Does alirocumab benefit adults with familial high cholesterol levels?

This study was carried out in order to assess the safety and effectiveness of alirocumab (Praluent) in patients with homozygous familial hypercholesterolemia (FHC). The study found that these patients saw a significant reduction in cholesterol levels with the use of alirocumab.

Homozygous FHC is a genetic mutation that causes very high levels of low-density lipoprotein-cholesterol (LDL-C; "bad cholesterol") levels. This can cause early onset of atherosclerosis (build-up of fats, predominantly cholesterol in blood vessels). This often results in cardiovascular disease. Patients with FHC are usually treated with multiple cholesterol-lowering therapies such as statins, ezetimibe (Zetia), PCSK9 inhibitors, and lomitapide (Juxtapid). 

Alirocumab is an immunotherapy that has been shown to be effective in lowering LDL-C levels in patients with non-familial high cholesterol. To date, alirocumab has not been assessed for its effectiveness and safety in patients with FHC. 

The study was performed on 69 patients homozygous FHC. 24 of these patients were randomly assigned to a placebo. 45 patients were randomly assigned to alirocumab 150 mg every 2 weeks.. The initial treatment period was 12 weeks. At 12 weeks the patients who received a placebo were put onto alirocumab for a further 12 weeks.  

At week 12 the proportion of patients achieving over or equal to a 15% reduction in LDL-C was 61.9% in the alirocumab group and 12.5% in the placebo group. At week 12 the proportion of patients achieving a reduction of over or equal to 30% in LDL-C was 57.1% in the alirocumab group and 4.2% in the placebo group. 

Patients in the alirocumab group had an average LDL-C level of 295.0 mg/dl at the start of the trial. This was compared to 259.0 mg/dl in the placebo group. After 12 weeks, the levels of LDL-C decreased by 26.9% in the alirocumab group compared to an increase by 8.6% in the placebo group.

For patients who received a placebo for 12 weeks and then received alirocumab the reduction in LDL-C on average was 20.6%. For patients receiving alirocumab from the start to week 24, the average reduction in LDL-C was 30.7%.  

No serious side effects were reported in either treatment group during the trial period. There were 44.4% of the alirocumab group and 50% of patients in the placebo group who reported side effects related to treatment. These included headache, diarrhea, or upper respiratory infections.

The authors concluded that treatment with alirocumab resulted in a significant reduction in LDL-C levels and was well tolerated in patients with homozygous FHC.

This study was funded by Sanofi and Regeneron Pharmaceuticals Inc., the manufacturers of alirocumab.