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.
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.
Authors: Samuel S Gidding; Mary Ann Champagne; Sarah D de Ferranti; Joep Defesche; Matthew K Ito; Joshua W Knowles; Brian McCrindle; Frederick Raal; Daniel Rader; Raul D Santos; Maria Lopes-Virella; Gerald F Watts; Anthony S Wierzbicki Journal: Circulation Date: 2015-10-28 Impact factor: 29.690
Authors: C Stefanutti; D J Blom; M R Averna; E A Meagher; H dT Theron; A D Marais; R A Hegele; C R Sirtori; P K Shah; D Gaudet; G B Vigna; B S Sachais; S Di Giacomo; A M E du Plessis; L T Bloedon; J Balser; D J Rader; M Cuchel Journal: Atherosclerosis Date: 2015-03-14 Impact factor: 5.162
Authors: Marina Cuchel; Emma A Meagher; Hendrik du Toit Theron; Dirk J Blom; A David Marais; Robert A Hegele; Maurizio R Averna; Cesare R Sirtori; Prediman K Shah; Daniel Gaudet; Claudia Stefanutti; Giovanni B Vigna; Anna M E Du Plessis; Kathleen J Propert; William J Sasiela; LeAnne T Bloedon; Daniel J Rader Journal: Lancet Date: 2012-11-02 Impact factor: 79.321
Authors: Frederick J Raal; Narimon Honarpour; Dirk J Blom; G Kees Hovingh; Feng Xu; Rob Scott; Scott M Wasserman; Evan A Stein Journal: Lancet Date: 2014-10-01 Impact factor: 79.321
Authors: Lili Wang; Ilayaraja Muthuramu; Suryanarayan Somanathan; Hong Zhang; Peter Bell; Zhenning He; Hongwei Yu; Yanqing Zhu; Anna P Tretiakova; James M Wilson Journal: Mol Ther Methods Clin Dev Date: 2021-05-05 Impact factor: 6.698