FDA Approval of Sibeprenlimab Signals New Era in IgA Nephropathy: Jackson Peter Kim, MD

Why It Matters

Sibeprenlimab introduces a novel mechanism that could slow kidney decline in IgAN, offering patients a disease‑modifying option where none existed before.

Key Takeaways

• Accelerated approval based on 50% proteinuria reduction
• First APRIL inhibitor for IgA nephropathy
• Safety profile similar to placebo in trial
• Subcutaneous injection every four weeks
• Long‑term eGFR data pending for full approval

Pulse Analysis

Immunoglobulin A nephropathy has long been managed with renin‑angiotensin blockade and occasional steroids, leaving a therapeutic void for patients at risk of progressive renal failure. The FDA’s accelerated pathway reflects both the unmet need and the promise of sibeprenlimab, an APRIL‑targeting monoclonal antibody that curtails the production of galactose‑deficient IgA, the pathogenic driver of the disease. By intervening earlier in the B‑cell maturation cascade, the drug offers a fundamentally different approach from complement inhibitors or anti‑inflammatory agents, positioning it as a potential disease‑modifying therapy.

The VISIONARY phase 3 trial provided the data foundation for approval, reporting a 51 % placebo‑adjusted reduction in proteinuria after nine months, a surrogate marker strongly linked to long‑term kidney outcomes. Adverse events occurred in 76 % of treated patients versus 85 % on placebo, with serious events under 4 %, underscoring a favorable risk profile. Clinicians are encouraged by the magnitude of proteinuria decline, yet they recognize that sustained eGFR preservation must be demonstrated in the forthcoming 24‑month analysis before the therapy can be fully endorsed as a standard of care.

From a market perspective, sibeprenlimab expands Otsuka’s nephrology portfolio and intensifies competition among emerging biologics targeting IgAN. Its novel mechanism may spur additional research into APRIL and related pathways, potentially unlocking combination strategies with existing complement inhibitors or SGLT2 inhibitors. If the long‑term data confirm renal function benefits, the drug could rapidly become a cornerstone therapy, reshaping treatment algorithms and offering patients a tangible hope of slowing disease progression.

FDA Approval of Sibeprenlimab Signals New Era in IgA Nephropathy: Jackson Peter Kim, MD

By Skylar Jeremias and Jackson Peter Kim, MD · Fact‑checked by Christina Mattina · February 16, 2026

The treatment landscape for immunoglobulin A nephropathy (IgAN) continues to evolve, with the FDA’s recent accelerated approval of sibeprenlimab‑szsi (Voyxact; Otsuka) marking another significant step forward for a disease long defined by limited options and progressive kidney decline. IgAN—also known as Berger disease—is characterized by the buildup of IgA in the kidneys, leading to hematuria, proteinuria, and, over time, loss of kidney function and potential kidney failure. There is no cure, and for years management centered largely on supportive care with renin‑angiotensin system blockade and, in select patients, corticosteroids.

The FDA granted accelerated approval based on interim data from the phase 3 VISIONARY trial, which demonstrated a 50 % reduction in proteinuria at 9 months among patients receiving sibeprenlimab compared with 2 % in the placebo group, yielding a placebo‑adjusted treatment effect of 51 % (P < .0001). All enrolled patients were receiving maximally tolerated standard‑of‑care therapy, and safety findings were favorable, with treatment‑emergent adverse events occurring in 76.3 % of treated patients vs 84.5 % of those receiving placebo. Serious adverse events were reported in 3.9 % and 5.4 %, respectively. The monoclonal antibody, administered as a 400‑mg subcutaneous self‑injection every 4 weeks, works by inhibiting APRIL (A Proliferation‑Inducing Ligand), thereby reducing total IgA and pathogenic galactose‑deficient IgA levels.

In an interview, Jackson Peter Kim, MD, clinical assistant professor in the Division of Nephrology at Stanford Health Care, described his initial reaction as one of optimism. In a field that “was so limited before,” he said, the arrival of a new agent—and recognition from the FDA through the accelerated pathway—was encouraging.

Kim emphasized that sibeprenlimab introduces an entirely new therapeutic branch. Whereas supportive care reduces intraglomerular pressure to lower proteinuria, steroids broadly dampen inflammation and IgA production, and newer agents target complement pathways, this therapy focuses on B‑cell maturation and modulation via APRIL inhibition. “It’s sort of introducing a new branch and an entire new class of medication available for therapy,” he explained.

Proteinuria reduction served as the surrogate end point for accelerated approval, and Kim expressed confidence that the magnitude observed in VISIONARY is clinically meaningful. He pointed to prior influential research demonstrating that higher proteinuria is associated with worse outcomes. “There’s a very meaningful reduction in proteinuria seemingly well tolerated across the safety profile,” he said, adding that he believes the reduction will “translate well into eGFR [estimated glomerular filtration rate] savings over time.”

At the same time, he underscored the distinction clinicians must make when counseling patients. Proteinuria often precedes measurable declines in eGFR, he noted, meaning that short‑term improvements in proteinuria are hoped to signal long‑term preservation of kidney function—but confirmatory data are still needed. A 24‑month analysis of eGFR decline, expected in 2026, will be critical to securing full approval.

Based on interim findings, Kim characterized the overall risk–benefit profile as “profound” and “very beneficial for the right patient,” highlighting the comparable safety profile to placebo alongside substantial proteinuria reduction.

References

1. Shaw ML. FDA approves sibeprenlimab for immunoglobulin A nephropathy. AJMC®. November 26, 2025. Accessed February 16, 2026. https://www.ajmc.com/view/fda-approves-sibeprenlimab-for-immunoglobulin-a-nephropathy

2. FDA approves a new treatment for primary immunoglobulin A nephropathy. FDA News release. November 25, 2025. Accessed November 26, 2025. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-new-treatment-primary-immunoglobulin-nephropathy

3. Otsuka received FDA accelerated approval for Voyxact (sibeprenlimab‑szsi) for the reduction of proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk for disease progression. FDA News release. November 25, 2025. Accessed November 26, 2025. https://otsuka-us.com/news/otsuka-receives-fda-accelerated-approval-voyxactr-sibeprenlimab-szsi-reduction-proteinuria