Cargando…

Pharmacological Therapies of Spinal Muscular Atrophy: A Narrative Review of Preclinical, Clinical–Experimental, and Real-World Evidence

Spinal muscular atrophy (SMA) is a rare neuromuscular disease, with an estimated incidence of about 1 in 10,000 live births. To date, three orphan drugs have been approved for the treatment of SMA: nusinersen, onasemnogene abeparvovec, and risdiplam. The aim of this narrative review was to provide a...

Descripción completa

Detalles Bibliográficos
Autores principales: Crisafulli, Salvatore, Boccanegra, Brigida, Vitturi, Giacomo, Trifirò, Gianluca, De Luca, Annamaria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10605203/
https://www.ncbi.nlm.nih.gov/pubmed/37891814
http://dx.doi.org/10.3390/brainsci13101446
_version_ 1785127017030615040
author Crisafulli, Salvatore
Boccanegra, Brigida
Vitturi, Giacomo
Trifirò, Gianluca
De Luca, Annamaria
author_facet Crisafulli, Salvatore
Boccanegra, Brigida
Vitturi, Giacomo
Trifirò, Gianluca
De Luca, Annamaria
author_sort Crisafulli, Salvatore
collection PubMed
description Spinal muscular atrophy (SMA) is a rare neuromuscular disease, with an estimated incidence of about 1 in 10,000 live births. To date, three orphan drugs have been approved for the treatment of SMA: nusinersen, onasemnogene abeparvovec, and risdiplam. The aim of this narrative review was to provide an overview of the pre- and post-marketing evidence on the pharmacological treatments approved for the treatment of SMA by identifying preclinical and clinical studies registered in clinicaltrials.gov and in the EU PAS register from their inception until the 4 January 2023. The preclinical evidence on the drugs approved for SMA allowed a significant acceleration in the experimental phase of these drugs. However, since these drugs had been authorized through accelerated programs, the conduction of post-marketing studies was requested as a condition of their marketing approval to better understand their risk–benefit profiles in real-world settings. As of the 4 January 2023, a total of 69 post-marketing studies concerning the three orphan drugs approved for SMA were identified in clinicaltrials.gov (N = 65; 94.2%) and in the EU PAS register (N = 4; 5.8%). Currently, ongoing studies are primarily aimed at providing evidence concerning the risk–benefit profile of the three drugs in specific populations that were not included in the pivotal trials and to investigate the long-term safety and clinical benefits of these drugs. Real-world data sources collecting information regarding the natural history of the disease and post-marketing surveillance of the available therapies are increasingly becoming essential for generating real-world evidence on this rare disease and its orphan drugs.
format Online
Article
Text
id pubmed-10605203
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-106052032023-10-28 Pharmacological Therapies of Spinal Muscular Atrophy: A Narrative Review of Preclinical, Clinical–Experimental, and Real-World Evidence Crisafulli, Salvatore Boccanegra, Brigida Vitturi, Giacomo Trifirò, Gianluca De Luca, Annamaria Brain Sci Review Spinal muscular atrophy (SMA) is a rare neuromuscular disease, with an estimated incidence of about 1 in 10,000 live births. To date, three orphan drugs have been approved for the treatment of SMA: nusinersen, onasemnogene abeparvovec, and risdiplam. The aim of this narrative review was to provide an overview of the pre- and post-marketing evidence on the pharmacological treatments approved for the treatment of SMA by identifying preclinical and clinical studies registered in clinicaltrials.gov and in the EU PAS register from their inception until the 4 January 2023. The preclinical evidence on the drugs approved for SMA allowed a significant acceleration in the experimental phase of these drugs. However, since these drugs had been authorized through accelerated programs, the conduction of post-marketing studies was requested as a condition of their marketing approval to better understand their risk–benefit profiles in real-world settings. As of the 4 January 2023, a total of 69 post-marketing studies concerning the three orphan drugs approved for SMA were identified in clinicaltrials.gov (N = 65; 94.2%) and in the EU PAS register (N = 4; 5.8%). Currently, ongoing studies are primarily aimed at providing evidence concerning the risk–benefit profile of the three drugs in specific populations that were not included in the pivotal trials and to investigate the long-term safety and clinical benefits of these drugs. Real-world data sources collecting information regarding the natural history of the disease and post-marketing surveillance of the available therapies are increasingly becoming essential for generating real-world evidence on this rare disease and its orphan drugs. MDPI 2023-10-10 /pmc/articles/PMC10605203/ /pubmed/37891814 http://dx.doi.org/10.3390/brainsci13101446 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Crisafulli, Salvatore
Boccanegra, Brigida
Vitturi, Giacomo
Trifirò, Gianluca
De Luca, Annamaria
Pharmacological Therapies of Spinal Muscular Atrophy: A Narrative Review of Preclinical, Clinical–Experimental, and Real-World Evidence
title Pharmacological Therapies of Spinal Muscular Atrophy: A Narrative Review of Preclinical, Clinical–Experimental, and Real-World Evidence
title_full Pharmacological Therapies of Spinal Muscular Atrophy: A Narrative Review of Preclinical, Clinical–Experimental, and Real-World Evidence
title_fullStr Pharmacological Therapies of Spinal Muscular Atrophy: A Narrative Review of Preclinical, Clinical–Experimental, and Real-World Evidence
title_full_unstemmed Pharmacological Therapies of Spinal Muscular Atrophy: A Narrative Review of Preclinical, Clinical–Experimental, and Real-World Evidence
title_short Pharmacological Therapies of Spinal Muscular Atrophy: A Narrative Review of Preclinical, Clinical–Experimental, and Real-World Evidence
title_sort pharmacological therapies of spinal muscular atrophy: a narrative review of preclinical, clinical–experimental, and real-world evidence
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10605203/
https://www.ncbi.nlm.nih.gov/pubmed/37891814
http://dx.doi.org/10.3390/brainsci13101446
work_keys_str_mv AT crisafullisalvatore pharmacologicaltherapiesofspinalmuscularatrophyanarrativereviewofpreclinicalclinicalexperimentalandrealworldevidence
AT boccanegrabrigida pharmacologicaltherapiesofspinalmuscularatrophyanarrativereviewofpreclinicalclinicalexperimentalandrealworldevidence
AT vitturigiacomo pharmacologicaltherapiesofspinalmuscularatrophyanarrativereviewofpreclinicalclinicalexperimentalandrealworldevidence
AT trifirogianluca pharmacologicaltherapiesofspinalmuscularatrophyanarrativereviewofpreclinicalclinicalexperimentalandrealworldevidence
AT delucaannamaria pharmacologicaltherapiesofspinalmuscularatrophyanarrativereviewofpreclinicalclinicalexperimentalandrealworldevidence