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Record W4405897742 · doi:10.1212/wnl.0000000000210268

Safety and Efficacy of IV Onasemnogene Abeparvovec for Pediatric Patients With Spinal Muscular Atrophy

2024· article· en· W4405897742 on OpenAlexaff
Hugh J. McMillan, Giovanni Baranello, Michelle A. Farrar, Craig M. Zaidman, T. Moreno, Liesbeth De Waele, Yuh‐Jyh Jong, Vincent Laugel, Susana Quijano‐Roy, Eugenio Mercuri, Yin‐Hsiu Chien, Volker Straub, Basil T. Darras, Julia Seibert, I. Alecu, F. Freischläger, Francesco Muntoni

Bibliographic record

VenueNeurology · 2024
Typearticle
Languageen
FieldMedicine
TopicNeurogenetic and Muscular Disorders Research
Canadian institutionsChildren's Hospital of Eastern OntarioUniversity of Ottawa
FundersChugai PharmaceuticalInstitut National de la Santé et de la Recherche MédicaleSarepta TherapeuticsEuropean CommissionSanofiPTC TherapeuticsAveXisBiogenAmicus TherapeuticsRegeneron PharmaceuticalsAlexion PharmaceuticalsPfizer
KeywordsSpinal muscular atrophyMedicineAtrophyProgressive muscular atrophyPhysical medicine and rehabilitationPediatricsPhysical therapyInternal medicineAmyotrophic lateral sclerosisDisease

Abstract

fetched live from OpenAlex

BACKGROUND AND OBJECTIVES: Safety and efficacy of IV onasemnogene abeparvovec has been demonstrated for patients with spinal muscular atrophy (SMA) weighing <8.5 kg. SMART was the first clinical trial to evaluate onasemnogene abeparvovec for participants weighing 8.5-21 kg. METHODS: SMART was an open-label, multicenter, phase 3b study conducted across 13 sites in 9 countries (NCT04851873). Symptomatic pediatric participants with SMA (any type; treatment-naïve or had discontinued prior treatment) were stratified into 3 weight cohorts (≥8.5-13, >13-17, and >17-21 kg), administered onasemnogene abeparvovec, and followed for 52 weeks. Corticosteroids were initiated 24 hours before infusion with dose increases in response to adverse events (AEs) and subsequent tapering at investigator discretion. The primary objective was safety. Secondary objective was efficacy (motor function/motor milestones). RESULTS: copies) achieved new motor milestones. DISCUSSION: Onasemnogene abeparvovec safety profile was similar across weight groups in this heterogenous participant population. Frequency and duration of asymptomatic aminotransferase elevations and thrombocytopenia are notable findings. Most participants demonstrated maintenance or improvement of motor function, suggesting clinical benefit for patients with SMA weighing up to 21 kg. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov identifier (NCT04851873, clinicaltrials.gov/study/NCT04851873) submitted April 19, 2021. First participant enrolled on September 8, 2021. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that intravenous onasemnogene abeparvovec is safe in pediatric patients with SMA who weigh 8.5-21 kg.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.143
Threshold uncertainty score0.370

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.272
Teacher spread0.263 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations23
Published2024
Admission routes1
Has abstractyes

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