Otsuka Pharmaceutical has announced positive interim results from its Phase 3 VISIONARY trial, evaluating sibeprenlimab for the treatment of immunoglobulin A nephropathy (IgA nephropathy) in adults. The study met its primary endpoint, demonstrating a statistically significant and clinically meaningful reduction in 24-hour urine protein-to-creatinine ratio (uPCR) after nine months of treatment compared to placebo.
Targeting APRIL in IgA Nephropathy
Sibeprenlimab, developed by Otsuka's subsidiary Visterra, is a monoclonal antibody that targets APRIL (A PRoliferation-Inducing Ligand), a key cytokine involved in the immune pathogenic cascade of IgA nephropathy. By blocking APRIL, sibeprenlimab aims to reduce the production of pathogenic Gd-IgA1 and subsequent immune complex formation, addressing a fundamental driver of nephron loss in IgA nephropathy.
IgA nephropathy, also known as Berger's disease, is a progressive autoimmune kidney disease that can lead to end-stage kidney disease (ESKD). It is characterized by the accumulation of IgA antibodies in the kidneys, causing inflammation and scarring. Current treatments primarily focus on managing symptoms, highlighting the need for therapies that target the underlying disease mechanisms.
VISIONARY Trial Details
The Phase 3 VISIONARY trial (NCT05248646) is a multicenter, randomized, double-blind, placebo-controlled study involving approximately 530 adult patients with IgA nephropathy. Participants were receiving standard-of-care therapy, defined as a maximally tolerated ACE inhibitor or ARB +/- SGLT2 inhibitor. The trial assessed the efficacy and safety of sibeprenlimab 400 mg administered subcutaneously every four weeks compared to placebo. The primary efficacy endpoint was the change in 24-hour uPCR at 9 months compared with baseline.
According to Otsuka, an independent data monitoring committee conducted a pre-specified interim analysis, which confirmed the significant reduction in uPCR with sibeprenlimab treatment. The favorable safety profile of sibeprenlimab was consistent with previously reported data.
Regulatory Pathway and Future Plans
Otsuka plans to discuss these interim results with the FDA to explore a potential regulatory submission for accelerated approval. The ongoing Phase 3 study will continue to evaluate the change in kidney function over 24 months, as measured by estimated glomerular filtration rate (eGFR), with final results expected in early 2026.
"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," said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka Pharmaceutical Development & Commercialization, Inc.
Competitive Landscape
The field of IgA nephropathy treatment is becoming increasingly competitive, with several companies developing therapies targeting different aspects of the disease. Novartis is developing zigakibart, another anti-APRIL antibody, while Vertex Pharma is pursuing povetacicept, a dual antagonist of BAFF and APRIL. Vera Therapeutics is also in late-stage testing with atacicept, which targets APRIL and BLyS. Approved therapies include Calliditas' Tarpeyo (budesonide) and Travere/CSL's Filspari (sparsentan).
Sibeprenlimab's Breakthrough Therapy Designation
Sibeprenlimab received breakthrough therapy designation from the FDA in February, based on positive results from the Phase 2 ENVISION trial. This designation underscores the potential of sibeprenlimab to address a significant unmet need in the treatment of IgA nephropathy.
