Atacicpet, Sibeprenlimab Halt Decline In Kidney Function In IgA Nephropathy

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Final analyses from the ORIGIN and VISIONARY phase III trials found slower loss of kidney function with atacicept and sibeprenlimab than with placebo in adults with IgA nephropathy. The results, presented at the American Society of Nephrology’s Kidney Week meeting and published in the New England Journal of Medicine, are intended to support traditional FDA approval; the drugs had previously received accelerated approval based on proteinuria reductions.

Final analyses from two phase III trials found that atacicept and sibeprenlimab slowed the decline in kidney function in adults with IgA nephropathy compared with placebo, providing the kidney-outcome evidence required under their accelerated FDA approvals. The results were presented at the American Society of Nephrology’s Kidney Week meeting and published in the New England Journal of Medicine; they are expected 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 between-group difference of 5.58 mL/min/1.73 m². Through week 104, the annualized eGFR slope was -0.60 mL/min/1.73 m² per year with atacicept and -5.60 with placebo. The reported difference was 5.00 mL/min/1.73 m² per year (95% CI 3.55-6.45; P<0.001).

A trial-defined composite measure of kidney-disease progression occurred in 5.1% of atacicept recipients and 17.8% of placebo recipients through week 104. The investigators reported a 76% lower risk with atacicept (hazard ratio 0.24, 95% CI 0.12-0.48; P<0.001). No atacicept recipients progressed to dialysis, transplantation or death, compared with seven participants in the placebo group. Adverse events were reported in 74.8% and 78.0% of the two groups, respectively; serious adverse events occurred in 7.0% and 15.4%.

In the 510-person VISIONARY trial, patients received sibeprenlimab every four weeks or placebo. Over 104 weeks, the annualized eGFR slope 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). The least-squares mean difference in eGFR change from baseline to 24 months was 9.2 mL/min/1.73 m² (95% CI 7.1-11.4; P<0.001). A composite kidney endpoint occurred in one patient receiving sibeprenlimab (0.4%) and 28 receiving placebo (11.2%). Researchers reported no deaths and similar overall adverse-event rates between groups.

Kidney Outcomes Shape FDA Review

The results address a specific requirement of both drugs’ accelerated approvals. Those approvals were based on interim findings showing reductions in proteinuria, a measure of protein in urine. The final analyses tested whether treatment also slowed decline in kidney function, a more direct clinical outcome. Trial results can support regulatory review, but they do not by themselves establish that the FDA has granted traditional approval.

IgA nephropathy can progressively damage the kidneys, and the pace of eGFR loss helps clinicians track that decline. The trial investigators cited the 2025 KDIGO guidelines’ treatment aim of reducing eGFR loss to below 1 mL/min/1.73 m² per year. The reported treatment-group slopes were near that level in these studies, while the placebo groups declined more rapidly. Comparisons across separate trials should be made cautiously: their participants, endpoints and designs differ.

From Proteinuria to Kidney Function

IgA nephropathy is an immune-mediated kidney disease. Atacicept is a TACI-Fc fusion protein that targets BAFF and APRIL, signaling proteins involved in immune activity. Sibeprenlimab is an antibody that selectively inhibits APRIL. Both approaches are intended to reduce disease-related immune activity, though their targets and dosing schedules differ.

The FDA granted the drugs accelerated approval after interim trial findings showed reduced proteinuria. Under the approval terms described in the report, the sponsors needed final trial analyses confirming a slower decline in kidney function. The ORIGIN and VISIONARY results were presented at the American Society of Nephrology Kidney Week meeting and published at the same time in the New England Journal of Medicine.

Approval and Longer-Term Effects

The report says the findings will be submitted to the FDA to support full approval, and that Otsuka Pharmaceutical said the sibeprenlimab results had been submitted for traditional approval. The material does not state that the FDA has completed either review or granted traditional approval. It also does not provide a decision date.

The trials report outcomes over 104 weeks, so the durability of the effects beyond that period is not established by these results. Although adverse events were reported during the trials, the findings provided here do not settle how benefits and risks will compare across broader patient populations or in routine care. The reported risk reductions refer to each trial’s defined composite endpoint and should not be read as a direct comparison between the two medicines.

FDA Review and Continued Follow-Up

The next regulatory milestone is FDA review of the submitted final results and any related applications for traditional approval. The report gives no timetable for agency decisions. Trial follow-up and further reporting may clarify how kidney-function outcomes develop over longer periods, while clinicians and regulators assess the results alongside safety data and other available evidence.

Key Questions

What did the final trials find?

Both trials found slower eGFR decline with the study drug than with placebo over 104 weeks. ORIGIN tested atacicept; VISIONARY tested sibeprenlimab. Their results come from separate trials and are not a head-to-head comparison.

Do these results mean the drugs have full FDA approval?

No. The report says the findings are being used to support traditional approval applications. It does not report an FDA decision granting full approval.

How did the drugs differ?

Atacicept targets BAFF and APRIL and was given weekly by injection in ORIGIN. Sibeprenlimab selectively inhibits APRIL and was given every four weeks in VISIONARY.

Were safety findings different from placebo?

In ORIGIN, adverse events occurred in 74.8% of atacicept recipients and 78.0% of placebo recipients; serious events occurred in 7.0% and 15.4%. In VISIONARY, researchers reported similar overall adverse-event incidence between groups and no deaths. These trial findings do not determine an individual patient’s risks.

Source: rss