OSLER: PCSK9 inhibitor reduced LDL at 1 year

DALLAS — Evolocumab, a fully human monoclonal antibody against PCSK9, was linked to persistent LDL reductions at 1 year, according to data presented at AHA 2013.

Michael J. Koren, MD, and colleagues enrolled 1,104 patients with hypercholesterolemia in the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) study, which examined the safety, efficacy and tolerability of evolocumab (AMG 145, Amgen). Koren said these data reflect the largest study of a PCSK9 inhibitor to date and the first time 1-year data in humans have been released for any PCSK9 inhibitor.

“Findings over 1,000 patient-years suggest a highly effective, consistent and well-tolerated therapy,” said Koren, of the Jacksonville Center for Clinical Research in Florida.

Participants had been randomly assigned and dosed in one of four previous phase 2 studies. Regardless of whether they were in the treatment or control group of their previous study, participants were randomly assigned 2:1 to receive subcutaneous evolocumab 420 mg every 4 weeks plus standard of care (n=736) or standard of care only (n=368). At 1 year, data were available for 680 participants in the evolocumab group and 327 in the control group.

LDL lowered in treatment group

Changes in LDL as measured by ultracentrifugation from baseline of the phase 2 parent study to 1 year were as follows:

Participants randomly assigned to the control groups in both the parent study and OSLER: –1.7%.
Participants randomly assigned to the control group in the parent study and the evolocumab group in OSLER: –52.3%.
Participants randomly assigned to the evolocumab group in the parent study and the control group in OSLER: –2.8%.
Participants randomly assigned to the evolocumab groups in both the parent study and OSLER: –52.1%.

“Importantly, there was no rebound effect above baseline levels during 1-year follow-up” for those who were assigned evolocumab in the parent study but not in OSLER, Koren said.

Evolocumab also was associated with helping participants reach LDL goals, Koren said. Among those with at least one measurement of LDL by ultracentrifugation after baseline and during OSLER, LDL <100 mg/dL was achieved at least once by 96% of those in the evolocumab group vs. 32.4% of controls at 1 year (P<.0001) and LDL <70 mg/dL was achieved at least once by 82.8% of those in the evolocumab group vs. 3.6 % of controls at 1 year (P<.0001). Among those who had LDL measurements by ultracentrifugation at all visits, LDL <100 mg/dL was achieved at every visit by 72.1% of those in the evolocumab group vs. 3.3% of controls at 1 year (P<.0001) and LDL <70 mg/dL was achieved at every visit by 37.8% of those in the evolocumab group vs. 0% of controls at 1 year (P<.0001).

Adverse event rates similar

Serious adverse events occurred in 7.1% of the treatment group vs. 6.3% of controls. Adverse events occurred in 81.4% of the treatment group vs. 73.1% of controls. The rates were similar “despite the fact that the evolocumab-treated patients had more face-to-face visits, which could arguably increase the reporting rate of adverse events,” Koren said. Also, no major increases in adverse events were observed in patients who reached LDL ≤50 mg/dL, he added.

OSLER was not an outcome study, but researchers adjudicated CV events, Koren said. Adjudicated CV clinical events occurred in 1.2% of those in the treatment group vs. 2.2% in the control group. – by Erik Swain

For more information:

Koren MJ. CS.03. Novel approaches to treating hypertension and atherosclerosis. Presented at: the American Heart Association Scientific Sessions; Nov. 16-20, 2013; Dallas.

Koren MJ. Circulation. 2013;doi:10.1161/CIRCULATIONAHA.113.007012.

Disclosure: The study was funded by Amgen. See the full study for a list of the researchers’ relevant financial disclosures.