Koren M.J., Giugliano R.P., Raal F.J., Sullivan D., Bolognese M., Langslet G., Civeira F., Somaratne R., Nelson P., Liu T., Scott R., Wasserman S.M., Sabatine M.S.
Jacksonville Center for Clinical Research, University Blvd S, Ste 1, Jacksonville, FL 32216, United States; TIMI Study Group, Division of Cardiovascular Medicine, Harvard Medical School, Boston, MA, United States; University of the Witwatersrand, Division of Endocrinology and Metabolism, Faculty of Health Sciences, Johannesburg, South Africa; Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Camperdown, Australia; Bethesda Health Research Center, Bethesda, MD, United States; Lipid Clinic, Oslo University Hospital, Oslo, Norway; Hospital Universitario Miguel Servet, Zaragoza, Spain; Amgen Inc, Thousand Oaks, CA, United States
Koren, M.J., Jacksonville Center for Clinical Research, University Blvd S, Ste 1, Jacksonville, FL 32216, United States; Giugliano, R.P., TIMI Study Group, Division of Cardiovascular Medicine, Harvard Medical School, Boston, MA, United States; Raal, F.J., University of the Witwatersrand, Division of Endocrinology and Metabolism, Faculty of Health Sciences, Johannesburg, South Africa; Sullivan, D., Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Camperdown, Australia; Bolognese, M., Bethesda Health Research Center, Bethesda, MD, United States; Langslet, G., Lipid Clinic, Oslo University Hospital, Oslo, Norway; Civeira, F., Hospital Universitario Miguel Servet, Zaragoza, Spain; Somaratne, R., Amgen Inc, Thousand Oaks, CA, United States; Nelson, P., Amgen Inc, Thousand Oaks, CA, United States; Liu, T., Amgen Inc, Thousand Oaks, CA, United States; Scott, R., Amgen Inc, Thousand Oaks, CA, United States; Wasserman, S.M., Amgen Inc, Thousand Oaks, CA, United States; Sabatine, M.S., TIMI Study Group, Division of Cardiovascular Medicine, Harvard Medical School, Boston, MA, United States
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. © 2013 American Heart Association, Inc.