BACKGROUND: Evolocumab (AMG 145), a monoclonal antibody against proprotein 
convertase subtilisin/kexin type 9 (PCSK9), significantly reduced low-density 
lipoprotein cholesterol (LDL-C) in phase 2 studies of 12 weeks' duration. The 
longer-term efficacy and safety of PCSK9 inhibition remain undefined.
METHODS AND RESULTS: Of 1359 randomized and dosed patients in the 4 evolocumab 
phase 2 parent studies, 1104 (81%) elected to enroll into the Open-Label Study 
of Long-term Evaluation Against LDL-C (OSLER) study. Regardless of their 
treatment assignment in the parent study, patients were randomized 2:1 to 
receive either open-label subcutaneous evolocumab 420 mg every 4 weeks with 
standard of care (SOC) (evolocumab+SOC, n=736) or SOC alone (n=368). Ninety-two 
percent of patients in the evolocumab+SOC group and 89% of patients in the SOC 
group completed 52 weeks of follow-up. Patients who first received evolocumab in 
OSLER experienced a mean 52.3% [SE, 1.8%] reduction in LDL-C at week 52 
(P<0.0001). Patients who received 1 of 6 dosing regimens of evolocumab in the 
parent studies and received evolocumab+SOC in OSLER had persistent LDL-C 
reductions (mean reduction, 50.4% [SE, 0.8%] at the end of the parent study 
versus 52.1% [SE, 1.0%] at 52 weeks; P=0.31). In patients who discontinued 
evolocumab on entry into OSLER, LDL-C levels returned to near baseline levels. 
Adverse events and serious adverse events occurred in 81.4% and 7.1% of the 
evolocumab+SOC group patients and 73.1% and 6.3% of the SOC group patients, 
respectively.
CONCLUSION: Evolocumab dosed every 4 weeks demonstrated continued efficacy and 
encouraging safety and tolerability over 1 year of treatment in the largest and 
longest evaluation of a PCSK9 inhibitor in hypercholesterolemic patients to 
date.
CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov. Unique identifier: 
NCT01439880.