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Final phase III analyses found that atacicept and sibeprenlimab slowed the decline in kidney function in adults with IgA nephropathy compared with placebo. Both medicines received accelerated FDA approval based on earlier proteinuria results; the new findings are intended to confirm clinical benefit and support traditional approval.
Atacicept and sibeprenlimab slowed the decline in kidney function compared with placebo in final phase III analyses involving adults with IgA nephropathy, according to results presented October 24 at the American Society of Nephrology’s Kidney Week meeting. The findings address a condition of the drugs’ accelerated FDA approvals: confirming that treatment slows kidney-function loss, not only reducing protein in urine.
In the ORIGIN trial, 431 adults with biopsy-confirmed IgA nephropathy received weekly subcutaneous atacicept, 150 milligrams, or placebo. At week 52, mean eGFR change was -0.11 milliliters per minute per 1.73 square meters in the atacicept group and -5.69 in the placebo group, a between-group difference of 5.58. Through week 104, the annualized eGFR slope was -0.60 with atacicept and -5.60 with placebo, a difference of 5.00 milliliters per minute per 1.73 square meters per year.
A composite measure of kidney-disease progression through week 104 occurred in 5.1% of atacicept recipients and 17.8% of placebo recipients. The trial investigators reported a hazard ratio of 0.24, corresponding to a 76% lower risk in the atacicept group. The composite included sustained eGFR decline, very low eGFR, dialysis, transplantation or death. No atacicept recipients reached dialysis, received a transplant or died; seven placebo recipients experienced one of those outcomes.
In the VISIONARY trial, 510 participants were assigned to sibeprenlimab, 400 milligrams every four weeks, or placebo. Over 104 weeks, annualized eGFR slope was 0.3 milliliters per minute per 1.73 square meters per year with sibeprenlimab and -4.2 with placebo, a difference of 4.5. The reported treatment difference in eGFR change from baseline to 24 months was 9.2 milliliters per minute per 1.73 square meters.
A kidney-outcome composite occurred in one sibeprenlimab patient (0.4%) and 28 placebo patients (11.2%). The study reported a hazard ratio of 0.029 and an adjusted difference of -10.8 percentage points. The composite included sustained doubling of serum creatinine, a sustained 40% eGFR reduction, very low eGFR or starting kidney-replacement therapy. The trials were published simultaneously in the New England Journal of Medicine.
Kidney Function Results Address FDA Conditions
The results matter because they test whether the medicines can slow loss of kidney function, a longer-term outcome that was not established by the earlier evidence supporting accelerated approval. Those approvals were based on interim findings showing reduced proteinuria. The final analyses provide trial evidence addressing the FDA’s requirement for confirmation of benefit to maintain approval, though a regulatory decision on traditional approval is not reported here.
IgA nephropathy can progress to kidney failure, and the trial investigators emphasized the importance of reducing the rate of eGFR decline. At a press conference, Dana V. Rizk of the University of Alabama at Birmingham said the 2025 KDIGO guidelines set a treatment aim of lowering eGFR decline to below 1 milliliter per minute per 1.73 square meters per year, described as close to the normal physiological rate. The trial averages indicate a difference from placebo; they do not establish that every patient will respond similarly or avoid kidney failure.
The findings also give clinicians and patients longer-term comparative data for two treatments that act on immune pathways linked to IgA production. Safety and individual treatment decisions remain relevant alongside the kidney-function results.
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From Proteinuria to Kidney Outcomes
IgA nephropathy is an immune-mediated kidney disease. The two medicines target related but distinct parts of the immune system: atacicept is a TACI-Fc fusion protein that targets BAFF and APRIL, while sibeprenlimab is an antibody that selectively inhibits APRIL. Both approaches are intended to affect pathways involved in IgA production.
The FDA granted both agents accelerated approval based on interim trial findings showing reduced proteinuria, the presence of excess protein in urine. Continued approval was contingent on final analyses confirming slowed kidney-function decline. The new ORIGIN and VISIONARY results are those confirmatory efficacy findings, and the companies are seeking traditional approval based on the data.
Approval and Long-Term Outcomes Remain Open
The reported findings do not establish whether the FDA will grant traditional approval to either medicine or when the agency might act. The source report says the results will be submitted to support full approval; it does not provide an FDA review timetable or decision.
The trials followed participants for up to 104 weeks, so outcomes beyond that period remain uncertain. The studies also used different kidney-outcome composites and dosing schedules, meaning their results should not be treated as a direct comparison of the two drugs. Trial averages do not show how an individual patient will fare, and continued monitoring of effectiveness and safety is relevant as use expands.
FDA Submissions and Ongoing Follow-Up
ORIGIN investigator Jonathan Barratt said the atacicept findings would be submitted to the FDA to support full approval. Otsuka Pharmaceutical said VISIONARY’s sibeprenlimab findings had been submitted for traditional approval. FDA review and any agency decisions are the next regulatory milestones identified in the report; no decision date was provided.
Barratt also said participants assigned to placebo in ORIGIN were being moved onto atacicept. Further follow-up and regulatory review will help clarify how the trial findings inform longer-term treatment and safety assessments.
Key Questions
What did the final trials find?
Both trials reported slower average decline in eGFR, a measure of kidney function, among participants receiving the study drug than among those receiving placebo over the reported follow-up.
Are the drugs fully approved by the FDA?
The source report says both medicines received accelerated FDA approval based on earlier proteinuria findings. The final trial results address a condition of those approvals, and traditional approval is being sought; no FDA decision on that status is reported.
Can the results show which drug works better?
No. Atacicept and sibeprenlimab were tested in separate trials with different participants and kidney-outcome definitions. The results are not a head-to-head comparison.
What safety findings were reported?
In ORIGIN, adverse events occurred in 74.8% of atacicept recipients and 78.0% of placebo recipients; serious adverse events occurred in 7.0% and 15.4%, respectively. In VISIONARY, researchers said overall adverse events, including infections, were similar between groups, and no deaths occurred. These are trial findings, not a prediction of an individual patient’s experience.
Source: rss
