Tofersen in adults with SOD1-ALS: phase 3 VALOR trial and open-label extension results
Bibliographic record
Abstract
VALOR was a Phase 3, placebo-controlled trial to evaluate the clinical efficacy and safety of tofersen in adults with ALS and a confirmed SOD1 mutation (SOD1-ALS). Participants were randomised 2:1 to tofersen 100 mg (3 doses ~2 weeks apart, then 5 doses every 4 weeks) or placebo administered intrathecally. The primary endpoint was change from baseline to Week 28 in the ALS Functional Rating Scale-Revised (ALSFRS-R) total score. Key secondary endpoints included CSF total SOD1 concentration and other clinical outcome measures. Participants could continue in an open-label extension (OLE) upon completion of VALOR. 108 total participants were enrolled (tofersen [n=72], placebo [n=36]). VALOR did not achieve statistical significance on the ALSFRS-R at Week 28, the primary endpoint. Tofersen administration led to robust reductions in CSF total SOD1 protein and plasma neurofilament light chain (NfL) at Week 28 compared to baseline. Trends favoring tofersen were seen across clinical outcome measures of respira- tory function, muscle strength, and quality of life. These effects became more apparent with longer-term follow-up in the OLE, particularly with earlier tofersen initiation. Most adverse events were mild to moderate in severity. Serious neurologic events, including myelitis (2%), were seen in tofersen-treated participants. Study sponsored by Biogen.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".