Elsevier

Journal of Clinical Lipidology

Volume 8, Issue 6, November–December 2014, Pages 554-561
Journal of Clinical Lipidology

Original Article
Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in statin-intolerant patients: Design and rationale of ODYSSEY ALTERNATIVE, a randomized phase 3 trial

https://doi.org/10.1016/j.jacl.2014.09.007Get rights and content
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open access

Highlights

  • Includes patients unable to tolerate at least 2 statins, 1 at lowest starting dose.

  • Intolerance reaffirmed via placebo run-in and blinded statin rechallenge.

  • The only PCSK9 inhibitor study in a well-defined statin-intolerant population.

  • Alirocumab will be compared with ezetimibe.

Background

Statin intolerance has been a major limitation in the use of statins, especially at higher doses. New effective treatments are needed for lowering low-density lipoprotein cholesterol (LDL-C) in patients who cannot tolerate daily statin doses.

Objective

ODYSSEY ALTERNATIVE (NCT01709513) evaluates efficacy and safety of alirocumab, a fully human proprotein convertase subtilisin/kexin type 9 monoclonal antibody, in patients with well-documented statin intolerance and moderate to very high cardiovascular risk.

Methods

This is a phase 3, multicenter, randomized, double-blind, double-dummy study in statin-intolerant patients. Intolerance was defined as inability to take at least 2 different statins because of muscle-related adverse events (AEs), 1 at the lowest approved starting dose. Patients first received single-blind subcutaneous and oral placebo for 4 weeks, and were withdrawn if they developed muscle-related AEs after the placebo treatment. Continuing patients were randomized (2:2:1 ratio) to alirocumab 75 mg self-administered via single 1 mL prefilled pen every 2 weeks or ezetimibe 10 mg/day or atorvastatin 20 mg/day (statin rechallenge), for 24 weeks. Alirocumab dose was increased to 150 mg every 2 weeks (also 1 mL) at week 12 depending on week 8 LDL-C level. The primary endpoint is percent change in LDL-C from baseline to week 24 by intent-to-treat analysis. Muscle-related AEs were assessed by spontaneous patient reports and clinic queries.

Results

A total of 314 patients have been randomized.

Conclusions

This is the first and only study of a new class of LDL-C–lowering agents in patients selected with a rigorously documented intolerance to statins, using a placebo run-in and statin control arm.

Keywords

Alirocumab
Ezetimibe
Hypercholesterolemia
PCSK9
Phase 3 clinical trial
Statin intolerance
Muscle symptoms
Statin myopathy

Cited by (0)

Funding: This study is funded by Sanofi and Regeneron Pharmaceuticals, Inc.