Homozygous FH responds to alirocumab

In the ODYSSEY HoFH study, alirocumab significantly reduced low-density lipoprotein cholesterol (LDL-C) in the largest randomised, placebo-controlled clinical trial looking at lipid-lowering in adults with homozygous familial hypercholesterolaemia (HoFH) to date.

The primary objective of the study, presented by Prof. Dirk Blom (University of Cape Town, South Africa), was to demonstrate the reduction of LDL-C after subcutaneous alirocumab every 2 weeks compared with placebo after 12 weeks of treatment [1].

The double-blinded trial included 69 adults with genetically confirmed HoFH randomised 2:1 to the PCSK9 inhibitor alirocumab dosed at 150 mg every 2 weeks or placebo while on concurrent intensive background lipid lowering with statins and/or other agents including ezetimibe. Patients’ LDL-C levels at baseline were 300 mg/dL, which is approximately 350% the target level.

Although no patient reached target LDL-C levels, the average observed reduction in LDL-C in the alirocumab arm was 63 mg/dL, which met the primary endpoint and is clinically relevant in this patient group. Of the patients on alirocumab, 57% had at least a 30% reduction in LDL at 12 weeks, and 27% had at least a 50% reduction. Alirocumab also affected other atherogenic lipids, with an approximate 20% reduction from baseline in lipoprotein(a), a 23% decrease in apolipoprotein B, and a 25% reduction in non-HDL cholesterol.

Invited discussant Prof. Raul Santos (University of São Paulo, Brazil) concluded: "Certainly, PCSK9 inhibitors should be the next step after statins and ezetimibe. They are much less expensive and more available than apheresis."

1. 
   
   1. Blom D, et al. Abstract 411-10. ACC/WCC 28-30 March 2020.

Posted on 8 September 202026 July 2024