Long-term treatment of homozygous familial hypercholesterolemia with lomitapide: 11 years of safety and effectiveness findings from the Lomitapide Observational Worldwide Evaluation Registry.

BACKGROUND: Lomitapide is an oral microsomal triglyceride transfer protein inhibitor approved for homozygous familial hypercholesterolemia (HoFH). OBJECTIVE: Evaluate data from the Lomitapide Observational Worldwide Evaluation Registry (LOWER; NCT02135705). METHODS: LOWER is a global, prospective observational registry initiated in March 2014 to evaluate the real-world effectiveness and safety of lomitapide in patients with HoFH. RESULTS: A total of 246 individuals were enrolled (43.5% male; mean age 50.3 years, SD 15.3; range 18-83). Mean lomitapide daily dose was 12.1 mg (SD 8.7; range 1.4-50.0). Patients received lomitapide for an average of 45.6 months (SD 38.4; range 0.3-142.1). Baseline mean low-density lipoprotein cholesterol (LDL-C) was 241.1 mg/dL (SD 109.1; range 71-672). Following treatment initiation, 86.8% of patients on lomitapide achieved ≥50% LDL-C reduction at some time point (72.2% in the full analysis set [FAS]). In the FAS, 74.3% achieved LDL-C <100 mg/dL, 51.0% <70 mg/dL, and 38.4% achieved <55 mg/dL LDL-C at any time. Adverse events were mostly gastrointestinal in nature (n = 111; 45.3%). Hepatic events of special interest (ESIs) were reported in 21.6%, and gastrointestinal ESIs occurred in 13.9% of patients. Major adverse cardiovascular events (MACE) occurred in 15.9% of patients, and no MACE were attributed to lomitapide. Exposure-adjusted MACE incidence was 2.8 events per 100-person years on lomitapide, vs 4.3 after lomitapide discontinuation. CONCLUSION: LOWER supports lomitapide's long-term effectiveness and safety for up to 11 years, enabling substantial LDL-C reductions and treatment goal achievement in HoFH with a manageable safety profile. Tentative evidence of reduced MACE during lomitapide treatment warrants further investigation.