Real-World Outcomes with Lomitapide Use in Paediatric Patients with Homozygous Familial Hypercholesterolaemia

Tawfeg Ben-Omran; Luis Masana; Genovefa Kolovou; Gema Ariceta; F. Javier Nóvoa; Allan M. Lund; Martin P. Bogsrud; María Araujo; Osamah Hussein; Daiana Ibarretxe; Rosa M. Sanchez-Hernández; Raul D. Santos

doi:10.1007/s12325-019-00985-8

Real-World Outcomes with Lomitapide Use in Paediatric Patients with Homozygous Familial Hypercholesterolaemia

Tawfeg Ben-Omran, Luis Masana, Genovefa Kolovou, Gema Ariceta, F. Javier Nóvoa, Allan M. Lund, Martin P. Bogsrud, María Araujo, Osamah Hussein, Daiana Ibarretxe, Rosa M. Sanchez-Hernández, Raul D. Santos

Bar-Ilan University - Azrieli Faculty of Medicine

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

Abstract

Introduction: Homozygous familial hypercholesterolaemia (HoFH) is a rare, autosomal disease affecting the clearance of low-density lipoprotein cholesterol (LDL-C) from circulation, and leading to early-onset atherosclerotic cardiovascular disease (ASCVD). Treatment consists mainly of statins, lipoprotein apheresis (LA) and, more recently, the microsomal triglyceride transfer protein inhibitor lomitapide. Lomitapide is not licensed for use in children, but has been made available through an expanded access programme or on a named patient basis. Methods: This case series includes 11 HoFH patients in 10 different centres in eight countries, less than 18 years of age (mean 11.6 ± 1.1 years, 64% male), with signs of ASCVD, and who have received treatment with lomitapide (mean dose 24.5 ± 4.3 mg/day; mean exposure 20.0 ± 2.9 months). Background lipid-lowering therapy was given according to local protocols. Lomitapide was commenced with a stepwise dose escalation from 2.5 mg or 5 mg/day; dietary advice and vitamin supplements were provided as per the product label for adults. Laboratory analysis was conducted as part of regular clinical care. Results: In the 11 cases, mean baseline LDL-C was 419 ± 74.6 mg/dL and was markedly reduced by lomitapide to a nadir of 176.7 ± 46.3 mg/dL (58.4 ± 6.8% decrease). Six patients achieved recommended target levels for children below 135 mg/dL, five of whom had LA frequency reduced. In one case, LDL-C levels were close to target when lomitapide was started but remained stable despite 75% reduction in LA frequency (from twice weekly to biweekly). Adverse events were mainly gastrointestinal in nature, occurred early in the treatment course and were well managed. Three patients with excursions in liver function tests were managed chiefly without intervention; two patients had decreases in lomitapide dose. Conclusions: Lomitapide demonstrated promising effectiveness in paediatric HoFH patients. Adverse events were manageable, and the clinical profile of the drug is apparently similar to that in adult patients. Funding: Amryt Pharma.

Original language	English
Pages (from-to)	1786-1811
Number of pages	26
Journal	Advances in Therapy
Volume	36
Issue number	7
DOIs	https://doi.org/10.1007/s12325-019-00985-8
State	Published - 1 Jul 2019

Bibliographical note

Publisher Copyright:
© 2019, The Author(s).

Funding

Amryt Pharma was not involved in design, data collection or decision to publish. Access to lomitapide was supported by Amryt Pharmaceuticals DAC. Article processing charges and open access fee were funded by Amryt Pharma. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. Luis Masana received lectures and advisory fees from Amgen, Sanofi, MSD, Myland and Daichii Sankyo. Genovefa Kolovou has given talks, attended conferences sponsored by Amgen, Angelini, MSD, Lilly, Vianex and Sanofi. Martin P. Bogsrud received honoraria relating consulting from Amgen, Sanofi, MSD, Boehringer Ingelheim and Kaneka. Osamah Hussein received honoraria relating to consulting for Megapharma. Daiana Ibarretxe received honoraria related speaker activities for Sanofi, MSD and Rubio. Raul D. Santos received honoraria related to consulting and speaker activities from AstraZeneca, Amgen, Akcea, Kowa, Esperion, MSD, Novo Nordisk and Sanofi. Raul D. Santos is a recipient of a scholarship from the Conselho Nacional de Pesquisa e Desenvolvimento Tecnologico (CNPq) process # 303734/2018-3. Tawfeg Ben-Omran, Gema Ariceta, F. Javier Nóvoa, Allan M. Lund, María Araujo and Rosa M. Sanchez-Hernández have nothing to disclose. The authors would like to thank Nigel Eastmond of Eastmond Medicomm Ltd for editorial support and data analysis that was funded by Amryt Pharma. The authors would also like to thank the patients who contributed data for the paper and provided kind permission for publication. Amryt Pharma was not involved in design, data collection or decision to publish. Access to lomitapide was supported by Amryt Pharmaceuticals DAC. Article processing charges and open access fee were funded by Amryt Pharma. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. The authors would like to thank Nigel Eastmond of Eastmond Medicomm Ltd for editorial support and data analysis that was funded by Amryt Pharma. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Luis Masana received lectures and advisory fees from Amgen, Sanofi, MSD, Myland and Daichii Sankyo. Genovefa Kolovou has given talks, attended conferences sponsored by Amgen, Angelini, MSD, Lilly, Vianex and Sanofi. Martin P. Bogsrud received honoraria relating consulting from Amgen, Sanofi, MSD, Boehringer Ingelheim and Kaneka. Osamah Hussein received honoraria relating to consulting for Megapharma. Daiana Ibarretxe received honoraria related speaker activities for Sanofi, MSD and Rubio. Raul D. Santos received honoraria related to consulting and speaker activities from AstraZeneca, Amgen, Akcea, Kowa, Esperion, MSD, Novo Nordisk and Sanofi. Raul D. Santos is a recipient of a scholarship from the Conselho Nacional de Pesquisa e Desenvolvimento Tecnologico (CNPq) process # 303734/2018-3. Tawfeg Ben-Omran, Gema Ariceta, F. Javier N?voa, Allan M. Lund, Mar?a Araujo and Rosa M. Sanchez-Hern?ndez have nothing to disclose. This case series was not subject to ethic board approval as it includes cases treated in the normal course of care, but all patients provided permission for their data to be published. All data generated or analyzed during this study are included in this published article/as supplementary information files.

Funders	Funder number
Amryt Pharma
Amryt Pharmaceuticals DAC
Conselho Nacional de Pesquisa e Desenvolvimento Tecnologico	303734/2018-3
Myland and Daichii Sankyo
Amgen
AstraZeneca
Sanofi
Meso Scale Diagnostics
Boehringer Ingelheim
Amryt Pharma
Novo Nordisk

Keywords

Adverse events
Atherosclerosis
Cardiology
Homozygous familial hypercholesterolaemia
Lipidology
Lomitapide
Low-density lipoprotein cholesterol
Paediatric
Patient cases
Real-world data

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s12325-019-00985-8

Cite this

Ben-Omran, T., Masana, L., Kolovou, G., Ariceta, G., Nóvoa, F. J., Lund, A. M., Bogsrud, M. P., Araujo, M., Hussein, O., Ibarretxe, D., Sanchez-Hernández, R. M., & Santos, R. D. (2019). Real-World Outcomes with Lomitapide Use in Paediatric Patients with Homozygous Familial Hypercholesterolaemia. Advances in Therapy, 36(7), 1786-1811. https://doi.org/10.1007/s12325-019-00985-8

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title = "Real-World Outcomes with Lomitapide Use in Paediatric Patients with Homozygous Familial Hypercholesterolaemia",

abstract = "Introduction: Homozygous familial hypercholesterolaemia (HoFH) is a rare, autosomal disease affecting the clearance of low-density lipoprotein cholesterol (LDL-C) from circulation, and leading to early-onset atherosclerotic cardiovascular disease (ASCVD). Treatment consists mainly of statins, lipoprotein apheresis (LA) and, more recently, the microsomal triglyceride transfer protein inhibitor lomitapide. Lomitapide is not licensed for use in children, but has been made available through an expanded access programme or on a named patient basis. Methods: This case series includes 11 HoFH patients in 10 different centres in eight countries, less than 18 years of age (mean 11.6 ± 1.1 years, 64% male), with signs of ASCVD, and who have received treatment with lomitapide (mean dose 24.5 ± 4.3 mg/day; mean exposure 20.0 ± 2.9 months). Background lipid-lowering therapy was given according to local protocols. Lomitapide was commenced with a stepwise dose escalation from 2.5 mg or 5 mg/day; dietary advice and vitamin supplements were provided as per the product label for adults. Laboratory analysis was conducted as part of regular clinical care. Results: In the 11 cases, mean baseline LDL-C was 419 ± 74.6 mg/dL and was markedly reduced by lomitapide to a nadir of 176.7 ± 46.3 mg/dL (58.4 ± 6.8% decrease). Six patients achieved recommended target levels for children below 135 mg/dL, five of whom had LA frequency reduced. In one case, LDL-C levels were close to target when lomitapide was started but remained stable despite 75% reduction in LA frequency (from twice weekly to biweekly). Adverse events were mainly gastrointestinal in nature, occurred early in the treatment course and were well managed. Three patients with excursions in liver function tests were managed chiefly without intervention; two patients had decreases in lomitapide dose. Conclusions: Lomitapide demonstrated promising effectiveness in paediatric HoFH patients. Adverse events were manageable, and the clinical profile of the drug is apparently similar to that in adult patients. Funding: Amryt Pharma.",

keywords = "Adverse events, Atherosclerosis, Cardiology, Homozygous familial hypercholesterolaemia, Lipidology, Lomitapide, Low-density lipoprotein cholesterol, Paediatric, Patient cases, Real-world data",

author = "Tawfeg Ben-Omran and Luis Masana and Genovefa Kolovou and Gema Ariceta and N{\'o}voa, {F. Javier} and Lund, {Allan M.} and Bogsrud, {Martin P.} and Mar{\'i}a Araujo and Osamah Hussein and Daiana Ibarretxe and Sanchez-Hern{\'a}ndez, {Rosa M.} and Santos, {Raul D.}",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = jul,

day = "1",

doi = "10.1007/s12325-019-00985-8",

language = "אנגלית",

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pages = "1786--1811",

journal = "Advances in Therapy",

issn = "0741-238X",

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Ben-Omran, T, Masana, L, Kolovou, G, Ariceta, G, Nóvoa, FJ, Lund, AM, Bogsrud, MP, Araujo, M, Hussein, O, Ibarretxe, D, Sanchez-Hernández, RM & Santos, RD 2019, 'Real-World Outcomes with Lomitapide Use in Paediatric Patients with Homozygous Familial Hypercholesterolaemia', Advances in Therapy, vol. 36, no. 7, pp. 1786-1811. https://doi.org/10.1007/s12325-019-00985-8

TY - JOUR

T1 - Real-World Outcomes with Lomitapide Use in Paediatric Patients with Homozygous Familial Hypercholesterolaemia

AU - Ben-Omran, Tawfeg

AU - Masana, Luis

AU - Kolovou, Genovefa

AU - Ariceta, Gema

AU - Nóvoa, F. Javier

AU - Lund, Allan M.

AU - Bogsrud, Martin P.

AU - Araujo, María

AU - Hussein, Osamah

AU - Ibarretxe, Daiana

AU - Sanchez-Hernández, Rosa M.

AU - Santos, Raul D.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Introduction: Homozygous familial hypercholesterolaemia (HoFH) is a rare, autosomal disease affecting the clearance of low-density lipoprotein cholesterol (LDL-C) from circulation, and leading to early-onset atherosclerotic cardiovascular disease (ASCVD). Treatment consists mainly of statins, lipoprotein apheresis (LA) and, more recently, the microsomal triglyceride transfer protein inhibitor lomitapide. Lomitapide is not licensed for use in children, but has been made available through an expanded access programme or on a named patient basis. Methods: This case series includes 11 HoFH patients in 10 different centres in eight countries, less than 18 years of age (mean 11.6 ± 1.1 years, 64% male), with signs of ASCVD, and who have received treatment with lomitapide (mean dose 24.5 ± 4.3 mg/day; mean exposure 20.0 ± 2.9 months). Background lipid-lowering therapy was given according to local protocols. Lomitapide was commenced with a stepwise dose escalation from 2.5 mg or 5 mg/day; dietary advice and vitamin supplements were provided as per the product label for adults. Laboratory analysis was conducted as part of regular clinical care. Results: In the 11 cases, mean baseline LDL-C was 419 ± 74.6 mg/dL and was markedly reduced by lomitapide to a nadir of 176.7 ± 46.3 mg/dL (58.4 ± 6.8% decrease). Six patients achieved recommended target levels for children below 135 mg/dL, five of whom had LA frequency reduced. In one case, LDL-C levels were close to target when lomitapide was started but remained stable despite 75% reduction in LA frequency (from twice weekly to biweekly). Adverse events were mainly gastrointestinal in nature, occurred early in the treatment course and were well managed. Three patients with excursions in liver function tests were managed chiefly without intervention; two patients had decreases in lomitapide dose. Conclusions: Lomitapide demonstrated promising effectiveness in paediatric HoFH patients. Adverse events were manageable, and the clinical profile of the drug is apparently similar to that in adult patients. Funding: Amryt Pharma.

AB - Introduction: Homozygous familial hypercholesterolaemia (HoFH) is a rare, autosomal disease affecting the clearance of low-density lipoprotein cholesterol (LDL-C) from circulation, and leading to early-onset atherosclerotic cardiovascular disease (ASCVD). Treatment consists mainly of statins, lipoprotein apheresis (LA) and, more recently, the microsomal triglyceride transfer protein inhibitor lomitapide. Lomitapide is not licensed for use in children, but has been made available through an expanded access programme or on a named patient basis. Methods: This case series includes 11 HoFH patients in 10 different centres in eight countries, less than 18 years of age (mean 11.6 ± 1.1 years, 64% male), with signs of ASCVD, and who have received treatment with lomitapide (mean dose 24.5 ± 4.3 mg/day; mean exposure 20.0 ± 2.9 months). Background lipid-lowering therapy was given according to local protocols. Lomitapide was commenced with a stepwise dose escalation from 2.5 mg or 5 mg/day; dietary advice and vitamin supplements were provided as per the product label for adults. Laboratory analysis was conducted as part of regular clinical care. Results: In the 11 cases, mean baseline LDL-C was 419 ± 74.6 mg/dL and was markedly reduced by lomitapide to a nadir of 176.7 ± 46.3 mg/dL (58.4 ± 6.8% decrease). Six patients achieved recommended target levels for children below 135 mg/dL, five of whom had LA frequency reduced. In one case, LDL-C levels were close to target when lomitapide was started but remained stable despite 75% reduction in LA frequency (from twice weekly to biweekly). Adverse events were mainly gastrointestinal in nature, occurred early in the treatment course and were well managed. Three patients with excursions in liver function tests were managed chiefly without intervention; two patients had decreases in lomitapide dose. Conclusions: Lomitapide demonstrated promising effectiveness in paediatric HoFH patients. Adverse events were manageable, and the clinical profile of the drug is apparently similar to that in adult patients. Funding: Amryt Pharma.

KW - Adverse events

KW - Atherosclerosis

KW - Cardiology

KW - Homozygous familial hypercholesterolaemia

KW - Lipidology

KW - Lomitapide

KW - Low-density lipoprotein cholesterol

KW - Paediatric

KW - Patient cases

KW - Real-world data

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AN - SCOPUS:85066083633

SN - 0741-238X

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JO - Advances in Therapy

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IS - 7

ER -

Real-World Outcomes with Lomitapide Use in Paediatric Patients with Homozygous Familial Hypercholesterolaemia

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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