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Review
. 2025 Jan 3;27(1):22.
doi: 10.1007/s11883-024-01269-5.

Homozygous Familial Hypercholesterolemia Treatment: New Developments

Dirk J Blom  1 , A David Marais  2 , Frederick J Raal  3
Affiliations
Review

Homozygous Familial Hypercholesterolemia Treatment: New Developments

Dirk J Blom et al. Curr Atheroscler Rep. .

Abstract

Purpose of review: Homozygous familial hypercholesterolaemia (HoFH) is characterized by marked elevation of low-density lipoprotein cholesterol (LDLC) and premature atherosclerotic cardiovascular disease. This is a review of novel pharmacological therapies to lower LDLC in patients with HoFH.

Recent findings: Novel therapies can be broadly divided by whether their efficacy is dependent or independent of residual low-density lipoprotein receptor (LDLR) function. Novel LDLR dependent therapies that reduce proprotein subtilisin kexin type 9 levels include monoclonal antibodies (alirocumab and evolocumab) and a small inhibitory RNA (inclisiran). LDLC reductions are highly variable and depend on residual LDLR function. Microsomal triglyceride inhibitors (lomitapide) and therapies that reduce angiopoietin like factor 3 (evinacumab and zodasiran) both reduce LDLC by approximately 50%, irrespective of residual LDLR function. Most patients with HoFH require multiple therapies to achieve LDLC targets. Better LDLC control with LDLR independent therapies is likely to improve the outlook for patients with HoFH while at the same time reducing the need for other therapies such as apheresis or hepatic transplantation.

Keywords: Angiopoietin like factor 3; Gene editing; Homozygous familial hypercholesterolemia; Microsomal; Proprotein convertase subtilisin kexin type 3; Triglyceride transfer protein.

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Conflict of interest statement

Declarations. Competing Interests: DJ Blom DB reports personal fees from Amgen, Amryt, MSD, Novartis, Sanofi and Servier and outside the submitted work. A David Marais ADM reports no personal fees from the companies producing the agents discussed but had support for the performance of the study of atorvastatin and lomitapide by Warner Lambert Parke Davis and Aegerion, respectively. FJ Raal FJR reports personal fees from LIB Therapeutics, Amgen, Sanofi, Regeneron Pharmaceuticals, Inc., and Novartis outside the submitted work. Human and Animal Rights and Informed Consent: All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

References

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