&lt;p&gt;Lomitapide: a review of its clinical use, efficacy, and tolerability&lt;/p&gt;

Alonso, Rodrigo; Cuevas, Ada; Mata, Pedro

doi:10.2147/ce.s174169

Cited by 54 publications

(36 citation statements)

References 38 publications

(46 reference statements)

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“…Lomitapide, a microsomal triglyceride transfer protein (MTP) inhibitor, is licensed for treatment of homozygous familial hypercholesterolaemia (HoFH) but is known to cause hepatic dysfunction. 91 One patient with FCS was treated with lomitapide for 13 years achieving a 75% reduction in TGs, a reduction in pancreatitis admissions but unfortunately developed hepatic fibrosis. 92 A different approach has been to inhibit intra-cellular triglyceride synthesis from diglyceride precursors which is a feature of CM and VLDL production.…”

Section: Therapeutic Competitorsmentioning

confidence: 99%

<p>Volanesorsen in the Treatment of Familial Chylomicronemia Syndrome or Hypertriglyceridaemia: Design, Development and Place in Therapy</p>

Esan¹,

Wierzbicki²

2020

DDDT

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Severe hypertriglyceridaemia is associated with pancreatitis and chronic pancreatitis-induced diabetes. Familial chylomicronaemia syndrome (FCS) is a rare autosomal recessive disorder of lipid metabolism characterised by high levels of triglycerides (TGs) due to failure of chylomicron clearance. It causes repeated episodes of severe abdominal pain, fatigue and attacks of acute pancreatitis. There are few current options for its long-term management. The only universal long-term therapy is restriction of total dietary fat intake to <10-15% of daily calories (15 to 20g per day). Many patients have been treated with fibrates and statins with a variable response, but many remain susceptible to pancreatitis. Other genetic syndromes associated with hypertriglyceridaemia include familial partial lipodystrophy (FPLD). Targeting apolipoprotein C3 (apoC3) offers the ability to increase clearance of chylomicrons and other triglyceride-rich lipoproteins. Volanesorsen is an antisense oligonucleotide (ASO) inhibitor of apoC3, which reduces TG levels by 70–80% which has been shown also to reduce rates of pancreatitis and improve well-being in FCS and reduce TGs and improve insulin resistance in FPLD. It is now undergoing licensing and payer reviews. Further developments of antisense technology including small interfering RNA therapy to apoC3 as well as other approaches to modulating triglycerides are in development for this rare disorder.

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Section: Therapeutic Competitorsmentioning

confidence: 99%

<p>Volanesorsen in the Treatment of Familial Chylomicronemia Syndrome or Hypertriglyceridaemia: Design, Development and Place in Therapy</p>

Esan¹,

Wierzbicki²

2020

DDDT

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“…Not all patients can benefit from low doses of lomitapide. It is known that there can be variability in response to the drug [46], and it is possible that this is driven by phenotypic variability in MTP. This notion is borne out by data from a study of four HoFH cases from Greece treated with lomitapide in which two patients were characterized as "hyper-responders" (LDL-C reductions > 50%) and two as "hypo-responders" (LDL-C reductions < 50%).…”

Section: Real-world Evidencementioning

confidence: 99%

Lomitapide–a Microsomal Triglyceride Transfer Protein Inhibitor for Homozygous Familial Hypercholesterolemia

Stefanutti

2020

Curr Atheroscler Rep

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Purpose of Review Homozygous familial hypercholesterolemia (HoFH) is a rare, genetic condition characterized by high levels of Low density lipoprotein cholesterol (LDL-C); overt, early-onset atherosclerotic cardiovascular disease (ASCVD); and premature cardiovascular events and mortality. Lomitapide is a first-in-class microsomal triglyceride transfer protein inhibitor for the treatment of HoFH. This review provides an update on data emerging from real-world studies of lomitapide following on from its pivotal phase 3 clinical trial in HoFH. Recent Findings Recent registry data have confirmed that HoFH is characterized by delayed diagnosis, with many patients not receiving effective therapy until they are approaching the age when major adverse cardiovascular events may occur. Data from case series of varying sizes, and from a 163-patient registry of HoFH patients receiving lomitapide, have demonstrated that lomitapide doses are lower and adverse events less severe than in the phase 3 study. Lomitapide enables many patients to reach European Atherosclerosis Society LDL-C targets. Some patients are able to reduce frequency of lipoprotein apheresis or, in some cases, stop the procedure altogether-unless there is significant elevation of lipoprotein (a). Modelling analyses based on historical and clinical trial data indicate that lomitapide has the potential to improve cardiovascular outcomes and survival in HoFH. Summary Real-world clinical experience with lomitapide has shown the drug to be effective with manageable, less marked adverse events than in formal clinical studies. Event modelling data suggest a survival benefit with lomitapide in HoFH.

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“…Lomitapide is an inhibitor of the microsomal triglyceride transfer protein, which can reduce LDL-C levels by around 40% in HoFH patients undergoing treatment with statins, either with or without LDL apheresis. However, side effects including gastrointestinal symptoms and the production of liver fat, and lomitapide is not licensed by the China Food and Drug Administration (11). However, because most drugs increase the LDLR level by upregulating LDLR expression, structural defects of the LDLR limit the efficacy of those drugs because they do not alter receptor function (12).…”

Section: Discussionmentioning

confidence: 99%

Case Report: Cardiac Surgery and Combined Lipid-Lowering Drug Therapy for Homozygous Familial Hypercholesterolemia

Gao

Huang

et al. 2020

Front. Pediatr.

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Homozygous familial hypercholesterolemia (HoFH) is a rare, autosomal dominant, hereditary, metabolic disease. HoFH patients exhibit severe coronary stenosis and valvular disease, which may result in sudden death, even during adolescence. The challenges faced during surgery and the poor curative effect of conventional lipid-lowering therapy create a treatment bottleneck. We report a rare case of HoFH in a 12-years-old boy with acute myocardial infarction, severe mitral insufficiency, and moderate aortic insufficiency. Coronary artery bypass grafting and valvuloplasty resulted in improved heart function. Postoperative combined lipid-lowering drug therapy was able to reduce low-density lipoprotein cholesterol level from 15.37 mm/L to 6.41 mmol/L. Thus, the combination of medical and surgical treatment was considered effective and can be used to inform treatment guidelines for HoFH with severe complications.

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<p>Lomitapide: a review of its clinical use, efficacy, and tolerability</p>

Cited by 54 publications

References 38 publications

<p>Volanesorsen in the Treatment of Familial Chylomicronemia Syndrome or Hypertriglyceridaemia: Design, Development and Place in Therapy</p>

<p>Volanesorsen in the Treatment of Familial Chylomicronemia Syndrome or Hypertriglyceridaemia: Design, Development and Place in Therapy</p>

Lomitapide–a Microsomal Triglyceride Transfer Protein Inhibitor for Homozygous Familial Hypercholesterolemia

Case Report: Cardiac Surgery and Combined Lipid-Lowering Drug Therapy for Homozygous Familial Hypercholesterolemia

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