Safety and Efficacy of Intravenous Onasemnogene Abeparvovec in Patients with Spinal Muscular Atrophy: Interim Findings from the Phase 3 SMART Study
Bibliographic record
Abstract
Background/Purpose: Clinical trials have demonstrated safety and efficacy of intravenous (IV) onasemnogene abeparvovec (OA) in patients with spinal muscular atrophy (SMA) weighing <8.5 kg. Methods: SMART was a phase 3b study to evaluate the safety, tolerability, and efficacy of IV OA over 52 weeks for patients weighing ≥8.5 to ≤21 kg. Results: Of 24 enrolled patients, 7, 8, and 9 were in the 8.5–13 kg, <13–17 kg, and <17–21 kg weight groups, respectively. 19 discontinued prior nusinersen; 2 discontinued prior risdiplam; 3 were treatment-naïve. No study withdrawals or deaths have occurred. All patients had ≥1 TEAE; 15 (62.5%) had ≥1 SAE; 7 (29%) had SAEs related to OA. 20/24 patients (83.3%) had aminotransferase elevation adverse events; all cases were asymptomatic and managed with prophylactic prednisolone. Transaminase elevations (all Grade 1) were ongoing in 14 patients at the end of study. No bilirubin elevations or Hy's law cases were observed. Steroids were used over a median of 175.0 days. Transient thrombocytopenia was reported in 17/24 patients (70.8%); all resolved with no reported bleeding events. 3/24 patients (13%) had cardiac AEs (all unrelated to OA). No events of thrombotic microangiopathy or dorsal root ganglionopathy were observed. Frequency/severity of AEs were similar across weight groups. Motor function (RULM and motor milestones) was maintained or improved for most patients. Mean (SD) change from baseline at Week 52 was 2.0 (4.0) for RULM. By Week 52, three patients achieved standing with assistance, one patient achieved independent standing, and one patient achieved walking with assistance. Conclusion: The safety of onasemnogene abeparvovec in SMART was consistent with previously reported findings. Most patients experienced transaminase elevations with no difference between weight groups; all cases were asymptomatic and managed with steroids. Most patients maintained or improved motor function, suggesting clinical benefit of IV OA for heavier patients with SMA. Publication History Article published online: 13 November 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".