— Final data from ORIGIN and VISIONARY trials pave way for full FDA approvals
October 24, 2026 • 4 min read
DENVER -- Two IgA nephropathy drugs -- atacicept (Trutakna) and sibeprenlimab injection (Voyxact) -- showed they were able to slow kidney function decline in final phase III trial efficacy analyses.
Ataciceptopens in a new tab or window and sibeprenlimabopens in a new tab or window were granted accelerated FDA approval based on interim trial findings that showed a reduction in proteinuria in adults with IgA nephropathy. As a condition of the accelerated approvals, both agents had to confirm slowed decline of kidney function in their final trial analyses for continued approval.
In the ORIGINopens in a new tab or window trial, the mean change in eGFR was -0.11 mL/min/1.73 m² in the atacicept group and -5.69 mL/min/1.73 m² in the placebo group at week 52 (mean difference 5.58 mL/min/1.73 m², 95% CI 3.680-7.48, P<0.001).
Through week 104, the mean annualized eGFR slope was -0.60 mL/min/1.73 m² per year with atacicept and -5.60 mL/min/1.73 m² per year with placebo (difference 5.00 mL/min/1.73 m² per year, 95% CI 3.55-6.45, P<0.001), according Jonathan Barratt, PhD, of the University of Leicester in England.
"If you hadn't exposed them to an atacicept, they would have lost 12 mL of kidney function in 2 years, which is perhaps the highest rate of loss of kidney function we've seen in any IgA nephropathy trial in a placebo group," Barratt said at the American Society of Nephrology Kidney Weekopens in a new tab or window annual meeting.
As for the VISIONARYopens in a new tab or window trial, the annualized eGFR slope over 104 weeks was 0.3 mL/min/1.73 m² per year with sibeprenlimab and -4.2 mL/min/1.73 m² per year with placebo (between-group difference 4.5 mL/min/1.73 m² per year, 95% CI 3.6-5.4, P<0.001).
The least-squares mean treatment difference for the change in eGFR from baseline to 24 months was 9.2 mL/min/1.73 m² (95% CI 7.1-11.4, P<0.001), reported Dana V. Rizk, MD, of the University of Alabama at Birmingham, and colleagues.
Both trials were simultaneously published in the New England Journal of Medicine.
"IgA nephropathy is an immune-mediated kidney disease that seems to have a more guarded prognosis than initially thought," noted Rizk during a press conference. "According to the 2025 KDIGO guidelinesopens in a new tab or window, treatment should aim to reduce the rate of eGFR decline to below 1 mL/min/1.73 m² per year, effectively matching the normal physiological rate of decline."
Barratt emphasized that "we must get the rate of loss of kidney function down to what we see in healthy individuals -- less than 1 mL/min/1.73 m² -- if we have any hope of preventing kidney failure in the lifetime of people living with IgA nephropathy."
"I think it would be very difficult to justify not giving access to a B-cell-directed therapy in any patient at risk of progression of IgA nephropathy," he added. "These are going to be drugs that you will see used very much more in terms of clinical practice."
ORIGIN
Atacicept is a first-in-class native human TACI-Fc fusion protein that targets two key immunoregulatory cytokines: B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL).
For the studyopens in a new tab or window, a total of 431 adults with biopsy-confirmed IgA nephropathy were randomized to receive weekly subcutaneous atacicept (150 mg) or placebo.
Composite kidney-disease progression -- defined as a sustained decline in eGFR of at least 30% for at least 30 days, a sustained eGFR below 15 mL/min/1.73 m², long-term dialysis, kidney transplantation, or death -- occurred in 5.1% of patients in the atacicept group and 17.8% in the placebo group through week 104. This translated to a 76% lower risk of kidney disease progression with atacicept (HR 0.24, 95% CI 0.12-0.48, P<0.001).
No patients in the atacicept group progressed to dialysis, transplantation, or death, compared with seven patients in the placebo group.
Results were consistent across all prespecified subgroups, including those defined by age, sex, race or ethnic group, geographic region, baseline eGFR, baseline urinary protein-to-creatinine ratio, and baseline SGLT2 inhibitor use.
Adverse events (AEs) occurred in 74.8% of patients in the atacicept group and 78.0% in the placebo group, with serious AEs occurring in 7.0% and 15.4%, respectively. One patient in the placebo group died.
"We are now actively transitioning all those placebo patients onto drug because that's the reason and the driver for why we wanted to look at the data earlier and not expose placebo patients to just standard-of-care therapy," said Barratt.
The findings will be submitted to the FDA to support full approval, he added.
VISIONARY
Sibeprenlimab acts as a humanized IgG2 monoclonal antibody, selectively inhibiting the activity of APRIL to reduce IgA and galactose-deficient IgA1 levels.
Of the 510 patients randomizedopens in a new tab or window, 259 received sibeprenlimab (400 mg every 4 weeks) and 251 received placebo.
A composite kidney end-point event -- defined as the first occurrence of a sustained doubling of the serum creatinine level, a sustained 40% reduction in eGFR, a sustained eGFR below 15 mL/min/1.73 m², or initiation of kidney-replacement therapy -- occurred in one patient (0.4%) in the sibeprenlimab group and 28 patients (11.2%) in the placebo group (adjusted difference -10.8 percentage points). This equated to a 97% risk reduction with sibeprenlimab (HR 0.029, 95% CI 0.004-0.214, P<0.001).
"The safety findings at 24 months were consistent with those reported at the interim analysis," the researchers noted. No deaths occurred, and the incidence of overall AEs, including infections, was similar between the two groups.
Drugmaker Otsuka Pharmaceutical said the findingsopens in a new tab or window were submitted to the FDA for traditional approval.