Lomitapide and Mipomersen—Inhibiting Microsomal Triglyceride Transfer Protein (MTP) and apoB100 Synthesis
Purpose of Review
The goal of this review is to evaluate the role of inhibiting the synthesis of lipoproteins when there is no or little residual LDL-receptor function as in patients with homozygous familial hypercholesterolaemia. Lomitapide is administered orally once a day while mipomersen is given by subcutaneous injection once a week. Lomitapide inhibits microsomal triglyceride transfer protein while mipomersen is an antisense oligonucleotide directed against apoB100.
The pivotal registration trials for lomitapide and mipomersen were published in 2013 and 2010, respectively. More recently published data from extension trials and cohort studies provides additional information on long-term safety and efficacy.
The mean LDL cholesterol reduction was 50% with lomitapide in its single-arm open-label registration trial. Mipomersen reduced LDL cholesterol by approximately 25% in its double-blind, placebo-controlled registration study. Both lomitapide and mipomersen therapy are associated with variable increases in hepatic fat content. The long-term safety of increased hepatic fat content in patients receiving these therapies is uncertain and requires further study. Both drugs may cause elevated transaminase in some patients, but no cases of severe liver injury have been reported. Lomitapide may also cause gastrointestinal discomfort and diarrhoea, especially if patients consume high-fat meals and patients are advised to follow a low-fat diet supplemented with essential fatty acids and fat-soluble vitamins. Mipomersen may cause injection-site and influenza-like reactions. The effect of lomitapide and mipomersen on cardiovascular outcomes has not been studied, but circumstantial evidence suggests that the LDL cholesterol lowering achieved with these two agents may reduce cardiovascular event rates.
KeywordsHomozygous Familial hypercholesterolaemia Microsomal triglyceride transfer protein Lomitapide Mipomersen
RDS is a recipient of a scholarship from the Conselho Nacional de Pesquisa e Desenvolvimento Tecnologico (CNPq) process no. 303734/2018-3.
Compliance with Ethical Standards
Conflict of Interest
Dirk J. Blom has received honoraria related to consulting, research and or speaker activities from: Aegerion, Akcea, Amgen, AstraZeneca, MSD, Novo-Nordisk, Sanofi, Regeneron. DJB chairs the LOWER registry steering committee. Frederick J. Raal has received research grants, honoraria or consulting fees for professional input and/or delivered lectures from Sanofi, Regeneron, Amgen and The Medicines Company. Raul D. Santos has received honoraria related to consulting, research and/or speaker activities from: Akcea, Amgen, AstraZeneca, Biolab, Esperion, Kowa, Merck, MSD, Novo-Nordisk, Sanofi, and Regeneron. A. David Marais has received a grant for studies from Sanofi and Aegerion.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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