LOWER, a registry of lomitapide-treated patients with homozygous familial hypercholesterolemia: Rationale and design

- Homozygous familial hypercholesterolemia (HoFH) is a rare hereditary condition
- Lomitapide is a novel agent approved as adjunctive therapy for HoFH
- Its long-term safety and effectiveness are being evaluated in LOWER
- LOWER is a global long-term prospective observational treatment registry
- The rationale for LOWER and the study design are presented here

BackgroundLomitapide is an orally active selective inhibitor of microsomal triglyceride transfer protein approved as adjunctive therapy for homozygous familial hypercholesterolemia (HoFH). The Lomitapide Observational Worldwide Evaluation Registry (LOWER) is a global, long-term, prospective, observational treatment registry established as a regulatory requirement.ObjectivesLOWER will evaluate the long-term safety and effectiveness of lomitapide in clinical practice. The objectives include evaluation of the occurrence of events of special interest and assessment of the long-term effectiveness of lomitapide in maintaining reduced serum lipid levels.MethodsLOWER is a noninterventional study open to eligible lomitapide-treated patients. At least 300 patients will be enrolled and followed for at least 10 years. Data will be collected in conjunction with usual care visits and analyzed annually. LOWER includes a cardiovascular imaging substudy; an independent pregnancy exposure registry is also open.ResultsEvents of special interest include hepatic abnormalities, gastrointestinal events, certain gastrointestinal tumors, major adverse cardiovascular events, and events associated with coagulopathy. Data will be collected on demographics, diagnosis, patient history, lomitapide dosing, concomitant treatment, lipid profile, and other laboratory results.ConclusionLOWER will assess the long-term safety, efficacy, and patterns of use of lomitapide, increase understanding of the benefit-to-risk profile, and add to knowledge of HoFH.