Long-term safety and efficacy of alirocumab in patients with heterozygous familial hypercholesterolemia: An open-label extension of the ODYSSEY program

Atherosclerosis. 2018 Nov:278:307-314. doi: 10.1016/j.atherosclerosis.2018.08.036. Epub 2018 Sep 1.

Abstract

Background and aims: ODYSSEY OLE (open-label extension; NCT01954394) included patients diagnosed with heterozygous familial hypercholesterolemia (HeFH), receiving maximally tolerated statins, who had completed one of four Phase 3 double-blind parent studies (all 18 months' duration), with the aim to assess longer-term safety and efficacy of alirocumab.

Methods: Patients received starting dose alirocumab 75 mg every 2 weeks (Q2W; patients from FH I, FH II, and LONG TERM) or alirocumab 150 mg Q2W (patients from HIGH FH). Low-density lipoprotein cholesterol (LDL-C) levels were blinded to the patient and physician until Week 8; from Week 8, LDL-C levels were communicated to physicians. From Week 12, dose adjustment from 75 to 150 mg Q2W, or vice versa, was possible per physician's clinical judgment according to patient's LDL-C levels.

Results: Patients who had received alirocumab (n = 655) compared with placebo (n = 330) in the parent studies exhibited similar rates of treatment-emergent adverse events (TEAEs; 87.3% vs. 83.9%) during OLE (2.5 years median alirocumab exposure). Overall, 33 patients (3.4%) experienced TEAEs leading to permanent treatment discontinuation. At Week 8, alirocumab reduced mean LDL-C by 44.2% (reduction from 151.9 mg/dL at parent study baseline to 84.9 mg/dL); reduction in LDL-C was consistent to Week 96 of OLE. Reductions in lipid parameters were similar regardless of treatment allocation in the parent study.

Conclusions: In patients with HeFH, no unexpected long-term safety concerns were observed with alirocumab compared with previously published data; durability of LDL-C-lowering over 3 years (including 1.5 years of parent trials) was demonstrated.

Keywords: Alirocumab; Cardiovascular disease; Lipid-lowering therapy; Low-density lipoprotein cholesterol; Open-label extension; PCSK9.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Body Mass Index
  • Cholesterol, LDL / metabolism
  • Diabetes Complications
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Heterozygote
  • Humans
  • Hyperlipoproteinemia Type II / drug therapy*
  • Hyperlipoproteinemia Type II / genetics*
  • Male
  • Middle Aged
  • Patient Safety

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Cholesterol, LDL
  • alirocumab

Associated data

  • ClinicalTrials.gov/NCT01954394