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Final analyses of the ORIGIN and VISIONARY phase III trials found that atacicept and sibeprenlimab slowed the decline in kidney function compared with placebo in adults with IgA nephropathy. Both drugs had received accelerated FDA approval based on proteinuria results; the new kidney-function findings are intended to support traditional approval.
Final analyses of two phase III trials found that atacicept and sibeprenlimab slowed kidney-function decline compared with placebo in adults with IgA nephropathy, meeting a key requirement attached to the drugs’ accelerated FDA approvals. The results, presented October 24 at the American Society of Nephrology Kidney Week meeting and published in the New England Journal of Medicine, are intended to support applications for traditional approval.
In the 431-person ORIGIN trial, participants received weekly atacicept injections or placebo. At week 52, mean eGFR change was -0.11 mL/min/1.73 m² with atacicept and -5.69 with placebo, a difference of 5.58. Over 104 weeks, the annualized eGFR slope was -0.60 mL/min/1.73 m² per year with atacicept and -5.60 with placebo, a between-group difference of 5.00.
Through week 104, the trial’s composite measure of kidney-disease progression occurred in 5.1% of atacicept recipients and 17.8% of placebo recipients. The investigators reported a 76% lower risk with atacicept. The composite included sustained eGFR decline of at least 30%, sustained eGFR below 15, long-term dialysis, transplant or death. No atacicept recipient progressed to dialysis, transplant or death; seven such events occurred in the placebo group.
In the 510-person VISIONARY trial, the annualized eGFR slope over 104 weeks was 0.3 mL/min/1.73 m² per year with sibeprenlimab and -4.2 with placebo, a difference of 4.5. The least-squares mean difference in eGFR change from baseline to 24 months was 9.2 mL/min/1.73 m². A composite kidney-endpoint event occurred in one patient receiving sibeprenlimab and 28 receiving placebo. Researchers reported a 97% lower risk of that endpoint, which included sustained creatinine doubling, a sustained 40% eGFR reduction, very low eGFR or starting kidney-replacement therapy.
Safety findings were broadly similar between groups in VISIONARY, including for infections, and no deaths occurred. In ORIGIN, adverse events were reported in 74.8% of atacicept recipients and 78.0% of placebo recipients; serious adverse events occurred in 7.0% and 15.4%, respectively. These are trial findings and do not establish that every patient will have the same benefit or risks.
Kidney-function results support approval
The results address an evidence gap left by the drugs’ accelerated approvals. Those approvals were based on interim findings showing reductions in proteinuria, a marker of kidney injury. The final analyses tested whether treatment also slowed loss of kidney function, the outcome the FDA required the trials to confirm for continued approval.
The reported eGFR slopes in the placebo groups were substantially more negative than those in the treatment groups during the study period. eGFR estimates how well the kidneys filter blood; its rate of change can help show whether kidney function is declining. The findings may matter to people with IgA nephropathy who remain at risk of progression despite existing care, but the trials’ results should not be read as a guarantee of an individual outcome.
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Two trials address approval conditions
IgA nephropathy is an immune-mediated kidney disease. Atacicept targets BAFF and APRIL, two cytokines involved in B-cell activity. Sibeprenlimab is an antibody that selectively inhibits APRIL, with the aim of reducing IgA and galactose-deficient IgA1 levels.
The trials studied different medicines and used different composite kidney endpoints, so their risk-reduction figures should not be treated as a direct comparison between the drugs. ORIGIN tested weekly 150-mg atacicept in adults with biopsy-confirmed disease. VISIONARY tested 400-mg sibeprenlimab every four weeks. Both compared treatment with placebo over a 104-week period.
At the meeting, University of Alabama at Birmingham researcher Dana V. Rizk cited the 2025 KDIGO guidelines’ treatment aim of bringing eGFR decline below 1 mL/min/1.73 m² per year, described as close to the normal physiological rate. That target provides clinical context for the trial slopes; it is not itself a result proving either drug meets the goal for every patient.
FDA decisions and longer-term outcomes
The reported results do not establish whether the FDA will grant traditional approval, when it might decide, or whether regulators will request additional evidence. The source report said the findings would be submitted to support atacicept’s full approval; Otsuka Pharmaceutical said the sibeprenlimab findings had been submitted for traditional approval.
The trials report outcomes through 104 weeks, so the available information does not show how long the kidney-function effects persist beyond that period. The reported summaries also do not resolve how the medicines compare directly with one another or how their benefits and risks may vary in routine care over longer follow-up.
Submissions and follow-up continue
The next regulatory step is FDA review of the trial evidence submitted for traditional approval. The source material does not provide a decision date. ORIGIN participants who had been assigned placebo are being offered atacicept, according to Barratt; further follow-up may provide additional information about treatment outcomes after the controlled comparison.
For both drugs, clinicians and patients will need to weigh the full evidence, including longer-term kidney outcomes and safety, as regulatory review proceeds. The results reported so far establish trial differences over the study period, not the eventual approval outcome or the experience of every person with IgA nephropathy.
Key Questions
What did the final trials find?
Both trials reported slower eGFR decline with active treatment than with placebo over 104 weeks. The trials studied different drugs and populations, so their results are not a head-to-head comparison.
Why do these findings matter for FDA approval?
The drugs received accelerated FDA approval based on interim proteinuria findings. The final kidney-function analyses were required to confirm that treatment slowed decline and are intended to support traditional approval.
How did the drugs perform on the trial endpoints?
In ORIGIN, kidney-disease progression occurred in 5.1% of atacicept recipients and 17.8% of placebo recipients through week 104. In VISIONARY, the composite kidney endpoint occurred in one sibeprenlimab recipient and 28 placebo recipients.
Have the drugs received traditional FDA approval?
The source report describes accelerated approvals and says the final findings were submitted or would be submitted to support traditional approval. It does not report an FDA decision on traditional approval.
How long were patients followed?
The reported final trial analyses covered up to 104 weeks. The source material does not provide longer-term results beyond that period.
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