Monthly therapy preserves kidney function in IgAN trial, final data show
Phase 3 study also shows Voyxact reduced risk of kidney failure events
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The approved therapy Voyxact can prevent kidney function worsening and kidney failure in adults with immunoglobulin A nephropathy, according to final results from a clinical trial. (Photo from iStock)
The approved, monthly therapy Voyxact (sibeprenlimab-szsi) can prevent kidney function worsening and kidney failure in adults with immunoglobulin A nephropathy (IgAN), according to final two-year results from a global, late-stage clinical trial.
“VOYXACT delivered durable stabilization of kidney function and substantially reduced the risk of kidney failure events, with a safety profile comparable to placebo over two years,” John Kraus, M.D., Ph.D., executive vice president and chief medical officer at Otsuka, the therapy’s maker, said in a company press release. He also noted that the magnitude and durability of the therapy’s effect are “rarely seen in kidney outcome trials.”
Full findings from the Phase 3 VISIONARY trial (NCT05248646), which was sponsored by Otsuka, were published in The New England Journal of Medicine in a study titled “Sibeprenlimab in IgA Nephropathy — Final Phase 3 Trial Analysis.” They were also presented at the American Society of Nephrology Kidney Week 2026, held Oct. 21-25 in Denver.
These data “redefine what may be possible for people living with IgA nephropathy,” Kraus said.
Application for full approval submitted
Voyxact is conditionally approved in the U.S. to treat adults with IgAN who are at risk of disease progression. Conditional, or accelerated, approval allows an experimental therapy to be marketed based on preliminary evidence of its efficacy. Full approval is dependent on additional clinical trial data confirming its therapeutic benefits.
The trial’s final kidney function results have now been included in an application submitted by Otsuka to the U.S. Food and Drug Administration (FDA) seeking a transition to full approval.
The therapy will also be tested in pediatric IgAN patients, ages 2 to 17 years, as an add-on to standard therapy in a Phase 3 trial (NCT07770815). Study locations were not yet disclosed, but patient enrollment is expected to start soon.
IgAN is marked by the buildup of a specific type of antibody, called IgA, in the kidneys, which triggers inflammation that damages kidney tissue. An inflammatory signaling molecule called APRIL is thought to play a key role in driving inflammatory damage in IgAN.
Voyxact, given via under-the-skin injection once a month, is designed to reduce disease activity by blocking APRIL. The therapy’s accelerated approval was based on preliminary data from the Phase 3 VISIONARY trial, which tested the therapy against a placebo in more than 500 adults with IgAN.
Specifically, the FDA allowed Voyxact to be brought to market based on trial data showing that the therapy helped reduce proteinuria (high levels of protein in the urine), which is a sign of kidney damage, after nine months.
A reduction in proteinuria therefore suggests that Voyxact may benefit patients. But showing that a therapy can reduce urine protein levels doesn’t definitively prove that the treatment will preserve kidney function over time.
Measure of kidney function improves
The full VISIONARY results showed how Voyxact affected a measure of kidney function called the estimated glomerular filtration rate (eGFR), which measures how efficiently the kidneys can filter blood. eGFR is expressed in units called ml per minute per 1.73 square meter (m2).
In untreated IgAN, eGFR tends to worsen over time as the kidneys accumulate damage. Over the course of two years in the VISIONARY study, that’s exactly what happened for participants given the placebo: eGFR worsened at a rate of 4.2 ml per minute per 1.73 m2 per year.
For clinicians, the consistency and magnitude of these results provide compelling evidence that [Voyxact] delivers a significant treatment effect.
But in those given Voyxact, average eGFR did not worsen over the course of the two-year study. In fact, the average eGFR actually improved, at a rate of 0.3 ml per minute per 1.73 m2 each year. This difference between the placebo and Voyxact groups was statistically significant.
“For patients with IgA nephropathy, preserving kidney function and preventing kidney failure are the outcomes that matter most,” said Dana Rizk, MD, VISIONARY study site principal investigator at the University of Alabama at Birmingham and co-chair of the trial’s steering committee.
Voyxact was also associated with a significantly lower risk of experiencing a substantial drop in kidney function or progressing to kidney failure. Specifically, over the course of the study, 28 people on the placebo (11.2%) and only one treated with Voyxact (0.4%) met such composite outcome.
“In the largest Phase 3 IgA nephropathy dataset reported to date, VISIONARY demonstrated sustained kidney function stabilization over two years. … The trial also showed a 97.1% reduction in the risk of kidney failure events,” Rizk said. “For clinicians, the consistency and magnitude of these results provide compelling evidence that [Voyxact] delivers a significant treatment effect.”
Full safety data were consistent with earlier data from the VISIONARY study, with the most commonly reported adverse events being infections and infestations. Rates of serious and severe adverse events, serious infections, and treatment discontinuations were lower in the Voyxact group relative to the placebo group.
“These findings suggest that selective APRIL [suppression] has the potential to change the long-term trajectory of IgA nephropathy and redefine what may be possible for patients living with this progressive disease,” Rizk added.
