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.

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

“[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.

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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

This article originally appeared on The Cardiology Advisor