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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.


Percentage change in LDL-C during treatment (full analysis set)LDL-C, low-density lipoprotein cholesterol; LOCF, last observation carried forward
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Figure 3: Percentage change in LDL-C during treatment (full analysis set)LDL-C, low-density lipoprotein cholesterol; LOCF, last observation carried forward

Mentions: There was a highly significant reduction in LDL-C from baseline to Week 26 (Fig. 2, Table 2). Mean LDL-C reduced by 42% from 199 mg/dL (95% CI: 149–250) at baseline to 118 mg/dL (95% CI: 70–166) at Week 26. A decrease in mean LDL-C (19%) occurred as early as the first 2 weeks on treatment, with continued reduction occurring steadily over time thereafter (Fig. 3). The reduction in LDL-C was significant across patients with and without apheresis (Fig. 2). At Week 26, a ≥ 50% reduction in LDL-C from baseline was achieved by five out of nine patients which was maintained through to Week 56. During the efficacy phase, six of the nine patients achieved the target LDL-C level of < 100 mg/dL recommended for patients with HoFH; of these six patients, three achieved levels < 70 mg/dL by Week 26 and an additional patient achieved this by Week 56.


Efficacy and Safety of Lomitapide in Japanese Patients with Homozygous Familial Hypercholesterolemia
Percentage change in LDL-C during treatment (full analysis set)LDL-C, low-density lipoprotein cholesterol; LOCF, last observation carried forward
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Percentage change in LDL-C during treatment (full analysis set)LDL-C, low-density lipoprotein cholesterol; LOCF, last observation carried forward
Mentions: There was a highly significant reduction in LDL-C from baseline to Week 26 (Fig. 2, Table 2). Mean LDL-C reduced by 42% from 199 mg/dL (95% CI: 149–250) at baseline to 118 mg/dL (95% CI: 70–166) at Week 26. A decrease in mean LDL-C (19%) occurred as early as the first 2 weeks on treatment, with continued reduction occurring steadily over time thereafter (Fig. 3). The reduction in LDL-C was significant across patients with and without apheresis (Fig. 2). At Week 26, a ≥ 50% reduction in LDL-C from baseline was achieved by five out of nine patients which was maintained through to Week 56. During the efficacy phase, six of the nine patients achieved the target LDL-C level of < 100 mg/dL recommended for patients with HoFH; of these six patients, three achieved levels < 70 mg/dL by Week 26 and an additional patient achieved this by Week 56.

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 &lt; 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 &lt; 0.0001) at 26 weeks, from 199 mg/dL (95% CI: 149&ndash;250) at baseline to 118 mg/dL (95% CI: 70&ndash;166). A 50% reduction in LDL-C and LDL-C &lt; 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.