Efficacy and safety of onasemnogene abeparvovec in children with spinal muscular atrophy type 1: real-world evidence from 6 infusion centres in the United Kingdom

Gowda, Vasantha; Atherton, Mark; Murugan, Archana; Servais, Laurent; Sheehan, Jennie; Standing, Emma; Manzur, Adnan; Scoto, Mariacristina; Baranello, Giovanni; Munot, Pinki; McCullagh, Gary; Willis, Tracey; Tirupathi, Sandya; Horrocks, Iain; Dhawan, Anil; Eyre, Michael; Vanegas, Maria; Fernandez-Garcia, Miguel A.; Wolfe, Amy; Pinches, Laura; Illingworth, Marjorie; Main, Marion; Abbott, Lianne; Smith, Hayley; Milton, Emily; D’Urso, Sarah; Vijayakumar, Kayal; Marco, Silvia Sanchez; Warner, Sinead; Reading, Emily; Douglas, Isobel; Muntoni, Francesco; Ong, Min; Majumdar, Anirban; Hughes, Imelda; Jungbluth, Heinz; Wraige, Elizabeth

doi:10.1016/j.lanepe.2023.100817

Cited by 5 publications

(2 citation statements)

References 34 publications

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“…There is a paucity of data on safety and efficacy outcomes of onasemnogene abeparvovec when administered to patients older than 2 years of age. Real-world evidence of 21 patients aged ≥2 years at onasemnogene abeparvovec infusion reported an estimated 3.8-point gain in CHOP-INTEND scores after gene therapy (follow-up duration not reported) ( 25 ). A separate study ( 22 ) reported an increase of 5.1 points in mean CHOP-INTEND scores from baseline to 12 months (47.1 vs. 52.2 points, respectively) in 19 SMA type 1 patients with ≥2 SMN2 copies aged >2 years at onasemnogene abeparvovec treatment, which is similar to the 7.7-point increase reported here (46.0 vs. 53.7 points from baseline to 12 months, respectively).…”

Section: Discussionmentioning

confidence: 99%

Motor and neurocognitive profiles of children with symptomatic spinal muscular atrophy type 1 with two copies of SMN2 before and after treatment: a longitudinal observational study

Bitetti,

Manna,

Stella

et al. 2024

Front. Neurol.

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IntroductionSpinal muscular atrophy (SMA) is a neurodegenerative disease caused by mutations in the survival motor neuron 1 (SMN1) gene. In clinical studies, gene replacement therapy with onasemnogene abeparvovec (formerly AVXS-101, Zolgensma®, Novartis) was efficacious in improving motor functioning in children with SMA. However, its effects on cognitive and language skills are largely unknown.MethodsThis longitudinal observational study evaluated changes in motor and neurocognitive functioning over a 1-year period after administration of onasemnogene abeparvovec in 12 symptomatic SMA type 1 patients with two copies of SMN2 aged 1.7–52.6 months at administration. Motor functioning was measured using the Children's Hospital of Philadelphia Infant Test for Neuromuscular Disorders (CHOP-INTEND) while neurocognitive assessment was measured using Griffiths III. Motor milestones and language ability were also assessed at each timepoint.Results and discussionStatistically significant increases in median CHOP-INTEND scores from baseline were observed at 1, 3, 6, and 12 months after onasemnogene abeparvovec administration (all p ≤ 0.005). Most (91.7%) patients were able to roll over or sit independently for >1 min at 12 months. Significant increases in the Griffiths III Foundations of Learning, Language and Communication, Eye and Hand Coordination, and Personal-Social-Emotional subscale scores were observed at 12-months, but not in the Gross Motor subscale. Speech and language abilities progressed in most patients. Overall, most patients showed some improvement in cognitive and communication performance after treatment with onasemnogene abeparvovec in addition to significant improvement in motor functioning and motor milestones. Evaluation of neurocognitive function should be considered when assessing the global functioning of patients with SMA.

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Section: Discussionmentioning

confidence: 99%

Motor and neurocognitive profiles of children with symptomatic spinal muscular atrophy type 1 with two copies of SMN2 before and after treatment: a longitudinal observational study

Bitetti,

Manna,

Stella

et al. 2024

Front. Neurol.

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“…In this issue of The Lancet Regional Health–Europe , Gowda and colleagues now report on the treatment results of the nationwide use of OA in the UK in patients older than 2 years and with body weights over 13.5 kg. 7 The data was collected as part of an observational study conducted at all centers authorized to treat SMA in the UK. Ninety-nine SMA (45 of which were treatment-naïve) were treated with OA (median age at treatment: 10 [range, 0.6–89] months; median weight: 7.86 [range, 3.2–20.2] kg; duration of follow-up: 3–22 months).…”

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confidence: 99%