Long-term clinical results of microsomal triglyceride transfer protein inhibitor use in a patient with homozygous familial hypercholesterolemia

Raper, Anna; Kolansky, Daniel M.; Sachais, Bruce S.; Meagher, Emma A.; Baer, Amanda; Cuchel, Marina

doi:10.1016/j.jacl.2014.08.005

Cited by 25 publications

(22 citation statements)

References 9 publications

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“…Attempts were made to reduce the dose to 40 mg/day, but the patient experienced rebound in LDL-C characteristic of hypo-responsiveness. However, the success in this patient lies in that she was able to achieve LDL-C levels of just 50 mg/dL with discontinuation of LA and only a transient increase in LFTs at the time of the re-escalation in lomitapide dose [48].…”

Section: Real-world Evidencementioning

confidence: 88%

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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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Section: Real-world Evidencementioning

confidence: 88%

“…None of these variants was present in the hypo-responders [47]. An example of hypo-responsiveness was evident in a 2015 case from a Hispanic female [48]. Raper et al continued to treat a HoFH patient who had been on the maximum 60 mg/day dose of lomitapide in the pivotal phase 3 trial.…”

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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“…Careful attention to diet and safety monitoring (liver function and gastrointestinal complains) is necessary when using this agent 7) . Raper et al 8) reported a HoFH patient treated for 5 years with lomitapide who achieved a marked reduction in LDL-C concentration, reaching the desirable target level of 70 mg/dl. Cuchel et al 9) reported overall reductions in LDL-C from baseline by 50% with the median dose of lomitapide of 40 mg/daily.…”

Section: Resultsmentioning

confidence: 99%

MTP Gene Variants and Response to Lomitapide in Patients with Homozygous Familial Hypercholesterolemia

Kolovou

Papadopoulou

et al. 2016

JAT

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“…MTTP mediates lipidation of apolipoprotein B, which is a crucial step in the formation of many lipoprotein species that range from intestinally-derived chylomicrons to hepatic VLDL and LDL particles. Since this effect is not mediated by the LDL-receptor pathway, lomitapide also offers a unique treatment option for familial hypercholesterolemia homozygotes with little or no residual receptor activity (Raper et al 2015). Given its mechanism of action, it is not surprising that lomitapide administration also results in a significant reduction in plasma TG levels, which may reach two thirds of the baseline values.…”

Section: Novel Therapies and Their Impact Of Tg Levelsmentioning

confidence: 99%

Treatment of Hypertriglyceridemia: a Review of Current Options

Vráblík

Češka²

2015

Physiol Res

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Hypertriglyceridemia is an important marker of increased levels of highly atherogenic remnant-like particles. The importance of lowering plasma levels of triglycerides (TG) has been called into question many times, but currently it is considered an integral part of residual cardiovascular risk reduction strategies. Lifestyle changes (improved diet and increased physical activity) are effective TG lowering measures. Pharmacological treatment usually starts with statins, although associated TG reductions are typically modest. Fibrates are currently the drugs of choice for hyperTG, frequently in combination with statins. Niacin and omega-3 fatty acids improve control of triglyceride levels when the above measures are inadequately effective. Some novel therapies including anti-sense oligonucleotides and inhibitors of microsomal triglyceride transfer protein have shown significant TG lowering efficacy. The current approach to the management of hypertriglyceridemia is based on lifestyle changes and, usually, drug combinations (statin and fibrate and/or omega-3 fatty acids or niacin).

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Long-term clinical results of microsomal triglyceride transfer protein inhibitor use in a patient with homozygous familial hypercholesterolemia

Cited by 25 publications

References 9 publications

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

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

MTP Gene Variants and Response to Lomitapide in Patients with Homozygous Familial Hypercholesterolemia

Treatment of Hypertriglyceridemia: a Review of Current Options

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