Efficacy and safety of lomitapide in homozygous familial hypercholesterolaemia: the pan-European retrospective observational study

Abstract

Background Lomitapide is a lipid-lowering agent indicated as adjunct therapy for adult HoFH Objectives This study evaluated the medium-term effectiveness and safety of lomitapide in a large cohort of HoFH patients in Europe. Methods In a multicenter retrospective, observational study including 75 HoFH patients treated with lomitapide in a real-world clinical setting from 9 European countries, LDL-C changes, adverse events (AEs) as well as major adverse cardiovascular events (MACE) were assessed. Results After a median 19 months (IQR 11-41 months) of treatment with a mean dosage of 20 mg of lomitapide. LDL-C decreased by 60%, from baseline 280.5 mg/dL (191.8-405.0 mg/dl) to 121.6 mg/dl (61.0-190.5 mg/dl). At the last visit, 32.0% of patients achieved LDL-C < 100mg/dL and 18.7% <70 mg/dL. At baseline, 38 HoFH patients were receiving LDL apheresis (LA), but after initiation of lomitapide 36.8% of patients discontinued LA. During follow-up, lomitapide was permanently interrupted in 13% of patients. Gastrointestinal (GI) AEs occurred in 40% and liver transaminases increased (3-5 x ULN) in 13% of patients. Among patients with liver ultrasound evaluation (n = 45), a modest increase in hepatic steatosis was noted during treatment; however liver stiffness measured by elastography in 30 of them remained within the normal range. Among HoFH patients exposed to lomitapide for at least 2 years, MACE incident rate was 7.4 per 1000 person-years in the 2 years after as compared to 21.2 per 1000 person-years before treatment with lomitapide. Conclusions In this medium-term real-world experience, lomitapide proved to be very effective in reducing LDL-C in HoFH. GI AEs were common, but liver safety was reassuring with no sign of increased risk of liver fibrosis. A signal of cardiovascular protection was also observed.

Efficacy of Long-Term Treatment of Autosomal Recessive Hypercholesterolemia With Lomitapide: A Subanalysis of the Pan-European Lomitapide Study

“…This is a post hoc analysis of the Pan-European Lomitapide Study ( D’Erasmo et al, 2021b ) performed on a subgroup of patients diagnosed with ARH due to homozygous mutation in LDLRAP1 . The Pan-European Lomitapide Study was a multicenter, observational, and retrospective survey collecting data from all patients known to be receiving lomitapide in Europe in the context of usual clinical practice and without protocol-mandated procedures ( D’Erasmo et al, 2021b ). The protocol of the Pan-European Lomitapide Study has been reported in detail elsewhere ( D’Erasmo et al, 2021b ).…”

“…The Pan-European Lomitapide Study was a multicenter, observational, and retrospective survey collecting data from all patients known to be receiving lomitapide in Europe in the context of usual clinical practice and without protocol-mandated procedures ( D’Erasmo et al, 2021b ). The protocol of the Pan-European Lomitapide Study has been reported in detail elsewhere ( D’Erasmo et al, 2021b ). For a brief period, physicians were asked to retrospectively retrieve demographic and clinical information from medical records.…”

“…Although preliminary observations have indicated the efficacy of lomitapide in ARH, the size of this benefit and, more importantly, its long-term safety has been poorly investigated. We have recently completed a real-world survey, including hypercholesterolemic patients with biallelic pathogenic variants in LDLR and LDLRAP1 receiving lomitapide, in Europe ( D’Erasmo et al, 2021b ; D’Erasmo et al, 2021c ). This unique cohort provides the opportunity to perform a subanalysis of the carriers of homozygous mutations in LDLRAP1 to specifically evaluate the long-term LDL-lowering potential and safety of lomitapide in ARH.…”

Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics

“…In a real-world European study, lomitapide has been proved to be a very effective adjuvant drug to reduce LDL-C in HoFH patients for the longest follow-up period so far. 279 As lomitapide blocks MTP, it leads to impaired intestinal fat transport, making gastrointestinal symptoms as the most common adverse event in patients. 280 In terms of safety, lomitapide-related hepatic steatosis may not indirectly increase the risk of liver fibrosis, and the data suggest that lomitapide may reduce cardiovascular events in HoFH patients.…”

“… 280 In terms of safety, lomitapide-related hepatic steatosis may not indirectly increase the risk of liver fibrosis, and the data suggest that lomitapide may reduce cardiovascular events in HoFH patients. 279 …”