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Review
. 2021 Sep 1;23(11):65.
doi: 10.1007/s11883-021-00967-8.

Rare Treatments for Rare Dyslipidemias: New Perspectives in the Treatment of Homozygous Familial Hypercholesterolemia (HoFH) and Familial Chylomicronemia Syndrome (FCS)

Laura D'Erasmo  1 , Simone Bini  1 , Marcello Arca  2
Affiliations
Review

Rare Treatments for Rare Dyslipidemias: New Perspectives in the Treatment of Homozygous Familial Hypercholesterolemia (HoFH) and Familial Chylomicronemia Syndrome (FCS)

Laura D'Erasmo et al. Curr Atheroscler Rep. .

Abstract

This review aims to summarize the most recent published literature concerning lomitapide and volanesorsen that are approved for the use in HoFH and FCS patients, respectively. Moreover, it will briefly revise the published evidence on novel, non-approved treatments that are under evaluation for the management of these rare forms of dyslipidemias RECENT FINDINGS: The definition of rare dyslipidemias identifies a large number of severe disorders of lipid metabolism of genetic origin. Among them were homozygous familial hypercholesterolemia (HoFH) (OMIM #143890) and familial chylomicronemia syndrome (FCS) (OMIM #238600), which are characterized by a markedly impaired cholesterol- and triglyceride-containing lipoproteins metabolism. They are being particularly associated with poor health outcomes and quality of life. Considering the severity of these diseases, common lipid-lowering drugs are often ineffective or do not allow to achieve the recommended lipid targets to prevent the development of complications. Nowadays, several new drugs have been found to effectively treat HoFH and FCS with an acceptable safety profile. Treating patients with HoFH and FCS remains very challenging. However, novel treatment options are emerging and might be considered in addition to conventional therapy for managing these diseases. These novel drugs will possibly change the natural history of these two rare and life-threatening diseases.

Keywords: Drugs; Familial chylomicronemia syndrome; Homozygous familial hypercholesterolemia; Lomitapide; Volanesorsen.

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Conflict of interest statement

Laura D’Erasmo has received personal fees for public speaking, consultancy, or grant support from Amryt Pharmaceuticals, Akcea Therapeutics, Pfizer, Amgen, and Sanofi.

Marcello Arca has received research grant support from Amryt Pharmaceutical, Amgen, IONIS, Akcea Therapeutics, Pfizer, and Sanofi; has served as a consultant for Amgen, Aegerion, Akcea Therapeutics, Regeneron, Sanofi, and Alfasigma; and received lecturing fees from Amgen, Amryt Pharmaceutical, Pfizer, Sanofi, and AlfaSigma.

Simone Bini declares no competing interests.

Figures

Fig. 1.
Fig. 1.
Molecular effects of novel lipid-lowering drugs. Legend: molecular and cellular effects of novel lipid-lowering drugs. Lomitapide inhibits MTP protein, thus blocking lipoprotein lipidation in endoplasmic reticulum. Vupanorsen and Gal-NAc apoCIII inhibitor are Gal-NAc-conjugated ASOs; therefore, they are specifically internalized by the liver through the asialoglycoprotein receptor, and they prevent ANGPTL3 and apoCIII mRNA to be transcripted. Inclisiran is a Gal-NAc-conjugated siRNA, it is also internalized through the ASGPR receptor, and it mediates PCSK9 mRNA degradation. Evinacumab is a monoclonal antibody; it is directed to the secreted ANGPTL3 protein. Volanesorsen is a non-conjugated ASO; therefore, it is not liver specific. It prevents apoCIII mRNA to be translated
See this image and copyright information in PMC

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