Atacicept 150 mg Reduces Serum Gd-IgA1, a Biomarker Associated with Long-Term Outcomes in IgA Nephropathy (IgAN): 36W Results from the Ph2b ORIGIN Study
Bibliographic record
Abstract
Background: IgA nephropathy (IgAN), the most common primary glomerulonephritis and a significant contributor to ESRD worldwide, is characterized by elevated serum levels of galactose-deficient immunoglobulin A1 (Gd-IgA1). High Gd-IgA1 levels are associated with greater risk of renal function deterioration. Gd-IgA1 production is driven by the B Lymphocyte Stimulator (BLyS)-A PRoliferation-Inducing Ligand (APRIL) signaling pathway's effect on B cells and plasma cells. Atacicept is a dual anti-BLyS/APRIL fusion protein in clinical development for IgAN treatment. The Ph2b ORIGIN study of atacicept in IgAN met its primary endpoint. The objective of this analysis is to evaluate change in serum Gd-IgA1 quartiles over 36 weeks (w) with atacicept 150mg, the dose being evaluated in a pivotal Ph3 study, vs placebo (PBO). Methods: The randomized, double-blind, PBO controlled Ph2b ORIGIN study included 116 patients (pts) with biopsy-proven IgAN, eGFR ≥30mL/min/1.73m2, and urine protein >0.75g/24h or UPCR >0.75g/g despite optimized renin-angiotensin system blockade. Pts were randomized 2:2:1:2 to atacicept 150, 75, or 25 mg vs PBO SC qw for 36w. At baseline (BL), 4, 12, 24, and 36w, Gd-IgA1 values were assessed and classified into quartiles using cutoffs derived from BL Gd-IgA1 values. Results: Atacicept 150mg (n=30) achieved 64% mean Gd-IgA1 reduction vs 7% for PBO (n=29) at 36w (p<0.001) in pts with BL and 36w data. Atacicept 150mg led to steady Gd-IgA1 reduction to the lowest quartile 1 at 36w in 27/33 pts while most PBO pts transiently increased or decreased by 1 quartile (Figure). In the atacicept 150mg arm, 5/8 pts with BL quartile 4 had reductions to quartile 1 at 36w, while in the PBO arm 8/9 with BL quartile 4 remained in quartile 3 or 4 at 36w. Conclusions: Atacicept 150mg achieved a durable and significant Gd-IgA1 reduction over 36w. Regardless of BL quartile, the vast majority of pts receiving atacicept 150mg for 36w had Gd-IgA1 reductions to the lowest quartiles, which has been associated with greater renal survival. These results provide further evidence supporting atacicept as a potential disease-modifying treatment for IgAN. 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 | 0.002 | 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 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".