• Michael J Koren, Robert P Giugliano, Frederick J Raal, David Sullivan, Michael Bolognese, Gisle Langslet, Fernando Civeira, Ransi Somaratne, Patric Nelson, Thomas Liu, Rob Scott, Scott M Wasserman, Marc S Sabatine, and OSLER Investigators.
• Jacksonville Center for Clinical Research, Jacksonville, FL (M.J.K.); TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (R.P.G., M.S.S.); Carbohydrate and Lipid Metabolism Research Unit, Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa (F.J.R.); Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Camperdown, Australia (D.S.); Bethesda Health Research Center, Bethesda, MD (M.B.); Lipid Clinic, Oslo University Hospital, Oslo, Norway (G.L.); Hospital Universitario Miguel Servet, Zaragoza, Spain (F.C.); and Amgen Inc, Thousand Oaks, CA (R.S., P.N., T.L., R.S., S.M.W.).
• Circulation. 2014 Jan 14;129(2):234-43.

BackgroundEvolocumab (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 ResultsOf 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.ConclusionEvolocumab 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 Urlhttp://clinicaltrials.gov. Unique identifier: NCT01439880.

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