Pharmacokinetics and Pharmacodynamics of Lomitapide in Japanese Subjects

Täubel, Jörg; Sumeray, Mark; Lorch, Ulrike; McLean, A. E. M.

doi:10.5551/jat.30452

Cited by 8 publications

(3 citation statements)

References 28 publications

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“…The microsomal triglyceride transfer protein inhibitor, lomitapide, is an orally administered agent and the mechanism underlying its LDL-C lowering effect is independent of LDL receptor activation. However, abdominal pain, diarrhea, liver dysfunction and fatty liver have been reported as adverse effects of this drug and although it has been already approved for use in adult patients with HoFH in Japan, it is not approved for childhood HoFH at present 40 , 41 ) .…”

Section: Treatment Of Pediatric Fhmentioning

confidence: 99%

Guidance for Pediatric Familial Hypercholesterolemia 2017

Harada‐Shiba

Ohta²,

Ohtake

et al. 2018

J Atheroscler Thromb

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This paper describes consensus statement by Joint Working Group by Japan Pediatric Society and Japan Atherosclerosis Society for Making Guidance of Pediatric Familial Hypercholesterolemia (FH) in order to improve prognosis of FH.FH is a common genetic disease caused by mutations in genes related to low density lipoprotein (LDL) receptor pathway. Because patients with FH have high LDL cholesterol (LDL-C) levels from the birth, atherosclerosis begins and develops during childhood which determines the prognosis. Therefore, in order to reduce their lifetime risk for cardiovascular disease, patients with FH need to be diagnosed as early as possible and appropriate treatment should be started.Diagnosis of pediatric heterozygous FH patients is made by LDL-C ≥ 140 mg/dL, and family history of FH or premature CAD. When the diagnosis is made, they need to improve their lifestyle including diet and exercise which sometimes are not enough to reduce LDL-C levels. For pediatric FH aged ≥ 10 years, pharmacotherapy needs to be considered if the LDL-C level is persistently above 180 mg/dL. Statins are the first line drugs starting from the lowest dose and are increased if necessary. The target LDL-C level should ideally be < 140 mg/dL. Assessment of atherosclerosis is mainly performed by noninvasive methods such as ultrasound.For homozygous FH patients, the diagnosis is made by existence of skin xanthomas or tendon xanthomas from infancy, and untreated LDL-C levels are approximately twice those of heterozygous FH parents. The responsiveness to pharmacotherapy should be ascertained promptly and if the effect of treatment is not enough, LDL apheresis needs to be immediately initiated.

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Section: Treatment Of Pediatric Fhmentioning

confidence: 99%

Guidance for Pediatric Familial Hypercholesterolemia 2017

Harada‐Shiba

Ohta²,

Ohtake

et al. 2018

J Atheroscler Thromb

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“…17, 22–24) . The results of the current study were also in line with the real-world results reported from a global observational registry prospectively assessing the long-term safety and effectiveness of lomitapide in real-life clinical practice (the LOWER study).…”

Section: Discussionmentioning

confidence: 99%

“…This dose is supported by previously reported pharmacokinetic results in Japanese patients. 24) . MTD was defined as the highest dose during Weeks 0–26 that did not result in unacceptable adverse events (AEs), including elevated liver function tests (LFTs).…”

Section: Methodsmentioning

confidence: 99%

Efficacy and Safety of Lomitapide in Japanese Patients with Homozygous Familial Hypercholesterolemia

Harada‐Shiba

Ikewaki

Nohara

et al. 2017

J Atheroscler Thromb

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Aim: There is an unmet need in Japan for more optimal lipid-lowering therapy (LLT) for patients with homozygous familial hypercholesterolemia (HoFH) who respond inadequately to available drug therapies and/or apheresis, to achieve goals of low-density lipoprotein cholesterol (LDL-C) reduction by 50% or to < 100 mg/dL.Methods: In this study, Japanese patients with HoFH on stable LLT and diet were treated with lomitapide, initiated at 5 mg/day and escalated to maximum tolerated dose (up to 60 mg/day) over 14 weeks. The primary efficacy endpoint was mean percentage change from baseline to Week 26 in LDL-C. Secondary endpoints included changes in other lipid parameters and safety throughout the 56-week study (including follow-up).Results: Nine patients entered the efficacy phase of the study and, of these, eight completed 56 weeks. Mean LDL-C was reduced by 42% (p < 0.0001) at 26 weeks, from 199 mg/dL (95% CI: 149–250) at baseline to 118 mg/dL (95% CI: 70–166). A 50% reduction in LDL-C and LDL-C < 100 mg/dL was achieved by five and six of nine patients, respectively, at 26 weeks. After 56 weeks, LDL-C was reduced by 38% (p = 0.0032) from baseline. Significant reductions in non-HDL-C, VLDL-C, triglycerides, and apolipoprotein B were also reported at Week 26. There were no new safety signals and, similar to previous studies, gastrointestinal adverse events were the most common adverse events.Conclusion: Lomitapide, added to ongoing treatment with other LLTs, was effective in rapidly and significantly reducing the levels of LDL-C and other atherogenic apolipoprotein B-containing lipoproteins in adult Japanese patients with HoFH.

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