P026: Interim analysis of the efficacy and safety of weekly intravenous tividenofusp alfa in mucopolysaccharidosis type II: A phase 1/2 study
Bibliographic record
Abstract
Introduction: Tividenofusp alfa is an investigational iduronate-2-sulfatase fusion protein engineered for CNS delivery to address cognitive and behavioral decline in mucopolysaccharidosis type II (MPS II; OMIM 309900) while optimizing somatic disease control.Methods: A single-arm, 24-week, phase 1/2 study (NCT04251026) with extension enrolled males ≤18 years with MPS II.Participants received 15 mg/kg tividenofusp alfa with or without prior dose escalation via weekly intravenous infusion.Biomarker endpoints included cerebrospinal fluid (CSF) heparan sulfate (HS), serum neurofilament light chain (NfL), and urine HS.Clinical endpoints included safety assessment, cognitive measures (Bayley Scales of Infant and Toddler Development, third edition [BSID-III]/Kaufman Assessment Battery for Children, second edition [KABC-II]), adaptive behavior, auditory brainstem responses, and abdominal imaging.Interim data from 1 March 2024, except serum NfL and urine HS (1 September 2023 cutoff), are summarized.Results: Participants (N=43) had a median (range) age of 4.7 (0.3-12.6) years; 93.0% were neuronopathic and 65.1% had prior enzyme replacement therapy (ERT).As expected for ERT, a majority reported infusion-related reactions, which were manageable and decreased in frequency over time.Mean CSF HS was reduced 90.9% from baseline to Week 24; reductions were sustained through Weeks 49 (-90.4%),104 (-91.1%) and 153 (-89.3%),all p<0.0001, most below the upper limit of the normal range.Mean urine HS was reduced 84.6% from baseline to Week 24; reductions were sustained through Weeks 49 (-86.5%),104 (-78.2%) and 129 (-80.1%),all p<0.0001.Serum NfL (geometric mean) was significantly reduced by Week 61 (-41.1%), with further reduction at Weeks 104 (-70.4%) and 129 (-81.5%;all within normal range), all p≤0.0001.As of the last visit, 67.6% of participants had improved/unchanged cognitive (BSID-III/ KABC-II) age equivalent scores relative to baseline, including nearly all participants aged <4 years at treatment initiation.Updated results will be presented.Conclusion: Treatment with tividenofusp alfa was well tolerated, resulted in substantial sustained reductions in CSF and urine HS, lowered serum NfL, and improved or unchanged cognitive (BSID-III/KABC-II) age equivalent scores in males ≤18 years with MPS II.
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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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.003 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.005 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
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".