Sibeprenlimab Meaningfully Reduces uPCR in Adults With IgA Nephropathy

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Sibeprenlimab produced a significant and clinically meaningful reduction in 24-hour urine protein-to-creatine ratio (uPCR) in adults with immunoglobulin A (IgA) nephropathy, according to an interim analysis of the phase 3 VISIONARY (NCT05248646) study, which has now met its primary endpoint.¹

“The positive interim data from this trial suggest that by targeting APRIL, we could provide a new therapeutic strategy for people living with this progressive kidney disease,” John Kraus, MD, PhD, executive vice president and chief medical officer, Otsuka Pharmaceutical Development & Commercialization, said in a statement.¹ “We look forward to the completion of this study and reviewing the full results at a future timepoint. We are deeply appreciative to the patients with IgA nephropathy who participated in this trial, their caregivers, and investigators, all of whom continue to contribute greatly to this research.”

IgA nephropathy, also known as Berger’s disease, is a progressive, autoimmune, chronic kidney disease that can lead to end-stage kidney disease (ESKD) in most patients’ lifetimes under standard care.Sibeprenlimab is an investigational, anti-APRIL monoclonal antibody (A PRoliferation-Inducing Ligand) designed to disrupt a key step in the immune pathologic cascade of IgA nephropathy by limiting Gd-IgA1 production and immune complex formation.

The multicenter, randomized, double-blind, placebo-controlled VISIONARY study assessed sibeprenlimab 400 mg subcutaneously every 4 weeks against placebo in around 530 adult participants with IgA nephropathy who were previously receiving standard of care maximally tolerated ACE inhibitors or ARB +/- SGLT2 inhibitors over 9 months of treatment.

The VISIONARY study is ongoing with an expected completion date in early 2026 and will continue to evaluate the change in kidney function over 24 months, as measured by estimated glomerular filtration rate (eGFR). Otsuka will also conduct further analyses to assess the efficacy of sibeprenlimab. These interim analysis data may support regulatory submission for accelerated approval, pending discussion with the FDA.

“We are encouraged by sibeprenlimab’s continuing progress and its potential to provide a needed and possibly disease-modifying treatment option to IgA nephropathy patients,” Brian Pereira, MD, CEO, Visterra, Otsuka’s US affiliate which designed and engineered sibeprenlimab, added.¹

Further data on sibeprenlimab, from the phase 2 ENVISION trial (NCT04287985) will be presented at the upcoming American Society of Nephrology (ASN) Kidney Week Meeting, set for October 23-26 in San Diego, California.²

ENVISION was a 12-month, global, randomized, controlled trial that evaluated monthly sibeprenlimab (2, 4, or 8 mg/kg IV) in adults with IgA nephropathy. Study partiicpants experienced sustained, dose-dependent, reversible reductions in IgG/IgA- and IgM/IgA-CICs compared with those receiving placebo. At month 12, investigators found that the median IgG/IgA-CIC was 81.65%, 72.34%, and 66.67% of baseline in participants receiving sibeprenlimab 2, 4, and 8 mg/kg, respectively, while the placebo group had a median of 102.26%, and median IgM/IgA-CIC was 37.05%, 30.37%, and 30.11% of baseline for IgM/IgA-CIC, respectively, while the placebo group had a median of 95.54%.²

REFERENCES
1. Otsuka Announces Positive Interim Results from the Phase 3 Trial of Sibeprenlimab for the Treatment of Immunoglobulin A Nephropathy in Adults. News release. Otsuka. October 22, 2024. https://www.businesswire.com/news/home/20241022946593/en/Otsuka-Announces-Positive-Interim-Results-from-the-Phase-3-Trial-of-Sibeprenlimab-for-the-Treatment-of-Immunoglobulin-A-Nephropathy-in-Adults

2. Barrat J, Mathur M, Liew A, et al. The Anti-APRIL Antibody Sibeprenlimab Reduces Circulating Immune Complexes in Patients with IgAN: The Phase 2 ENVISION Randomized Controlled Trial. Presented at: ASN Kidney Week 2024, held October 24-26 in San Diego, California. Abstract FR-OR59