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

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Study designLLT, lipid-lowering therapy; MTD, maximum tolerated dose.
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Figure 1: Study designLLT, lipid-lowering therapy; MTD, maximum tolerated dose.

Mentions: In this phase 3, single-arm, open-label study, adult patients with HoFH added lomitapide to their maximally tolerated, stable, LLT. After initial screening, including informed consent (during Weeks −12 to −6), the study progressed in three phases (Fig. 1): −6–0 weeks, pre-treatment run-in during which both diet and other LLTs were stabilized; 0–26 weeks, dose-escalation and efficacy measures; and > 26–56 weeks, safety measures. At the conclusion of this trial, patients had the option of continuing in a long-term extension trial.


Efficacy and Safety of Lomitapide in Japanese Patients with Homozygous Familial Hypercholesterolemia
Study designLLT, lipid-lowering therapy; MTD, maximum tolerated dose.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5392478&req=5

Figure 1: Study designLLT, lipid-lowering therapy; MTD, maximum tolerated dose.
Mentions: In this phase 3, single-arm, open-label study, adult patients with HoFH added lomitapide to their maximally tolerated, stable, LLT. After initial screening, including informed consent (during Weeks −12 to −6), the study progressed in three phases (Fig. 1): −6–0 weeks, pre-treatment run-in during which both diet and other LLTs were stabilized; 0–26 weeks, dose-escalation and efficacy measures; and > 26–56 weeks, safety measures. At the conclusion of this trial, patients had the option of continuing in a long-term extension trial.

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.