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Pamrevlumab, a Fully Human Monoclonal Antibody Targeting Connective Tissue Growth Factor, for Non-Ambulatory Patients with Duchenne Muscular Dystrophy

BACKGROUND: Duchenne muscular dystrophy (DMD) is a neuromuscular disease stemming from dystrophin gene mutations. Lack of dystrophin leads to progressive muscle damage and replacement of muscle with fibrotic and adipose tissue. Pamrevlumab (FG-3019), a fully human monoclonal antibody that binds to c...

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Autores principales: Connolly, Anne M., Zaidman, Craig M., Brandsema, John F., Phan, Han C., Tian, Cuixia, Zhang, Xueping, Li, Jack, Eisner, Mark D., Carrier, Ewa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10357134/
https://www.ncbi.nlm.nih.gov/pubmed/37248912
http://dx.doi.org/10.3233/JND-230019
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author Connolly, Anne M.
Zaidman, Craig M.
Brandsema, John F.
Phan, Han C.
Tian, Cuixia
Zhang, Xueping
Li, Jack
Eisner, Mark D.
Carrier, Ewa
author_facet Connolly, Anne M.
Zaidman, Craig M.
Brandsema, John F.
Phan, Han C.
Tian, Cuixia
Zhang, Xueping
Li, Jack
Eisner, Mark D.
Carrier, Ewa
author_sort Connolly, Anne M.
collection PubMed
description BACKGROUND: Duchenne muscular dystrophy (DMD) is a neuromuscular disease stemming from dystrophin gene mutations. Lack of dystrophin leads to progressive muscle damage and replacement of muscle with fibrotic and adipose tissue. Pamrevlumab (FG-3019), a fully human monoclonal antibody that binds to connective tissue growth factor (CTGF), is in Phase III development for treatment of DMD and other diseases. METHODS: MISSION (Study 079; NCT02606136) was an open-label, Phase II, single-arm trial of pamrevlumab in 21 non-ambulatory patients with DMD (aged≥12 years, receiving corticosteroids) who received 35-mg/kg intravenous infusions every 2 weeks for 2 years. The primary endpoint was change from baseline in percent predicted forced vital capacity (ppFVC). Secondary endpoints included other pulmonary function tests, upper limb function and strength assessments, and changes in upper arm fat and fibrosis scores on magnetic resonance imaging. RESULTS: Fifteen patients completed the trial. Annual change from baseline (SE) in ppFVC was –4.2 (0.7) (95% CI –5.5, –2.8). Rate of decline in ppFVC in pamrevlumab-treated patients was slower than observed in historical published trials of non-ambulatory patients. MISSION participants experienced slower-than-anticipated muscle function declines compared with natural history and historical published trials of non-ambulatory patients with DMD. Pamrevlumab was well-tolerated. Treatment-emergent adverse events were mild to moderate, and none led to study discontinuation. CONCLUSIONS: nti-CTGF therapy with pamrevlumab represents a potential treatment for DMD. The lack of internal control group limits the results.
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spelling pubmed-103571342023-07-21 Pamrevlumab, a Fully Human Monoclonal Antibody Targeting Connective Tissue Growth Factor, for Non-Ambulatory Patients with Duchenne Muscular Dystrophy Connolly, Anne M. Zaidman, Craig M. Brandsema, John F. Phan, Han C. Tian, Cuixia Zhang, Xueping Li, Jack Eisner, Mark D. Carrier, Ewa J Neuromuscul Dis Research Report BACKGROUND: Duchenne muscular dystrophy (DMD) is a neuromuscular disease stemming from dystrophin gene mutations. Lack of dystrophin leads to progressive muscle damage and replacement of muscle with fibrotic and adipose tissue. Pamrevlumab (FG-3019), a fully human monoclonal antibody that binds to connective tissue growth factor (CTGF), is in Phase III development for treatment of DMD and other diseases. METHODS: MISSION (Study 079; NCT02606136) was an open-label, Phase II, single-arm trial of pamrevlumab in 21 non-ambulatory patients with DMD (aged≥12 years, receiving corticosteroids) who received 35-mg/kg intravenous infusions every 2 weeks for 2 years. The primary endpoint was change from baseline in percent predicted forced vital capacity (ppFVC). Secondary endpoints included other pulmonary function tests, upper limb function and strength assessments, and changes in upper arm fat and fibrosis scores on magnetic resonance imaging. RESULTS: Fifteen patients completed the trial. Annual change from baseline (SE) in ppFVC was –4.2 (0.7) (95% CI –5.5, –2.8). Rate of decline in ppFVC in pamrevlumab-treated patients was slower than observed in historical published trials of non-ambulatory patients. MISSION participants experienced slower-than-anticipated muscle function declines compared with natural history and historical published trials of non-ambulatory patients with DMD. Pamrevlumab was well-tolerated. Treatment-emergent adverse events were mild to moderate, and none led to study discontinuation. CONCLUSIONS: nti-CTGF therapy with pamrevlumab represents a potential treatment for DMD. The lack of internal control group limits the results. IOS Press 2023-07-04 /pmc/articles/PMC10357134/ /pubmed/37248912 http://dx.doi.org/10.3233/JND-230019 Text en © 2023 – The authors. Published by IOS Press https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY 4.0) License (https://creativecommons.org/licenses/by/4.0/)
spellingShingle Research Report
Connolly, Anne M.
Zaidman, Craig M.
Brandsema, John F.
Phan, Han C.
Tian, Cuixia
Zhang, Xueping
Li, Jack
Eisner, Mark D.
Carrier, Ewa
Pamrevlumab, a Fully Human Monoclonal Antibody Targeting Connective Tissue Growth Factor, for Non-Ambulatory Patients with Duchenne Muscular Dystrophy
title Pamrevlumab, a Fully Human Monoclonal Antibody Targeting Connective Tissue Growth Factor, for Non-Ambulatory Patients with Duchenne Muscular Dystrophy
title_full Pamrevlumab, a Fully Human Monoclonal Antibody Targeting Connective Tissue Growth Factor, for Non-Ambulatory Patients with Duchenne Muscular Dystrophy
title_fullStr Pamrevlumab, a Fully Human Monoclonal Antibody Targeting Connective Tissue Growth Factor, for Non-Ambulatory Patients with Duchenne Muscular Dystrophy
title_full_unstemmed Pamrevlumab, a Fully Human Monoclonal Antibody Targeting Connective Tissue Growth Factor, for Non-Ambulatory Patients with Duchenne Muscular Dystrophy
title_short Pamrevlumab, a Fully Human Monoclonal Antibody Targeting Connective Tissue Growth Factor, for Non-Ambulatory Patients with Duchenne Muscular Dystrophy
title_sort pamrevlumab, a fully human monoclonal antibody targeting connective tissue growth factor, for non-ambulatory patients with duchenne muscular dystrophy
topic Research Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10357134/
https://www.ncbi.nlm.nih.gov/pubmed/37248912
http://dx.doi.org/10.3233/JND-230019
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