Eli M Roth1, Patrick M Moriarty2, Jean Bergeron3, Gisle Langslet4, Garen Manvelian5, Jian Zhao6, Marie T Baccara-Dinet7, Daniel J Rader8. 1. The Sterling Research Group, 2230 Auburn Avenue, Cincinnati, OH 45219, USA. Electronic address: eroth@sterlingresearch.org. 2. Department of Internal Medicine, Division of Clinical Pharmacology, University of Kansas Medical Center, Kansas City, KS, USA. 3. Clinique des Maladies Lipidiques, Department of Medicine, Centre Hospitalier Universitaire de Québec - Université Laval Québec, Canada. 4. Lipid Clinic, Oslo University Hospital, Oslo, Norway. 5. Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA. 6. Regeneron Pharmaceuticals, Inc., Basking Ridge, NJ, USA. 7. Sanofi, Montpellier, France. 8. Department of Medicine, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
Abstract
BACKGROUND AND AIMS: In previous phase III studies, the PCSK9 monoclonal antibody alirocumab was administered at doses of 75 or 150 mg every 2 weeks (Q2W). CHOICE I (NCT01926782) evaluated 300 mg every 4 weeks (Q4W) in patients on either maximally tolerated statin or no statin, both ± other lipid-lowering therapies. METHODS: CHOICE I included patients with hypercholesterolemia at moderate-to-very-high cardiovascular risk. Patients were randomized to alirocumab 300 mg Q4W, 75 mg Q2W (calibrator arm), or placebo for 48 weeks, with dose adjustment for either alirocumab arm to 150 mg Q2W at Week (W) 12 if at W8 LDL-C levels were >70/100 mg/dL (1.8/2.6 mmol/L) depending on cardiovascular risk or LDL-C reduction was <30% from baseline. Co-primary endpoints were percent LDL-C change from baseline to W24, and to time-averaged LDL-C over W21-24. RESULTS: Approximately two-thirds of randomized patients were receiving statins. At W12, 14.7% (no statin) and 19.3% (statin) of patients receiving alirocumab 300 mg Q4W required dose adjustment. At W24, significant LDL-C reductions from baseline were observed with alirocumab 300 mg Q4W: mean differences were -52.7% (no statin; placebo: -0.3%) and -58.8% (statin; placebo: -0.1%). Average LDL-C reductions from baseline to W21-24 were also significantly greater with alirocumab 300 mg Q4W vs. placebo in patients not receiving (-56.9% vs. -1.6%) and receiving statin (-65.8% vs. -0.8%). Treatment-emergent adverse event rates ranged from 61.1 to 75.0% (placebo) and 71.5 to 78.1% (alirocumab 300 mg Q4W). CONCLUSIONS:Alirocumab 300 mg Q4W is a viable additional treatment option in patients requiring LDL-C-lowering.
RCT Entities:
BACKGROUND AND AIMS: In previous phase III studies, the PCSK9 monoclonal antibody alirocumab was administered at doses of 75 or 150 mg every 2 weeks (Q2W). CHOICE I (NCT01926782) evaluated 300 mg every 4 weeks (Q4W) in patients on either maximally tolerated statin or no statin, both ± other lipid-lowering therapies. METHODS: CHOICE I included patients with hypercholesterolemia at moderate-to-very-high cardiovascular risk. Patients were randomized to alirocumab 300 mg Q4W, 75 mg Q2W (calibrator arm), or placebo for 48 weeks, with dose adjustment for either alirocumab arm to 150 mg Q2W at Week (W) 12 if at W8 LDL-C levels were >70/100 mg/dL (1.8/2.6 mmol/L) depending on cardiovascular risk or LDL-C reduction was <30% from baseline. Co-primary endpoints were percent LDL-C change from baseline to W24, and to time-averaged LDL-C over W21-24. RESULTS: Approximately two-thirds of randomized patients were receiving statins. At W12, 14.7% (no statin) and 19.3% (statin) of patients receiving alirocumab 300 mg Q4W required dose adjustment. At W24, significant LDL-C reductions from baseline were observed with alirocumab 300 mg Q4W: mean differences were -52.7% (no statin; placebo: -0.3%) and -58.8% (statin; placebo: -0.1%). Average LDL-C reductions from baseline to W21-24 were also significantly greater with alirocumab 300 mg Q4W vs. placebo in patients not receiving (-56.9% vs. -1.6%) and receiving statin (-65.8% vs. -0.8%). Treatment-emergent adverse event rates ranged from 61.1 to 75.0% (placebo) and 71.5 to 78.1% (alirocumab 300 mg Q4W). CONCLUSIONS:Alirocumab 300 mg Q4W is a viable additional treatment option in patients requiring LDL-C-lowering.
Authors: Amand F Schmidt; John-Paul L Carter; Lucy S Pearce; John T Wilkins; John P Overington; Aroon D Hingorani; J P Casas Journal: Cochrane Database Syst Rev Date: 2020-10-20
Authors: Erik Stroes; John R Guyton; Norman Lepor; Fernando Civeira; Daniel Gaudet; Gerald F Watts; Marie T Baccara-Dinet; Guillaume Lecorps; Garen Manvelian; Michel Farnier Journal: J Am Heart Assoc Date: 2016-09-13 Impact factor: 5.501