Abstract 10818: Lomitapide Observational Worldwide Evaluation Registry (LOWER): One-Year Data

Abstract

Introduction: Lomitapide is a microsomal triglyceride transfer protein inhibitor indicated as an adjunctive therapy for adults with homozygous familial hypercholesterolemia (HoFH). LOWER is a global, long-term, prospective, observational registry of the long-term safety and effectiveness of lomitapide in clinical practice. At least 300 adult HoFH patients will be followed for a minimum of 10 years. Enrollment opened in March 2014 for adult HoFH patients with less than 15 months of lomitapide exposure. We present data from the first year of the registry. Results: As of March 1, 2015, 84 patients with mean age 55.4 (SD 11.5) years, were enrolled in LOWER; 6 (7%) have since discontinued. Exposure duration was up to 26 months, with 60% of patients receiving the drug for ≥12 months. Lomitapide dose ranged from 5 to 40 mg; dose increased over time to a median of 13.0 mg (mean 14.4 mg) after 2 years’ exposure. Mean LDL-C at baseline was 216.3 (SD 76.9) mg/dL which decreased by 42% at Month 4 and was maintained throughout the reporting period. Fifty-one (61%) and 30 (36%) respectively achieved an LDL-C value <100 mg/dL or <70 mg/dL, at least once while receiving lomitapide. Events of special interest (ESI) include: 1 major adverse cardiovascular event (MACE) resulting in death; 11 hepatic events; and 6 gastrointestinal events. No tumors, pregnancies, or coagulopathy events were reported. Elevated aminotransferase levels ≥3x upper limit of normal (ULN) were observed in 16 patients (20%); 4 of these patients experienced elevations of ≥5x - <10x ULN. No cases of Hy’s Law were recorded. Diarrhea was the most common adverse event (AE), experienced by 24% of patients, and the only AE reported by >10% of patients. Serious AEs occurred in 6 (7%) patients. Eight (10%) patients discontinued lomitapide because of an AE. Conclusions: Data from the first year of the LOWER registry demonstrate both safety and efficacy that are consistent with the product labeling. There were no new safety signals. Discontinuations because of aminotransferase or gastrointestinal ESIs were low. Future data from LOWER will provide further information about the real-world, long-term safety and effectiveness of lomitapide in HoFH.