Sibeprenlimab Reduces Proteinuria in Phase III IgA Nephropathy Trial

Otsuka Pharmaceutical has announced positive interim results from its Phase III clinical trial for sibeprenlimab. The investigational treatment targets immunoglobulin A nephropathy (IgAN) in adults.

Sibeprenlimab, which has a Breakthrough Therapy designation, is a monoclonal antibody that blocks APRIL (A PRoliferation-Inducing Ligand), a critical step in the immune cascade contributing to IgAN. By neutralizing APRIL, sibeprenlimab reduces the production of galactose-deficient IgA1 (Gd-IgA1), slowing disease progression and reducing proteinuria, a key marker of kidney damage.

IgAN, also known as Berger’s disease, occurs when IgA antibodies build up in the kidneys, leading to inflammation. Many patients with IgAN eventually require dialysis or transplantation. Targeting APRIL could help reduce immune complex formation and kidney inflammation.

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The Phase III VISIONARY trial enrolled 530 adults aged 18 to 65, with varying degrees of kidney function, and most were at risk of progressing to end-stage kidney disease. The trial was conducted across the US, Europe and Asia, ensuring a diverse patient pool. All participants were receiving standard care, including ACE inhibitors or angiotensin II receptor blockers (ARBs).

The primary endpoint of the trial was a reduction in 24-hour urine protein-to-creatinine ratio (uPCR) compared to placebo after nine months of treatment, which indicates improved kidney function. Secondary endpoints, like estimated glomerular filtration rate (eGFR), will be assessed over 24 months to measure long-term effects.

Sibeprenlimab showed a statistically significant reduction in the 24-hour uPCR after nine months. No unexpected safety concerns emerged, and most adverse events were mild to moderate, including injection site reactions, headaches and mild infections.

Otsuka developed sibeprenlimab through its affiliate Visterra, which specializes in precision biologics. The ongoing trial will continue, with final results expected in 2026.

Based on the promising interim data, Otsuka plans to submit the results to the US Food and Drug Administration (FDA) for potential accelerated approval.

Related: The National Kidney Foundation’s Role in Advancing Clinical Trials in Nephrology

Sibeprenlimab’s progress comes amid growing options for IgAN treatment.

Travere Therapeutics’ Filspari (sparsentan) recently received full FDA approval, following accelerated approval, with long-term data confirming its ability to slow kidney function decline.

Calliditas Therapeutics’ Tarpeyo (budesonide) was fully approved early this year after showing a 50 percent reduction in kidney function decline over two years in the NefIgArd trial.

Novartis’ Fabhalta (iptacopan), a complement inhibitor, received accelerated approval after showing a 38 percent reduction in proteinuria in the APPLAUSE-IgAN trial. Fabhalta targets the alternative complement pathway, a key driver in IgAN progression.

In parallel, Vertex Pharmaceuticals is advancing povetacicept, a dual inhibitor of B cell activating factor (BAFF) and APRIL pathways, in its Phase III RAINIER study, expected to launch in 2024.