Efficacy of Long-Term Treatment of Autosomal Recessive Hypercholesterolemia With Lomitapide: A Subanalysis of the Pan-European Lomitapide Study

Laura D’Erasmo*, Antonina Giammanco, the Italian and European Working Group on Lomitapide in HoFH, Patrizia Suppressa, Chiara Pavanello, Gabriella Iannuzzo, Alessia Di Costanzo, Daniele Tramontano, Ilenia Minicocci, Simone Bini, Anja Vogt, Kim Stewards, Jeanine Roeters Van Lennep, Stefano Bertolini, Marcello Arca

*Corresponding author for this work

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Abstract

Background and aim: Autosomal recessive hypercholesterolemia (ARH) is a rare autosomal recessive disorder of low-density lipoprotein (LDL) metabolism caused by pathogenic variants in the LDLRAP1 gene. Like homozygous familial hypercholesterolemia, ARH is resistant to conventional LDL-lowering medications and causes a high risk of atherosclerotic cardiovascular diseases (ASCVDs) and aortic valve stenosis. Lomitapide is emerging as an efficacious therapy in classical HoFH, but few data are available for ARH. Results: This is a subanalysis carried out on nine ARH patients included in the Pan-European Lomitapide Study. The age at starting lomitapide was 46 (interquartile range (IQR), 39.0–65.5) years, with a median treatment duration of 31.0 (IQR 14.0–40.5) months. At baseline, four (44.4%) patients had hypertension, one (11.1%) had diabetes mellitus, two (22.2%) were active smokers, and five (55.5%) reported ASCVD. The baseline LDL-C was 257.0 (IQR, 165.3–309.2) mg/dL. All patients were on statins plus ezetimibe, three were receiving Lipoprotein apheresis (LA), and one was also receiving proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i). The addition of lomitapide (mean dose, 10 mg) resulted in the achievement of a median on-treatment LDL-C of 101.7 mg/dL (IQR, 71.3–138.3; 60.4% reduction from baseline), with a best LDL-C value of 68.0 mg/dL (IQR, 43.7–86.7; 73.5% reduction from baseline). During follow-up, one patient stopped both PCSK9i and LA. Recurrence of ASCVD events was reported in one patient. The median on-treatment aspartate transaminase and alanine transaminase values were 31.1 (IQR, 22.6–48.3) U/L and 31.1 (IQR, 27.2–53.8) U/L, respectively. Among six ARH patients with available fibroscan examination, liver stiffness values recorded at the last visit were within the normal range (median, 4.7 KPa; IQR, 3.6–5.3 KPa). Conclusion: Lomitapide is effective and safe in ARH therapy as well as in classical HoFH.

Original languageEnglish
Article number937750
JournalFrontiers in Genetics
Volume13
DOIs
Publication statusPublished - 22 Aug 2022

Bibliographical note

Funding Information:
LD'E has received personal fees for public speaking, consultancy or grant support from Amryt Pharmaceuticals, Akcea Therapeutics, Pfizer, Amgen, SOBI and Sanofi; ABC has served as a consultant for Amryt Pharmaceutical; and received lecturing fees from Amryt Pharmaceutical, MSD, Sanofi and AlfaSigma; MAV has served as a consultant for Amgen, Sanofi, Akcea, Novartin, Amgen; MA has received research grant support from Amryt Pharmaceutical, Amgen, IONIS, Akcea Therapeutics, Pfizer and Sanofi; has served as a consultant for Amgen, Aegerion, Akcea Therapeutics, Regeneron, Sanofi and Alfasigma and received lecturing fees from Amgen, Amryt Pharmaceuticals, Pfizer, Sanofi and AlfaSigma; GI has received personal fees for public speaking, consultancy or grant support from Amryt Pharmaceuticals, Akcea Therapeutics, Pfizer, Regeneron, Amgen and Sanofi; SD'A has received personal fees as advisor board from Akcea and IONIS; CP has received fees for public speaking and consultancy from SOBI, Akcea Therapeutics and Amryt Pharmaceuticals; LC has received personal fees for public speaking, consultancy or grant support from Abionyx Pharma, MedImmune, Alexion, Daichii-Sankyo, Pfizer, Akcea Therapeutics;JRVL has received grant support from Amryt Pharmaceuticals; CJ has received speaker, consultancy fees or research grants from Amgen, Sanofi, Amryt, Pfizer, Novartis, Akcea; EL reported non-financial support from HELLENIC ATHEROSCLEROSIS SOCIETY and personal fees from AMGEN, personal fees from NOVARTIS, MYLAN, SERVIER.

Funding Information:
This is a subanalysis of the Pan-European observational study that was supported by a grant in-aid from Amryt Pharmaceutical to LD'E and JRvL. In addition, LD'E received a grant in support of this project from Sapienza, University of Rome.

Publisher Copyright:
Copyright © 2022 D’Erasmo, Giammanco, Suppressa, Pavanello, Iannuzzo, Di Costanzo, Tramontano, Minicocci, Bini, Vogt, Stewards, Roeters Van Lennep, Bertolini, Arca and the Italian and European Working Group on Lomitapide in HoFH.

Funding Information:
This is a subanalysis of the Pan-European observational study that was supported by a grant in-aid from Amryt Pharmaceutical to LD'E and JRvL. In addition, LD'E received a grant in support of this project from Sapienza, University of Rome.

Funding Information:
This is a subanalysis of the Pan-European observational study that was supported by a grant in-aid from Amryt Pharmaceutical to LD'E and JRvL. In addition, LD'E received a grant in support of this project from Sapienza, University of Rome.

Publisher Copyright:
Copyright © 2022 D’Erasmo, Giammanco, Suppressa, Pavanello, Iannuzzo, Di Costanzo, Tramontano, Minicocci, Bini, Vogt, Stewards, Roeters Van Lennep, Bertolini, Arca and the Italian and European Working Group on Lomitapide in HoFH.

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