15.33 AVXS-101 in presymptomatic spinal muscular atrophy (SMA)
Bibliographic record
Abstract
Background Onasemnogene abeparvovec (AVXS-101) is a gene-replacement therapy that treats the genetic root cause of SMA, biallelic survival motor neuron 1 gene ( SMN1 ) deletion/mutation. In a phase 1 study, AVXS-101 improved survival and motor function of symptomatic SMA type 1 patients. In SPR1NT ( NCT03505099 ), AVXS-101 is being evaluated in presymptomatic newborns with SMA. Methods SPR1NT is a multicenter, open-label, phase 3 study enrolling ≥27 SMA patients with 2x SMN2 or 3x SMN2 . Asymptomatic infants aged ≤6 weeks receive a one-time, intravenous AVXS-101 infusion. Safety and efficacy are assessed through 18 or 24 months for patients with 2x or 3x SMN2 , respectively. Primary outcomes are independent sitting ≥30 seconds (2x SMN2 ) or assisted standing (3x SMN2 ). Results As of 8 March 2019, 18 infants aged 8–40 days received AVXS-101 (11 female; 8 with 2x SMN2 ; 9 with 3x SMN2 ; 1 with 4x SMN2 ). Among patients with 2x SMN2 , mean CHOP-INTEND at baseline was 44.0 points, which increased by 14.4 points at 3 months (n=7); 6/8 patients scored ≥60 points; 3/8 reached maximum score. 4/8 patients sat unassisted; all ages of sitting milestone achievements were within the WHO range (1st–99th percentile: 3.8–9.2 months). Conclusions Preliminary data from SPR1NT show rapid motor function improvements in presymptomatic SMA patients.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".