FDA Approves Sibeprenlimab for Patients with IgAN

The FDA approved sibeprenlimab (Voyxact; Otsuka Pharmaceutical Co., Ltd, Visterra, Inc.), a monoclonal antibody targeting the cytokine A Proliferation-Inducing Ligand (APRIL), as a treatment for patients with immunoglobulin A nephropathy (IgAN).¹

The manufacturers previously submitted a biologics license application (BLA) and a breakthrough therapy designation, the latter of which was granted by the FDA. The manufacturers also requested a priority review with a Prescription Drug User Fee Act (PDUFA) target date of November 28, 2025.^2-4

How Will Sibeprenlimab Help Patients with IgAN?

IgAN, also known as Berger disease, is a progressive glomerular disease characterized by the accumulation of the immune protein IgA in the kidneys. As the disease progresses, it can cause proteinuria—excessive protein in the urine—and scarring and inflammation that impedes kidney function and ultimately causes end-stage kidney disease and kidney failure. There is no cure; treatments focus on slowing progression. The cause is not known.⁵

Sibeprenlimab represents a change in this current standard. Because it selectively binds to and inhibits APRIL, it can reduce IgA buildup, thereby preventing inflammation and kidney damage. This makes it the first medication for patients with IgAN that does more than merely slow progression: it modifies the disease itself and targets its long-term consequences, underscoring the unmet need for patients with IgAN.^3,6,7

How Does the Clinical Evidence Support Sibeprenlimab as a Treatment for IgAN?

The BLA submission was supported by phase 2 and phase 3 clinical trials. Patients enrolled in the phase 2 ENVISION trial (NCT04287985) demonstrated a significant reduction in proteinuria compared with placebo, which led to the FDA granting breakthrough therapy designation in 2024.^8,9

The phase 3 VISIONARY trial (NCT05248646) enrolled 530 adult patients with IgAN on standard-of-care therapy (angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers with or without a sodium-glucose cotransporter 2 inhibitor) and evaluated 400 mg of sibeprenlimab, administered subcutaneously every 4 weeks, compared with placebo. The primary end point was the change in 24-hour urine protein-to-creatinine ratio (uPCR) at 9 months; the secondary endpoint is the annualized slope of eGFR over ~24 months.¹⁰

An interim analysis of the VISIONARY study showed patients on sibeprenlimab demonstrated substantial reductions in proteinuria compared with placebo. At approximately 9 months, treatment produced a 51.2% decrease in uPCR versus placebo (P < .0001). By around 12 months, the treatment arm achieved an approximate 56.6% reduction in uPCR compared with 5.1% in the placebo group, resulting in a placebo-adjusted decrease of about 54.3% (95% CI, 46.4%–60.9%).¹¹

Furthermore, sibeprenlimab also demonstrated a favorable safety profile, with treatment-emergent adverse events (AEs) reported in roughly 74.1% of sibeprenlimab-treated patients compared with 82.1% of those receiving placebo, most of which were mild to moderate in severity. Reductions in proteinuria are a validated surrogate end point in IgAN trials and are associated with a delay in progression to kidney failure.^9,11

What Does the Approval of Sibeprenlimab Mean for Patients and Pharmacists?

The approval of sibeprenlimab represents a meaningful advance in the management of IgAN. As the first therapy to directly target APRIL and modify the underlying disease process rather than simply slow progression, sibeprenlimab introduces new considerations for monitoring, adherence, and long-term outcome expectations. Pharmacists will play a key role in educating patients on the mechanism of action, administration schedule, and the importance of maintaining standard-of-care therapies alongside treatment.

Pharmacists will also be central to identifying and managing mild-to-moderate AEs, ensuring continuity of care, and helping providers interpret changes in proteinuria and kidney function as evidence evolves. Overall, sibeprenlimab’s introduction adds a transformative option to the therapeutic landscape, reinforcing the pharmacist’s role as an essential partner in chronic kidney disease management.

REFERENCES

1. US Food and Drug Administration. FDA approves new treatment for primary immunoglobulin A nephropathy (IgAN). US Food and Drug Administration. November 25, 2025. Accessed November 26, 2025. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-new-treatment-primary-immunoglobulin-nephropathy

2. Myshko D. FDA Grants Priority Review to Sibeprenlimab for the Kidney Disease IgAN. Managed Healthcare Executive. May 27, 2025. Accessed November 18, 2025. https://www.managedhealthcareexecutive.com/view/fda-grants-priority-review-to-sibeprenlimab-for-the-kidney-disease-igan

3. Otsuka Pharmaceutical Development & Commercialization, Inc. Otsuka Announces FDA Acceptance and Priority Review of Biologics License Application (BLA) for Sibeprenlimab in the Treatment of Immunoglobulin A Nephropathy (IgAN). News Release; May 27 2025. Accessed November 20, 2025. https://www.otsuka-us.com/news/otsuka-announces-fda-acceptance-and-priority-review-biologics-license-application-bla

4. Otsuka Pharmaceutical Development & Commercialization, Inc. Otsuka Files Biologics License Application (BLA) for Sibeprenlimab for the Treatment of Immunoglobulin A Nephropathy (IgAN). News Release; March 31, 2025. Accessed November 19, 2025. https://www.otsuka-us.com/news/otsuka-files-biologics-license-application-bla-sibeprenlimab-treatment-immunoglobulin

5. National Kidney Foundation. IgA Nephropathy (IgAN). National Kidney Foundation. Updated April 17, 2024. Accessed November 25, 2025. https://www.kidney.org/kidney-topics/iga-nephropathy

6. Drug-Dev.com. Sibeprenlimab’s Priority Review Highlights Potential to Differentiate in IgAN Space. May 29, 2025. Accessed November 18, 2025. https://drug-dev.com/sibeprenlimabs-priority-review-highlights-potential-to-differentiate-in-igan-space/

7. Pharmaceutical-Technology. FDA to review Otsuka’s sibeprenlimab application for IgAN. May 27, 2025. Accessed November 18, 2025. https://www.pharmaceutical-technology.com/news/fda-otsuka-igan/

8. Otsuka Pharmaceutical Development & Commercialization, Inc.; Otsuka Pharmaceutical Co., Ltd.; and Visterra, Inc. Sibeprenlimab Receives U.S. FDA Breakthrough Therapy Designation for the Treatment of Immunoglobulin A Nephropathy. Otsuka US News, February 16, 2024. Accessed November 25, 2025. https://www.otsuka-us.com/news/sibeprenlimab-receives-us-fda-breakthrough-therapy-designation-treatment-immunoglobulin

9. Otsuka Pharmaceutical Co., Ltd. Sibeprenlimab Phase 3 Data Presented at American Society of Nephrology Kidney Week 2025 Showed Proteinuria Reduction through 12 Months for the Treatment of IgA Nephropathy (IgAN). News Release; November 10, 2025. https://www.otsuka.co.jp/en/company/newsreleases/2025/20251110_1.html

10. Visterra, Inc. Safety and Efficacy Study of VIS649 for IgA Nephropathy. ClinicalTrials.gov. NCT04287985. https://clinicaltrials.gov/study/NCT04287985. Accessed November 24, 2025.

11. Visterra, Inc.; Otsuka Pharmaceutical Development & Commercialization, Inc. A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Sibeprenlimab Administered Subcutaneously in Subjects With Immunoglobulin A Nephropathy. ClinicalTrials.gov. NCT05248646. https://clinicaltrials.gov/study/NCT05248646. Accessed on November 24, 2025.