Risdiplam treatment has not led to retinal toxicity in patients with spinal muscular atrophy.
Journal
Annals of clinical and translational neurology
ISSN: 2328-9503
Titre abrégé: Ann Clin Transl Neurol
Pays: United States
ID NLM: 101623278
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
23
07
2020
revised:
07
10
2020
accepted:
07
10
2020
pubmed:
25
11
2020
medline:
9
10
2021
entrez:
24
11
2020
Statut:
ppublish
Résumé
Evaluation of ophthalmologic safety with focus on retinal safety in patients with spinal muscular atrophy (SMA) treated with risdiplam (EVRYSDI®), a survival of motor neuron 2 splicing modifier associated with retinal toxicity in monkeys. Risdiplam was approved recently for the treatment of patients with SMA, aged ≥ 2 months in the United States, and is currently under Health Authority review in the EU. Subjects included patients with SMA aged 2 months-60 years enrolled in the FIREFISH, SUNFISH, and JEWELFISH clinical trials for risdiplam. Ophthalmologic assessments, including functional assessments (age-appropriate visual acuity and visual field) and imaging (spectral domain optical coherence tomography [SD-OCT], fundus photography, and fundus autofluorescence [FAF]), were conducted at baseline and every 2-6 months depending on study and assessment. SD-OCT, FAF, fundus photography, and threshold perimetry were evaluated by an independent, masked reading center. Adverse events (AEs) were reported throughout the study. A total of 245 patients receiving risdiplam were assessed. Comprehensive, high-quality, ophthalmologic monitoring assessing retinal structure and visual function showed no retinal structural or functional changes. In the youngest patients, SD-OCT findings of normal retinal maturation were observed. AEs involving eye disorders were not suggestive of risdiplam-induced toxicity and resolved with ongoing treatment. Extensive ophthalmologic monitoring conducted in studies in patients with SMA confirmed that risdiplam does not induce ophthalmologic toxicity in pediatric or adult patients with SMA at the therapeutic dose. These results suggest that safety ophthalmologic monitoring is not needed in patients receiving risdiplam, as also reflected in the United States Prescribing Information for risdiplam.
Identifiants
pubmed: 33231373
doi: 10.1002/acn3.51239
pmc: PMC7818230
doi:
Substances chimiques
Azo Compounds
0
Neuromuscular Agents
0
Pyrimidines
0
Risdiplam
76RS4S2ET1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
54-65Informations de copyright
© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
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