Long-term safety and efficacy of lomitapide in patients with homozygous familial hypercholesterolemia: Five-year data from the Lomitapide Observational Worldwide Evaluation Registry (LOWER).
Homozygous familial hypercholesterolemia
Lipid-lowering therapy
Lomitapide
Long-term efficacy and safety
Registries
Journal
Journal of clinical lipidology
ISSN: 1933-2874
Titre abrégé: J Clin Lipidol
Pays: United States
ID NLM: 101300157
Informations de publication
Date de publication:
Historique:
received:
03
02
2020
revised:
06
08
2020
accepted:
12
08
2020
pubmed:
8
10
2020
medline:
27
8
2021
entrez:
7
10
2020
Statut:
ppublish
Résumé
Lomitapide is a lipid-lowering agent indicated as adjunct therapy for homozygous familial hypercholesterolemia (HoFH) in adults. The Lomitapide Observational Worldwide Evaluation Registry is an international, observational registry assessing long-term safety, tolerability, and effectiveness of lomitapide. This analysis examines 5-year data from the registry up to February 28, 2019. At lomitapide initiation, enrolled patients (N = 187) were a mean ± SD age of 52.2 ± 15.3 years with a mean ± SD low-density lipoprotein cholesterol (LDL-C) measurement of 232.0 ± 94.9 mg/dL. Exposure duration was up to 5.9 years (median, 1.98 years), and median dose was 10 mg (range, 5 mg QOD to 40 mg QD). After treatment, there was a mean 33% reduction in LDL-C (45% in patients remaining on lomitapide), 65.4% achieved LDL-C <100 mg/dL, and 41.1% achieved LDL-C <70 mg/dL. At year 4, the absolute mean change from baseline in LDL-C was -70.6 ± 76.21 mg/dL. Adverse events (AEs) occurred in 75.7% of patients, treatment-related AEs in 54.6%, and serious AEs in 22.2%; 23.2% of patients discontinued because of an AE. Events of special interest included gastrointestinal (13.5%), hepatic (15.1%), major adverse cardiovascular events (10.8%, resulting in 5 deaths), tumors (2.2%), and 4 pregnancies in 3 of 32 women of childbearing potential. The efficacy and safety of lomitapide are consistent with phase III trial data despite using a much lower median dose of 10 mg vs 40 mg in phase III. No new safety signals were identified. The incidence of AEs, serious AEs, and aminotransferase alanine transaminase elevations was lower than that seen in the phase III trial, potentially related to the lower median dose.
Sections du résumé
BACKGROUND
Lomitapide is a lipid-lowering agent indicated as adjunct therapy for homozygous familial hypercholesterolemia (HoFH) in adults.
OBJECTIVE
The Lomitapide Observational Worldwide Evaluation Registry is an international, observational registry assessing long-term safety, tolerability, and effectiveness of lomitapide.
METHODS
This analysis examines 5-year data from the registry up to February 28, 2019.
RESULTS
At lomitapide initiation, enrolled patients (N = 187) were a mean ± SD age of 52.2 ± 15.3 years with a mean ± SD low-density lipoprotein cholesterol (LDL-C) measurement of 232.0 ± 94.9 mg/dL. Exposure duration was up to 5.9 years (median, 1.98 years), and median dose was 10 mg (range, 5 mg QOD to 40 mg QD). After treatment, there was a mean 33% reduction in LDL-C (45% in patients remaining on lomitapide), 65.4% achieved LDL-C <100 mg/dL, and 41.1% achieved LDL-C <70 mg/dL. At year 4, the absolute mean change from baseline in LDL-C was -70.6 ± 76.21 mg/dL. Adverse events (AEs) occurred in 75.7% of patients, treatment-related AEs in 54.6%, and serious AEs in 22.2%; 23.2% of patients discontinued because of an AE. Events of special interest included gastrointestinal (13.5%), hepatic (15.1%), major adverse cardiovascular events (10.8%, resulting in 5 deaths), tumors (2.2%), and 4 pregnancies in 3 of 32 women of childbearing potential.
CONCLUSION
The efficacy and safety of lomitapide are consistent with phase III trial data despite using a much lower median dose of 10 mg vs 40 mg in phase III. No new safety signals were identified. The incidence of AEs, serious AEs, and aminotransferase alanine transaminase elevations was lower than that seen in the phase III trial, potentially related to the lower median dose.
Identifiants
pubmed: 33023859
pii: S1933-2874(20)30251-8
doi: 10.1016/j.jacl.2020.08.006
pii:
doi:
Substances chimiques
BMS201038
0
Benzimidazoles
0
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
807-817Informations de copyright
Copyright © 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.