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.

ODYSSEY ALTERNATIVE has evaluated efficacy and safety of Alirocumab ( Praluent ), a fully human proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) monoclonal antibody, in patients with well-documented statin intolerance and moderate to very high cardiovascular risk.

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 two different statins because of muscle-related adverse events, 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Patients first received single-blind subcutaneous and oral placebo for 4 weeks, and were withdrawn if they developed muscle-related adverse reactions after the placebo treatment.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 ( Zetia ) 10 mg/day or Atorvastatin ( Lipitor ) 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 cholesterol ( LDL-C ) level.

The primary endpoint is percent change in LDL-C from baseline to week 24 by intent-to-treat analysis. Muscle-related adverse effects were assessed by spontaneous patient reports and clinic queries.

A total of 314 patients have been randomized.

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. ( Xagena )

Moriarty PM et al, J Clin Lipidol 2014;8:554-561

XagenaMedicine_2014