Evaluation of the Real-World Effectiveness and Safety of Lomitapide in the Management of HoFH: The European Experience Study

Abstract

Lead Author's Financial Disclosures L.D. has received consulting fees for Amryt. Study Funding Amryt Pharma. Background/Synopsis Homozygous familial hypercholesterolemia (HoFH) is characterized by severely elevated low-density lipoprotein-cholesterol (LDL-C) associated with extreme cardiovascular risk. Lomitapide is a lipid-lowering agent indicated as adjunct therapy for HoFH patients. This study aimed at evaluating the real-world long-term effectiveness and safety of lomitapide in the management of HoFH. Objective/Purpose The present analysis provides real world evidence on the effectiveness and safety of lomitapide in 75 HoFH patients treated in Europe for up to 9 years. Methods This multicenter European retrospective, observational cohort study collected clinical data from HoFH patients treated with lomitapide. LDL-C reduction versus baseline at 108 months was calculated. Adverse events (AEs), including major adverse cardiovascular events (MACE) and liver imaging were evaluated as safety outcomes. The study was conducted by the Italian and European Working Group on Lomitapide in HoFH. Results 75 HoFH patients from 9 countries were assessed (median age 44 yrs. [interquartile range; IQR 30.0-55.2], 60% with a previous major adverse cardiovascular event (MACE). Median baseline LDL-C was 280.5 mg/dL (IQR 191.8-405.0). At 108 months, median LDL-C decreased by 60% to 121.6 mg/dl (61.0-190.5). At baseline 38 (50.7%) patients received apheresis, after 108 months 14 (36.8%) discontinued apheresis, 32.0% achieved LDL-C ≤100mg/dL and 18.7% ≤70mg/dL. Incident MACE decreased from 28.8% within 2 yrs before lomitapide treatment, to 5.3% up to 2 yrs after treatment. At 3 months AEs were experienced by 33 (51.6%) patients, most frequently gastrointestinal, though these decreased from 37.5% to 6.1% at 24 months. Ten patients stopped treatment with lomitapide, 6 due to AEs. Liver tests did not change significantly during follow-up. In the subset of patients where ultrasound liver imaging data was available (n=45), a modest increase in hepatic steatosis was observed (at baseline 37.3% absent, 17.3% mild, 5.3% moderate vs 14.7% absent, 18.7% mild and 17.3% moderate at last visit) but hepatic stiffness measured by Fibroscan remained within the normal range, 3.4+/-2.3 kPa at baseline (n=15) vs 4.6+/-1.3 kPa at last visit (n=24). Conclusions Real-world experience in a large cohort of HoFH patients with long-term follow-up data showed that lomitapide is an effective treatment for reducing LDL-C in HoFH with an improved tolerability profile versus the phase 3 study. Liver imaging demonstrated a modest increase in hepatic fat but hepatic stiffness remained in the normal range. Additional data are needed to determine the potential impact of LDL-C reduction with lomitapide on major adverse cardiovascular events in HoFH. L.D. has received consulting fees for Amryt.