Abstract 16849: Alirocumab Dosing in a Real World Setting: Data From an Open-label Treatment Extension to the ODYSSEY Program for Patients With Heterozygous Familial Hypercholesterolemia
Introduction: ODYSSEY OLE (NCT01954394) is an open-label extension (OLE) study of four Phase 3 clinical trials (FH I, FH II, LONG TERM [LTS] and HIGH FH) evaluating long-term efficacy and safety of alirocumab (ALI) in patients with heterozygous familial hypercholesterolemia (HeFH) over up to 3.5 years of treatment.
Objective: ALI can be administered as 75 or 150 mg Q2W, but how this dosing strategy is applied in daily practice is largely unknown. We assessed dosing strategies used during OLE.
Methods: Patients were on maximally tolerated statin +/- other lipid-lowering therapy. Patients started on ALI 75 mg Q2W (patients enrolled from HIGH FH started OLE with 150 mg Q2W and were not analyzed here). Physicians could adjust the ALI dose based on clinical judgment and LDL-C level; if further LDL-C reduction was required the ALI dose could be increased to 150 mg Q2W.
Results: 909 patients (mean age 54.6 years, 56.1% male) with HeFH were analyzed. At OLE entry, HeFH patients from LTS (n=318) had a higher mean baseline LDL-C (161.7 mg/dL) than those from FH I (n=392; 106.7 mg/dL) and FH II (n=199; 87.0 mg/dL). These values reflect both patients receiving placebo during the parent studies as well as 8 weeks off-treatment for those enrolled from LTS (those from FH I/II began OLE on completing double-blind treatment). 868 patients (95.5%) completed ≥1 year of treatment. At time of analysis, 50/909 (5.5%) had discontinued treatment (20 [2.2%] due to adverse events).
During OLE, 59.1% of patients remained on ALI 75 mg Q2W and in 40.9% the dose was increased to 150 mg Q2W. Median time to first dose increase was 12.6 weeks and in nearly all cases was due to LDL-C level being deemed too high. Mean LDL-C in patients maintained on 75 mg Q2W during OLE was 67.6 mg/dL. For those who received a dose increase to 150 mg Q2W, mean LDL-C was 128.7 mg/dL prior to dose adjustment.
Overall, 77.8% of patients reported any TEAE, a rate similar to the ALI and placebo arms in the parent studies. Injection site reactions were reported by 5.4%, neurological TEAEs by 2.0% and neurocognitive TEAEs by 1.1% of patients.
Conclusions: In this real world setting, ALI 75 mg Q2W provided sufficient control of LDL-C level in a majority of HeFH patients, with dose increase to 150 mg Q2W used for those requiring greater LDL-C reduction.
Author Disclosures: G. Hovingh: Research Grant; Significant; GKH is holder of a Vidi grant [016.156.445] from the Netherlands Organisation for Scientific Research (NWO), GKH is supported by CardioVascular Research Initiative [CVON2011-19; Genius], the European Union [Resolve: FP7-305707 and TransCard: FP7-603091-2]. Other Research Support; Significant; Aegerion, AMGEN, Sanofi. Speakers Bureau; Modest; Amgen, Aegerion, Sanofi, Regeneron, Pfizer. Consultant/Advisory Board; Modest; Amgen, Aegerion, Sanofi, Regeneron, Pfizer. J.R. Guyton: Research Grant; Modest; Amarin, Amgen. Research Grant; Significant; Regeneron, Sanofi. Consultant/Advisory Board; Modest; Amgen, FH Foundation. G. Langslet: Speakers Bureau; Modest; Sanofi, Amgen, Boehringer Ingelheim, Janssen. Expert Witness; Modest; Sanofi, Amgen, Boehringer Ingelheim, Janssen. R. Dufour: Research Grant; Significant; Amgen, Sanofi, Pfizer, Ionis, Regeneron, Orion. Speakers Bureau; Modest; Amgen, Sanofi. Consultant/Advisory Board; Modest; Amgen, Sanofi, Janssen, Aegerion, Regeneron. M.T. Baccara-Dinet: Employment; Significant; Sanofi. C. Din-Bell: Employment; Significant; Sanofi. G. Manvelian: Employment; Significant; Regeneron Pharmaceuticals Inc. M.A. Farnier: Other Research Support; Significant; Sanofi, Regeneron, Amgen, Merck and Co. Speakers Bureau; Modest; Mylan. Speakers Bureau; Significant; Sanofi, Regeneron, Amgen, Merck and Co, Pfizer. Consultant/Advisory Board; Modest; Eli Lilly, AstraZeneca, Kowa, Akcea/Ionis. Consultant/Advisory Board; Significant; Sanofi, Regeneron, Pfizer, Amgen, Merck and Co.
- © 2016 by American Heart Association, Inc.