Long‐Term Efficacy and Tolerability of Pegzilarginase in Arginase 1 Deficiency: Results of Two International Multicentre Open‐Label Extension Studies
Bibliographic record
Abstract
Arginase 1 deficiency (ARG1-D) is an autosomal recessive urea cycle disorder characterised by chronic hyperargininaemia, progressive spasticity, loss of mobility, and cognitive dysfunction. Standard of care (SOC), based on dietary protein restriction, rarely prevents progression. Pegzilarginase, a recombinant human enzyme, is the first approved disease-modifying therapy. We report outcomes from Study 102A (n = 14; up to 5 years) and the PEACE long-term extension (LTE) (n = 31; up to 3 years). Weekly pegzilarginase was administered with SOC. Outcomes included functional mobility (2-/6-minute walk tests [2MWT/6MWT], Gross Motor Function Measure [GMFM] D/E), spasticity (Modified Ashworth Scale [MAS]), plasma arginine, guanidino compounds, and safety. In PEACE, LTE arms were named according to initial 24-week double-blind treatment: placebo-pegzilarginase or pegzilarginase-pegzilarginase. Of 39 evaluable participants, 37 (95%) met composite response or achieved maximum score in ≥ 1 motor function domain. In 102A, mean 6MWT improved to 68.2 m (+19%; n = 12); GMFM-D/E increased by 2.7/3.7. In PEACE (pegzilarginase-pegzilarginase; placebo-pegzilarginase), 2MWT improved to 16.5 m (+25%; n = 6) and 13.5 m (+16%; n = 2); GMFM-D/E improved by 4.3/6.0 (n = 6) and 5.3/11.3 (n = 3). Spasticity improved in 21/25 (84%), with 12 reaching MAS 0 (no spasticity). Pegzilarginase sustained plasma arginine control: in 102A, means were 118 μmol/L at Week 192 (n = 9); in PEACE, < 115 μmol/L through Week 96 (n = 11). Guanidinoacetic acid normalised; N-acetylarginine approached normal; argininic acid and α-keto-δ-guanidinovaleric acid declined by > 50%. Most adverse events were mild/moderate; no treatment-related discontinuations or persistent antibodies occurred. Pegzilarginase produced sustained improvements in mobility, spasticity and biochemical control, supporting early intervention, long-term use and disease modification in ARG1-D.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".