Nedosiran in Patients With Primary Hyperoxaluria 1: Interim Results From an Extension Trial (PHYOX3)
Bibliographic record
Abstract
Background: Primary hyperoxaluria (PH) is a family of genetic disorders leading to oxalate overproduction, causing calcium oxalate stones and kidney damage, which may result in kidney failure. Nedosiran—an investigational RNA interference (RNAi) therapy in development for treatment of PH—silences hepatic LDH expression encoded by the LDHA gene, which reduces oxalate production. In a 6-month (mo) placebo-controlled pivotal trial (PHYOX2), monthly nedosiran resulted in significantly lower urinary (Uox) and plasma oxalate in PH1 patients. Methods: PHYOX3 (NCT04042402) is an open-label extension trial evaluating long-term safety and efficacy of monthly SC nedosiran in patients with genetically confirmed PH and eGFR ≥ 30 mL/min/1.73 m2 who completed a previous nedosiran trial. This is a 9-mo analysis of PH1 patients from PHYOX2 nedosiran (NEDO|NEDO) and placebo (PLBO|NEDO) arms who rolled into PHYOX3. Results: Both NEDO|NEDO and PLBO|NEDO groups showed substantial reduction in 24-hr Uox, regardless of baseline Uox entering PHYOX2 or PHYOX3 (Figure). The mean Uox reduction was 64.9% and 68.1% for NEDO|NEDO and 55.1% and 60.8% for PLBO|NEDO at the 6-mo and 9-mo visits, respectively. Among the NEDO|NEDO patients, 11 of 13 (85%) and 7 of 7 (100%) achieved normal or near-normal Uox (< 0.6 mmol/24-hr; < 1.3 x ULN) at the 6-mo and 9-mo visits, respectively. Most common drug-related AEs were administration site events; injection site reactions were observed in 3 patients. There were no drug-related SAEs or study discontinuations, or deaths. Conclusions: Nedosiran administration to PH1 patients resulted in significant and persistent reduction of Uox and showed an acceptable safety profile. Analysis of long-term effects on kidney function is ongoing. Funding: Commercial Support - Dicerna Pharmaceuticals, Inc. ( A wholly owned subsidiary of Novo Nordisk A/S)
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".