TL;DR
Final analyses from the phase III ORIGIN and VISIONARY trials found that atacicept and sibeprenlimab slowed the decline in kidney function among adults with IgA nephropathy compared with placebo. Both drugs had received accelerated FDA approval based on earlier proteinuria results; the new findings are intended to support full approval.
Final phase III results show that atacicept and sibeprenlimab slowed the decline in kidney function compared with placebo in adults with IgA nephropathy, a kidney disease that can progress to kidney failure. The findings from the ORIGIN and VISIONARY trials address a condition of the drugs’ accelerated FDA approvals and are being used to seek traditional approval.
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In the 431-person ORIGIN trial, adults with biopsy-confirmed IgA nephropathy received weekly injections of atacicept 150 mg or placebo. At week 52, mean eGFR change was -0.11 mL/min/1.73 m² with atacicept and -5.69 with placebo. Over 104 weeks, the annualized eGFR slope was -0.60 versus -5.60 mL/min/1.73 m² per year, respectively, a difference of 5.00 (95% CI 3.55-6.45; P<0.001).
By week 104, the trial’s composite kidney-disease progression outcome occurred in 5.1% of atacicept recipients and 17.8% of placebo recipients. The outcome included sustained eGFR decline or low eGFR, dialysis, transplant, or death. Researchers reported a 76% lower risk with atacicept (HR 0.24, 95% CI 0.12-0.48). No atacicept recipients progressed to dialysis, transplant, or death; seven placebo recipients did.
In VISIONARY, which randomized 510 participants, 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 (95% CI 3.6-5.4; P<0.001). A composite kidney endpoint occurred in one participant receiving sibeprenlimab and 28 receiving placebo. The researchers reported a 97% lower risk (HR 0.029, 95% CI 0.004-0.214); no deaths occurred, and overall adverse events, including infections, were similar between groups.
Kidney Function Over Two Years
The results address whether the drugs’ earlier reductions in proteinuria were accompanied by a slower loss of kidney function, a key measure for people at risk of progressive IgA nephropathy. The two trials found a substantial separation in eGFR trends between treatment and placebo groups over two years. That may matter to patients and clinicians weighing options intended to delay kidney failure.
The trial outcomes and follow-up periods are not identical, so their effect estimates should not be read as a direct comparison between the drugs. The findings also do not establish that either treatment prevents kidney failure for every patient or show how benefits and risks will compare in broader, longer-term use. The results are evidence for regulatory review, not a guarantee of full approval.
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From Accelerated Approval to Full Review
Both medicines received accelerated FDA approval after interim trial findings showed reductions in proteinuria, a marker of kidney damage. Under that pathway, the sponsors were required to confirm clinical benefit in later analyses for continued approval. ORIGIN and VISIONARY supplied the kidney-function results needed to address that requirement.
Atacicept is a TACI-Fc fusion protein that targets BAFF and APRIL, signaling proteins involved in immune activity. Sibeprenlimab is an antibody that inhibits APRIL. The trials used different dosing schedules and different definitions for their composite kidney endpoints. At the Kidney Week meeting, researchers said the studies were published simultaneously in the New England Journal of Medicine.
Approval and Longer-Term Outcomes
The reported findings do not settle whether the FDA will grant traditional approval to either drug. The source report says the ORIGIN findings will be submitted to the agency, while Otsuka Pharmaceutical said VISIONARY results had been submitted. The FDA’s review timetable and decisions were not provided.
The trial reports described outcomes through 104 weeks, but longer-term effectiveness and safety remain less clear from the information available here. The studies also used different kidney endpoints, and their results do not establish which drug is more effective. Individual treatment decisions and how the drugs may fit alongside other care are not answered by these trial summaries.
FDA Review and Trial Follow-Up
The next regulatory step is FDA assessment of the final trial evidence for full approval. Sponsors and investigators may provide further details as review proceeds, but no decision date was reported. In ORIGIN, Barratt said participants assigned to placebo were being moved onto atacicept after the findings were reviewed.
Further follow-up will help clarify whether the eGFR differences persist beyond two years and how safety and kidney outcomes develop over time. Until those data and FDA decisions are available, the confirmed news is the trial results—not a change in either drug’s approval status.
Key Questions
What did the trials find?
Both trials found a slower decline in eGFR, a measure of kidney function, among participants receiving the study drug than among those receiving placebo over 104 weeks.
Are the drugs fully FDA-approved?
The source report says both had accelerated FDA approval based on earlier proteinuria findings. The new analyses are intended to support traditional approval; the report does not state that the FDA has granted it.
Do the results show one drug works better?
No direct comparison was conducted. ORIGIN and VISIONARY involved separate trials with different participants and endpoint definitions, so their results cannot establish which drug is more effective.
Were serious safety concerns reported?
In ORIGIN, serious adverse events were reported in 7.0% of atacicept recipients and 15.4% of placebo recipients. In VISIONARY, researchers said overall adverse events, including infections, were similar between groups and no deaths occurred. These trial summaries do not resolve longer-term safety.
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