In a milestone for IgA nephropathy, Otsuka’s Voyxact has shown for the first time in a phase 3 trial that a drug can stabilize patients’ kidney function decline to the normal rate seen in healthy adults.
Results from the phase 3 Visionary trial showed that Voyxact (sibeprenlimab) achieved an annualized estimated glomerular filtration rate (eGFR) slope of a 0.3 mL/min/1.73m² gain over two years, suggesting an improvement in kidney function. The rate matches the normal age-related decline of less than 1 mL/min/1.73m² per year, as laid out in the KDIGO 2025 Clinical Practice Guideline for IgAN.
To be presented at the GlomCon Hawaii 2026 conference, the latest Voyxact result is better than an annualized eGFR slope of negative 4.2 mL/min/1.73m² for placebo. It’s also better than Voyxact’s own performance over 12 months, when it recorded an annualized loss of 3 mL/min/1.73m² at an interim analysis of the Visionary trial.
Voyxact “preserve[s] kidney function, and that’s incredibly important in this disease,” which leads to dialysis and transplant, Otsuka’s chief medical officer, John Kraus, M.D., Ph.D., said in an interview with Fierce Pharma. “Two years of EGFR stability in patients with IgAN is an incredible finding.”
Despite the slight uptick in eGFR slope, Kraus was cautious in calling the outcome “preservation” of kidney function rather than renal “restoration.” The 95% confidence interval for Voyxact’s annualized eGFR slope rate was between negative 0.4 and positive 0.9 mL/min/1.73m².
The annualized eGFR slope, the study’s key secondary endpoint, was calculated with a linear mixed-effects model based on eGFR measurements from Week 4 through Week 104.
At two years, the least-squares mean change from baseline in eGFR was positive 1.3 mL/min/1.73m² for Voyxact, compared with negative 7.9 mL/min/1.73m² with placebo.
The “vast majority of patients” achieved eGFR stabilization over time, and benefits were observed regardless of patients’ background treatment with SGLT2 inhibitors or baseline proteinuria levels, according to Kraus. The team is conducting additional analyses among a cohort of patients with severe disease with very low eGFR at baseline, plus a biomarker study to dig deeper into the physiology of the treatment effect, he said. Some additional analyses are slated for the American Society of Nephrology annual meeting in October.
In terms of tolerability, Kraus pointed to a safety profile “that’s very similar to placebo.” The rate of treatment-related adverse events was about 35% for Voyxact and 33% for placebo.
Voyxact is the first drug that targets A proliferation-inducing ligand (APRIL), a signaling protein that helps certain B cells survive and make antibodies. In IgAN, it works by lowering the levels of harmful IgA antibodies. As an immune modulator, Voyxact showed a lower rate of infections and infestations, at 1.9%, compared with 4% in placebo.
The latest data could offer a boost in confidence for Voyxact and the anti-APRIL class after an interim analysis of Visionary disappointed industry watchers last year. Besides the 3 mL/min/1.73m² eGFR slope loss at Week 48 undershooting expectations, the detection of anti-drug antibodies also raised concerns over long-term efficacy at the time.
Otsuka doesn’t have a two-year update on anti-drug antibodies. But Kraus argued that, while 34% of patients developed them, only 8% had neutralizing antibodies.
“It’s not unusual to have anti-drug antibodies. The key thing is, do they impact efficacy in the patient population,” Kraus said. “Again, what we see in that two-year data, particularly if you look at that figure and the lower bound of that error bar, we don’t seem to see any evidence of loss of efficacy over time.”
The new eGFR data also put Voyxact in a better position amid a wave of APRIL/BAFF dual inhibitors, led by Vera Therapeutics’ newly FDA-approved Trutakna (atacicept). In a phase 2b trial, Trutakna showed an annualized eGFR slope of negative 0.6 mL/min/1.73m² over 96 weeks. Vera expects to read out its own phase 3 eGFR slope data in the third quarter.
With the kidney function stabilization readout, “it tells me that APRIL is sufficient to have a profound effect on preservation of renal function,” Kraus said.
Otsuka is filing the latest data with the FDA to convert Voyxact’s accelerated approval to a full nod. In that submission, the company also plans to introduce an autoinjector version in addition to the existing prefilled syringe, which patients inject themselves.
Following its initial go-ahead in November 2025, Voyxact has been off to a strong start. For the first half of 2026, Otsuka reported Voyxact sales of 17.1 billion Japanese yen ($110 million). Citing stronger-than-expected launch uptake, Otsuka just more than doubled its full-year forecast for the drug from 25 billion yen to 60 billion yen, while moving up its 100 billion-yen sales target from 2028 to 2027.