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Key takeaways
Promising interim results support APRIL inhibition as a viable IgAN strategy: Sibeprenlimab achieved a 51.2% reduction in proteinuria at 9 months, marking a strong signal of efficacy for this investigational biologic.
Strong operational execution in largest IgAN trial to date: The Phase III VISIONARY trial enrolled 510 diverse patients across multiple sites, highlighting scalable study design and patient recruitment strategies in rare kidney diseases.
Consistent safety profile helps de-risk ongoing development: Favorable safety data in both Phase II and Phase III support continued long-term evaluation, critical for programs targeting chronic, progressive conditions.
Otsuka has shared positive data from its Phase III VISIONARY clinical trial (NCT05248646) of sibeprenlimab in adults with immunoglobulin A nephropathy (IgAN). The investigational monoclonal antibody demonstrated a 51.2% reduction in proteinuria (as measured by 24-hour uPCR [urine protein-to-creatinine ratio]) at nine months of treatment when compared to placebo in patients with IgAN. Detailed results from the study were presented at the European Renal Association (ERA) Congress in Vienna, Austria.1
Safety profile of sibeprenlimab remains favorable and consistent
In addition to the meaningful reduction in proteinuria, sibeprenlimab demonstrated a favorable and consistent safety profile. Of patients treated with sibeprenlimab, 76.3% experienced treatment emergent adverse events (TEAEs) versus 84.5% in the placebo group. Those who experienced serious TEAE were 3.9% treated with sibeprenlimab compared to 5.4% treated with placebo.
In a press release, John Kraus, MD, PhD, executive vice president and chief medical officer, Otsuka, said: “We are confident about the potential of sibeprenlimab and are grateful to the patients who are helping to further the science by participating in these important trials. Proteinuria control is an important independent predictor for long-term prognosis, and this interim data reinforces our belief that selectively targeting APRIL has the potential to be an effective and safe approach for this progressive and irreversible kidney disease.”
VISIONARY trial design: Largest IgAN study conducted to date
According to Otsuka, the multicenter, randomized, double-blind, placebo-controlled VISIONARY trial is the largest IgAN study to date. Approximately 510 adults with IgAN who were receiving standard-of-care therapy (defined as maximally tolerated ACE inhibitor or ARB +/- SGLT2 inhibitor) participated.
Patients received a subcutaneous 400 mg dose of sibeprenlimab every four weeks, with outcomes being compared to a placebo arm. The primary endpoint is change in 24-hour uPCR at 9 months compared with baseline. There is also a secondary endpoint of annualized slope of estimated glomerular filtration rate (eGFR) over 24 months.
Otsuka anticipates the study to conclude in early 2026 as it continues to evaluate change in kidney function over 24 months as measured by eGFR. The company will explore data even further to determine the full potential of sibeprenlimab in treating IgAN.
In the press release, Dana Rizk, MD, professor of medicine in the division of nephrology at the University of Alabama at Birmingham, added: “The VISIONARY Phase III interim analysis shows a robust proteinuria reduction of 51.2% in the group treated with sibeprenlimab relative to placebo. These results affirm our belief in the efficacy of sibeprenlimab in the largest Phase III IgAN trial to date. The study enrolled a diverse patient population reflective of the disease epidemiology. The safety data emerging from VISIONARY is reassuring and adds to our existing knowledge about sibeprenlimab’s safety profile from prior programs. This is very exciting news for patients and adds a therapeutic option with a novel mechanism of action potentially targeting the immunologic pathogenesis of IgAN.”
Phase II study reinforces efficacy signal ahead of final readout
In November 2023, Otsuka announced positive data from a Phase II study of sibeprenlimab in IgAN. Results showed that 12 months of treatment with sibeprenlimab led to significant reductions in proteinuria compared to placebo.2
The Phase II study randomized 155 adult participants with biopsy-confirmed IgAN to receive monthly intravenous injections of sibeprenlimab at doses of 2, 4, or 8 mg/kg, or placebo for 12 months. The primary outcome measure was change from baseline in 24-hour uPCR at 12 months. Secondary outcomes included safety and change in eGFR.
In a press release from the time, Kraus said: “We are excited by these results, which bring us one step closer to addressing the critical unmet treatment needs of patients with this complex, life-threatening condition. We look forward to continuing to evaluate the potential of sibeprenlimab in the ongoing Phase III trial program.”
References
1. Otsuka Sibeprenlimab Phase 3 Data Show a Statistically Significant and Clinically Meaningful Proteinuria Reduction for the Treatment of Immunoglobulin A Nephropathy (IgAN). News release. Otsuka. June 6, 2025. Accessed June 6, 2025. https://www.businesswire.com/news/home/20250606873555/en/Otsuka-Sibeprenlimab-Phase-3-Data-Show-a-Statistically-Significant-and-Clinically-Meaningful-Proteinuria-Reduction-for-the-Treatment-of-Immunoglobulin-A-Nephropathy-IgAN
2. New England Journal of Medicine Publishes Complete Results of Positive Phase 2 Trial of Sibeprenlimab in Treatment of Immunoglobulin A Nephropathy (IgAN). News release. Otsuka. November 2, 2023. Accessed June 6, 2025. https://www.businesswire.com/news/home/20231102845310/en/New-England-Journal-of-Medicine-Publishes-Complete-Results-of-Positive-Phase-2-Trial-of-Sibeprenlimab-in-Treatment-of-Immunoglobulin-A-Nephropathy-IgAN