Long-Term Results from the ORIGIN Phase 2b Study of Atacicept for the Treatment of IgA Nephropathy (IgAN)
Bibliographic record
Abstract
Background: B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL) play key roles in IgAN pathogenesis. Atacicept is a humanized TACI-Fc fusion protein that inhibits both BAFF and APRIL and is self-administered at home by subcutaneous injection. The ORIGIN Phase 2b study met the primary endpoint with a statistically significant and clinically meaningful UPCR reduction compared to placebo at 24 weeks, with a further reduction and eGFR stabilization through 36 weeks. This analysis reports 96-week results from the open-label extension (OLE). Methods: Participants with IgAN who received atacicept or placebo in the 36-week Phase 2b, randomized, blinded study period were enrolled in an OLE and received atacicept 150 mg for an additional 60 weeks. Key efficacy outcomes were changes in galactose-deficient IgA1 (Gd-IgA1), percentage of participants with hematuria, UPCR, and eGFR over 96 weeks. Long-term safety data were also evaluated. Results: There were 113 participants who received ≥1 atacicept dose. Over 96 weeks, there were sustained reductions (mean ±SE) in Gd-IgA1 (-65.9% ±1.7%), the percentage of participants with hematuria (-75.0%, 95% CI -87.3, -58.8; in participants with baseline hematuria), and UPCR (-52.2% ±4.7%). Importantly, long-term eGFR was maintained near baseline levels with a mean annualized slope of -0.6 ±0.5 mL/min/1.73m2/year at 96 weeks (Figure). Safety data showed atacicept was generally well tolerated. Conclusion: Gd-IgA1, hematuria, and UPCR reductions with eGFR stabilization through 96 weeks demonstrate that atacicept offers a potentially safe, long-term, disease-modifying treatment for IgAN. Specifically, the conversion of an eGFR profile in patients with IgAN from one of steady decline to one representative of the general population without kidney disease1 supports the potential of atacicept to decrease the high lifetime risk of kidney failure in patients with IgAN. 1. Baba M. PLoS One 2015. Funding: Commercial Support - Vera Therapeutics, Inc.
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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 | 0.010 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 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".