Lorraine L. Janeczko, MPH
The international LOWER (Lomitapide Observational Worldwide Evaluation Registry) is now under way and accepting physicians and their eligible patients being treated with lomitapide, according to a poster presented at the National Lipid Association Scientific Sessions, June 10-14, 2015, in Chicago, Illinois.
Lead study author James A. Underberg, MD, of New York University Langone Medical Center in New York City, and colleagues have designed the voluntary LOWER to assess the long-term safety, efficacy, and patterns of use of lomitapide, and to help researchers better understand homozygous familial hypercholesterolemia (HoFH) by gathering long-term clinical information about patients who use the drug in the real world.
LOWER, sponsored by Aegerion Pharmaceuticals, is a regulatory requirement of the Food and Drug Administrations of the United States and Taiwan, the European Medicines Agency, and Health Canada. The registry opened to enrollment in March 2014, enrolled 84 patients worldwide by March 2015, and expects to include 300 patients by March 2018.
The registry will enroll patients in the United States, Canada, Latin America, Europe, and Asia, and follow them for at least 10 years. The registry will remain open indefinitely in the European Union (EU), but in non-EU countries it will close when at least 300 enrolled patients have been followed for 10 years, to provide roughly 3000 patient-years of exposure. Data will be collected during all usual care visits and analyzed yearly.
Patients age 18 years and older who have begun treatment with lomitapide within 15 months prior to enrolling in LOWER will be enrolled, but those receiving lomitapide in clinical trials or involved in certain other studies will be excluded.
Information that LOWER collects includes lomitapide dosing; demographic and diagnostic information; family and medical history; medications and dietary supplements; apheresis schedule; weight and body mass index; hepatic, gastrointestinal, and cardiovascular procedures; diagnostic tests; lipid profile; hepatic safety; creatine kinase; and pregnancy testing.
Two offshoots of LOWER include the Pregnancy Exposure Registry (PER) and the Effects of Lomitapide on Carotid and Aortic Atherosclerosis in Patients Treated with Lomitapide in Usual Care (CAPTURE) substudy.
PER is independent of LOWER and will study the effects of lomitapide on pregnancy outcomes, including congenital anomalies, in women exposed to the drug while pregnant. PER will remain open for the lifetime of LOWER and will collect data during pregnancy, within 4 weeks after the estimated delivery date, and for live births, during pediatric visits at 12 weeks and 12 months of age.
CAPTURE, a cardiovascular imaging substudy of patients in the United States, Canada, and Europe who are enrolled in LOWER, will examine the effects of lomitapide on cardiovascular morbidity and mortality.
LOWER will evaluate events of special interest, including hepatic, gastrointestinal, and coagulopathy-related events, cardiovascular outcomes, tumors, and pregnancy outcomes (through PER). LOWER will also provide data on long-term lipid control and adherence to product label screening and monitoring recommendations.
About Homozygous Familial Hypercholesterolemia (HoFH)
Homozygous familial hypercholesterolemia is a rare genetic disease. Patients with HoFH have elevated low-density lipoprotein cholesterol (LDL-C) levels and are at increased risk of early-onset cardiovascular disease.
Underlying mutations in the LDL receptor cause receptor dysfunction, and leave patients with only minimal-to-modest LDL-C-level reduction with conventional lipid-lowering therapies.
Lomitapide is an oral selective inhibitor of microsomal triglyceride transfer protein (MTP) that reduces circulating LDL-C. The drug has been approved in the United States, the European Union, and other countries to reduce LDL-C levels in adult patients with HoFH as an adjunct to other lipid-lowering treatments. In clinical trials, lomitapide has significantly reduced LDL-C, but no real-world studies have evaluated its long-term safety, effectiveness, and patterns of use.
Taking lomitapide during pregnancy may cause fetal damage. Women who might become pregnant should use contraception, and before they begin taking the drug, make certain that they are not pregnant.
How To Enroll In LOWER
LOWER is now actively enrolling doctors and their eligible patients.
For more information, patients can email firstname.lastname@example.org or call the telephone number appropriate for their country:
--USA and Canada: 1-877-902-4099
--EU and Taiwan: 00-800-000-10-20
1. Underberg JA, Kastelein J, Kastelein J, et al. LOWER: a registry evaluating long-term lomitapide use in patients with homozygous familial hypercholesterolemia. Presented at: the National Lipid Association Scientific Sessions 2015; June 11-14, 2015; Chicago, IL. Abstract 145.