Treatment with alirocumab was found to be associated with clinically meaningful long-term reductions in low-density lipoprotein cholesterol (LDL-C) in patients with autosomal dominant hypercholesterolemia (ADH) and elevated LDL-C treated with lipid-lowering therapy, according to a study published in the American Journal of Cardiology.

This was an open-label extension of a phase 2 randomized double-blind study in which the safety and efficacy of alirocumab, a fully human monoclonal antibody directed against proprotein convertase subtilisin/kexin type 9 (PCSK9), was evaluated in patients with ADH and PCSK9 gain-of-function mutations (GoFm) or apolipoprotein B (APOB) loss-of-function mutations (LoFm; identifier: NCT01604824).

All 23 participants who completed the 14-week double-blind period and 8-week follow-up period of the study were invited to enter this open-label extension study, during which they were given 150 mg alirocumab every 2 weeks from week 32 to 3 years. Of the 21 participants who opted to continue, 15 and 6 patients had PCSK9 GoFm and APOB LoFm, respectively. Mean duration of treatment exposure was 129 weeks (range, 82-180 weeks; median, 144 weeks), and only 1 participant (4.8%) did not attend the end-of-study follow-up visit.

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LDL-C levels decreased in both groups after 44 weeks of treatment compared with baseline (mean reduction: PCSK9 GoFm, 66.0±19.0%; APOB LoFm, 47.0±12.3%). The mean percent LDL-C reduction was greater in the PCSK9 GoFm vs APOB LoFm group at all time points (reduction at week 80: PCSK9 GoFm, 58.0±22.5%; APOB LoFm, 47.1±8.5%).

A total of 19 patients (90.5%) reported treatment-emergent adverse events, but no participant discontinued treatment as a consequence, and 3 participants (14.3%, all with PCSK9 GoFm) experienced treatment-emergent serious adverse events, with 2 cardiac disorders (unstable angina and myocardial infarction), 1 general disorder (chest pain), and 1 gastrointestinal disorder (salivary gland disorder), but none were considered to be related to alirocumab.

Study limitations include a small sample size and baseline differences in patient characteristics between participants with PCSK9 GoFm and those with APOB LoFm.

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“[T]he present study demonstrates that in patients with PCSK9 GoFm and APOB LoFm with elevated LDL-C levels despite maximally tolerated [lipid-lowering therapy], alirocumab 150 mg [every 2 weeks] resulted in long-term clinically meaningful LDL-C reductions, with no unexpected long-term safety concerns,” concluded the study authors.

Disclosure: This clinical trial was supported by Sanofi and Regeneron Pharmaceuticals, Inc. Please see the original reference for a full list of authors’ disclosures.


Krempf M, Hopkins PN, Bruckert E, Lee S, Donahue S. Efficacy and safety of alirocumab in patients with autosomal dominant hypercholesterolemia associated with proprotein convertase subtilisin/kexin type 9 gain-of-function or apolipoprotein B loss-of-function mutations [published online December 27, 2019]. Am J Cardiol. doi: 10.1016/j.amjcard.2019.12.028