduced LDL cholesterol with no increase in adverse events over time and no neutralizing antibodies,” the researchers wrote. - by Julia Ernst, MS

Reference:

Koren MJ, et al. Abstract 118. Presented at: American Heart Association Scientific Sessions; Nov. 10-12, 2018; Chicago.

Disclosures: Koren reports consultant/advisory board roles with Amgen, Pfizer, Regeneron and Sanofi and receiving research grants from Amgen, Pfizer, Regeneron and Sanofi. Please see the abstract for all other authors’ relevant financial disclosures.