Abstract:
OBJECTIVE : Lomitapide (a microsomal triglyceride transfer protein inhibitor) is an adjunctive treatment
for homozygous familial hypercholesterolaemia (HoFH), a rare genetic condition characterised by
elevated low-density lipoprotein-cholesterol (LDL-C), and premature, severe, accelerated atherosclerosis.
Standard of care for HoFH includes lipid-lowering drugs and lipoprotein apheresis.We conducted a posthoc
analysis using data from a Phase 3 study to assess whether concomitant apheresis affected the lipidlowering
efficacy of lomitapide.
METHODS : Existing lipid-lowering therapy, including apheresis, was to remain stable from Week 6 to
Week 26. Lomitapide dose was escalated on the basis of individual safety/tolerability from 5 mg to 60 mg
a day (maximum). The primary endpoint was mean percent change in LDL-C from baseline to Week 26
(efficacy phase), after which patients remained on lomitapide through Week 78 for safety assessment
and further evaluation of efficacy. During this latter period, apheresis could be adjusted.We analysed the
impact of apheresis on LDL-C reductions in patients receiving lomitapide.
RESULTS : Of the 29 patients that entered the efficacy phase, 18 (62%) were receiving apheresis at baseline.
Twenty-three patients (13 receiving apheresis) completed the Week 26 evaluation. Of the six patients
who discontinued in the first 26 weeks, five were receiving apheresis. There were no significant differences
in percent change from baseline of LDL-C at Week 26 in patients treated ( 48%) and not treated
( 55%) with apheresis (p ¼ 0.545). Changes in Lp(a) levels were modest and not different between
groups (p ¼ 0.436).
CONCLUSION : The LDL-C lowering efficacy of lomitapide is unaffected by lipoprotein apheresis.
