Voyxact (sibeprenlimab-szsi) / Otsuka - LARVOL DELTA

Otsuka's kidney disease mAb wins FDA accelerated approval (Firstwordpharma Press Release) - "Following a priority review, the FDA on Friday granted accelerated approval to Otsuka Pharmaceutical's Voyxact (sibeprenlimab-szsi) to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk for disease progression....The mAb's approval was informed by findings from the 510-patient Phase III VISIONARY trial, which compared Voyxact to placebo in patients with IgAN who were receiving standard-of-care therapy."

Accelerated approval • FDA approval • IgA Nephropathy

Sibeprenlimab for the Treatment of IgAN: VISIONARY Phase 3 Interim and Prespecified Subgroup Analyses (KIDNEY WEEK 2025) - P3 | "Conclusion Sibeprenlimab reduced proteinuria and biomarkers and led to higher rates of hematuric/proteinuric remission up to 12 mos, with favorable safety; benefits were consistent across subgroups. VISIONARY is ongoing, evaluating sibeprenlimab’s safety and efficacy (eGFR) over 24 mos."

Late-breaking abstract • P3 data • P3 data: top line • Glomerulonephritis • IgA Nephropathy

Sibeprenlimab in IgA Nephropathy - Interim Analysis of a Phase 3 Trial. (PubMed, N Engl J Med) - P3 | "Sibeprenlimab resulted in a significant reduction in proteinuria as compared with placebo in patients with IgA nephropathy. (Funded by Otsuka Pharmaceutical Development and Commercialization. VISIONARY ClinicalTrials.gov number, NCT05248646.)."

Journal • P3 data • P3 data: top line • Glomerulonephritis • IgA Nephropathy • Renal Disease

Preclinical Characterization of IBI3034, an TACI and BCMA Chimeric Fc Fusion Protein, that Potently Modulates B Lymphocytes and Serum Immunoglobulin for the Treatment of B cell Related Autoimmune Disease (ACR Convergence 2025) - "Therapeutic agents targeting these cytokines, including the anti-BAFF antibody Belimumab, anti-APRIL antibody Sibeprenlimab, and the BAFF/APRIL dual inhibitor Telitacicept, have demonstrated significant clinic efficacy, particularly in SLE and IgAN. IBI3034, a novel TACI/BCMA chimeric Fc fusion protein, exhibits potent and prolonged effects on B-cell and plasma cell depletion and immunoglobulin suppression through balanced dual inhibition of BAFF and APRIL. This innovative therapeutic approach holds promise for providing deeper clinical benefits and more convenient dosing intervals for patients with B-cell-mediated autoimmune diseases."

Preclinical • Glomerulonephritis • IgA Nephropathy • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Renal Disease • Rheumatoid Arthritis • Rheumatology • Systemic Lupus Erythematosus

A Trial to Evaluate the Efficacy and Safety of Sibeprenlimab Administered Subcutaneously in Participants With Sjögren's (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Sjogren's Syndrome

Safety and Tolerability, and PK of Sibeprenlimab in Chinese Healthy Subject (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Otsuka Beijing Research Institute

New P1 trial

Efficacy and safety of agents for IgA nephropathy: a network meta-analysis of randomized controlled trials. (PubMed, Front Med (Lausanne)) - "Clinical remission (26 RCTs included in the analysis): The CR for tonsillectomy combined with steroids pulse therapy (TSP) (RR = 8.23, 95% CI 4.11-16.45), anti-APRIL monoclonal antibody sibeprenlimab (RR = 10.00, 1.34-74.48), and steroids combined with renin-angiotensin system inhibitors (STE + RASI) (RR = 5.03, 2.61-9.68) were significantly superior to placebo. Proteinuria control (36 studies assessing 24-h UPE): The BLyS/APRIL dual-target inhibitor telitacicept (SMD = -5.21, -7.55 to -2.87) and STE + RASI (SMD = -1.98, -3.15 to -0.82) significantly reduced 24-h UPE, outperforming the mycophenolate mofetil combined with steroids regimen (SMD = -0.97, -2.74 to 0.80)...Safety (36 studies reporting adverse events): The complement inhibitor iptacopan (88.4%) and sodium-glucose co-transporter 2 inhibitors (SGLT2i) (85.4%) had the lowest incidence of adverse events, significantly better than immunosuppressive regimens...Telitacicept, sparsentan, and TSP can be considered as..."

Journal • Retrospective data • Review • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Nephrology • Renal Disease

Online Education Improved Nephrologists' Knowledge of The Immunopathogenesis of Immunoglobulin A Nephropathy and Rationale for Novel Therapies (ERA 2025) - "Nephrologists significantly improved their knowledge of the immunopathogenesis of IgAN (58% correct responses at baseline rising to 74% post-activity; P <.001), and the MOA of the emerging IgAN therapy iptacopan acting via the alternative complement pathways (73% vs 85% post-activity; P <.01). There was a numerical improvement in knowledge of the MOA of the APRIL (proliferation-inducing ligand) inhibitor sibeprenlimab acting via reduction of circulating levels of galactose-deficient IgA1 (Gd-IgA1) and associated immune complexes (48% vs 56% post- activity; P =.070)... This online activity significantly improved nephrologists' knowledge of the immunopathogenesis of IgAN and the rationale and MOA of some emerging therapies for IgAN. Given the rapidly evolving treatment landscape for IgAN, nephrologists would benefit from additional education to improve their knowledge of emerging therapies and translate this knowledge into clinical practice and improved patient..."

Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Nephrology • Renal Disease

Sibeprenlimab for Patients With IgA Nephropathy: Results From a Prespecified Interim Analysis of the Phase 3 VISIONARY Study (ERA 2025) - P3 | "In this prespecified interim analysis of VISIONARY (the largest phase 3 IgAN trial to date), the primary study endpoint was met. The targeted APRIL inhibitor sibeprenlimab demonstrated a significant and robust reduction in proteinuria after 9 months of treatment compared with placebo, along with a favorable safety profile. As proteinuria is an important independent predictor for long-term prognosis in IgAN, reductions of this magnitude are likely to result in a clinically meaningful stabilization of eGFR decline, which will be formally assessed at a later timepoint."

Clinical • Late-breaking abstract • P3 data • P3 data: top line • Glomerulonephritis • IgA Nephropathy • Infectious Disease • Lupus Nephritis • Renal Disease

Clinical Practice Gaps in the Diagnosis and Management of Immunoglobulin A Nephropathy (ERA 2025) - " •395 nephrologists completed all questions within the data collection timeframe •76% of nephrologists saw between 1 and 10 patients per month with IgAN •38% failed to recognise that the RaDaR study showed that IgAN is progressive even in patients thought to be at low risk (proteinuria < 1 g/d) •17% could not correctly identify that the most common clincial presentation of IgAN is asymptomatic microscopic hematuria and proteinuria •44% did not recognise the presence of tubular atrophy (T), a finding of the MEST-C score, is a consistent, independent predictor of worse outcomes in patients with IgAN •34% did not identify the correct order of the multihit hypothesis of the pathophysiology of IgAN •Only 21% knew that production of Gd-IgA1 is a mechanism via which the cytokines a proliferation inducing ligand (APRIL) and B-cell activating factor (BAFF) drive IgAN pathogenesis •66% did not recognise that, according to 2021 KDIGO guidelines, considering enrollment in a..."

Clinical • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Renal Disease

Patient baseline characteristics in the ongoing phase 3 VISIONARY Trial: A randomized, placebo-controlled study of sibeprenlimab for immunoglobulin A nephropathy (UKKW 2025) - P3 | "N Engl J Med. 2024;390(1):20–31."

Clinical • P3 data • Glomerulonephritis • IgA Nephropathy • Renal Disease

The anti-APRIL antibody sibeprenlimab reduced circulating immune complexes in patients with IgA nephropathy in the phase 2 ENVISION randomized controlled trial (UKKW 2025) - No abstract available

Clinical • P2 data • Glomerulonephritis • IgA Nephropathy • Renal Disease

Otsuka Sibeprenlimab Phase 3 Data Show a Statistically Significant and Clinically Meaningful Proteinuria Reduction for the Treatment of Immunoglobulin A Nephropathy (IgAN) (Yahoo Finance) - P3 | N=530 | VISIONARY (NCT05248646) | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | "Patients treated with sibeprenlimab achieved a 51.2% (P<0.0001) reduction in proteinuria (as measured by 24-hour uPCR [urine protein-to-creatinine ratio]) at nine months of treatment when compared to placebo. The data were presented during a late-breaking clinical trials session at the European Renal Association (ERA) Congress in Vienna, Austria. The study, the largest Phase 3 IgAN trial conducted to date, also showed the safety profile of sibeprenlimab was favorable and consistent with previously reported data. Specifically, 76.3% of patients treated with sibeprenlimab experienced any Treatment Emergent Adverse Event (TEAE) versus 84.5% in the placebo group. Patients who experienced a serious TEAE were 3.9% treated with sibeprenlimab compared to 5.4% treated with placebo."

P3 data • IgA Nephropathy

Otsuka Announces FDA Acceptance and Priority Review of Biologics License Application (BLA) for Sibeprenlimab in the Treatment of Immunoglobulin A Nephropathy (IgAN) (Otsuka Press Release) - "Otsuka Pharmaceutical, Co. Ltd...announce the U.S. Food and Drug Administration (FDA) has accepted for review the Biologics License Application (BLA) for sibeprenlimab, an investigational monoclonal antibody that selectively inhibits the activity of APRIL (A PRoliferation-Inducing Ligand) in adults with immunoglobulin A nephropathy (IgAN). APRIL plays a key role in the pathogenesis of IgAN as explained by the 4-hit process, in which pathogenic galactose-deficient IgA (Gd-IgA1) is produced, leading to the synthesis of autoantibodies against Gd-IgA1, immune complex formation, and deposition in the glomerular mesangium...The BLA is supported by the Phase 3 VISIONARY clinical trial (NCT05248646), which met its primary endpoint at the prespecified interim analysis, and results from the Phase 2 ENVISION clinical trial (NCT04287985)....The BLA has been granted priority review and a Prescription Drug User Fee Act (PDUFA) target action date of November 28, 2025."

FDA filing • PDUFA • Priority review • IgA Nephropathy • Immunology

Safety Reporting for Auxiliary Medicinal Products in the Sibeprenlimab Phase-III Study According to the New European Union (536/2014) CT Regulation. (PubMed, Curr Drug Saf) - "From the gap analysis and impact assessment of EU CTR, appropriate changes were made to the existing PV processes, study-specific documents, and the safety database to ensure compliance with the EU CTR."

Journal • P3 data

Otsuka Files Biologics License Application (BLA) for Sibeprenlimab in the Treatment of Immunoglobulin A Nephropathy (Businesswire) - "Otsuka Pharmaceutical Development & Commercialization...announce the filing of a Biologics License Application (BLA) with the U.S. Food and Drug Administration (FDA) for sibeprenlimab, an investigational monoclonal antibody that selectively inhibits the activity of APRIL (A PRoliferation-Inducing Ligand) in adults with immunoglobulin A nephropathy (IgAN)....Sibeprenlimab is a single-dose prefilled syringe for subcutaneous injection every four weeks intended for self-administration or administration by caregiver....The BLA submission, Otsuka’s first, is supported by results from the Phase 2 ENVISION clinical trial (NCT04287985) and the Phase 3 VISIONARY clinical trial (NCT05248646), which met its primary endpoint by demonstrating that sibeprenlimab produced a statistically significant and clinically meaningful reduction in 24-hour uPCR (urine protein-to-creatine ratio) compared to placebo after nine months of treatment."

FDA filing • IgA Nephropathy

A Trial to Evaluate the Efficacy and Safety of Sibeprenlimab Administered Subcutaneously in Participants With Sjögren's (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

New P2 trial • Sjogren's Syndrome

Title: Patient Baseline Characteristics in the Ongoing Phase 3 VISIONARY Trial: A Randomized, Placebo-Controlled Study of Sibeprenlimab for Immunoglobulin A Nephropathy (NKF-SCM 2025) - P3 | "Demographic/baseline characteristics including kidney biopsy data were summarized using descriptive statistics.Results Demographic and baseline characteristics, and kidney biopsy data from 510 randomized pts are reported in the Table .Conclusion VISIONARY enrolled a large, diverse population of IgAN pts at high risk for disease progression to evaluate efficacy and safety of sibeprenlimab SC. Clinical results will be reported at a future date."

Clinical • P3 data • Glomerulonephritis • IgA Nephropathy • Renal Disease

A novel agent targeting APRIL: A new hope for elderly patients of IgA nephropathy. (PubMed, Aging Med (Milton)) - "Sibeprenlimab is a humanized IgG2 monoclonal antibody that binds to and neutralizes the activity of APRIL. It should usher in a new era in the treatment of IgAN, especially in elderly patients."

Journal • Glomerulonephritis • IgA Nephropathy • Renal Disease

PATIENT BASELINE CHARACTERISTICS IN THE ONGOING PHASE 3 VISIONARY TRIAL: A RANDOMIZED, PLACEBO-CONTROLLED STUDY OF SIBEPRENLIMAB FOR IMMUNOGLOBULIN A NEPHROPATHY (ISN-WCN 2025) - P3 | "Similar to the Phase 2 ENVISION study, diverse enrollment in this trial is representative of a broad population with high-risk disease and allows for evaluation of sibeprenlimab treatment across a spectrum of patients with IgAN. This trial will report clinical results at a future date."

Clinical • P3 data • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Renal Disease

Nephrology : what's new in 2024 (II) (PubMed, Rev Med Suisse) - "When treating IgA nephropathy, endothelin antagonists and sibeprenlimab have shown effectiveness in slowing the progression of chronic kidney isease...For individuals starting hemodialysis after the age of 75, there is a modest survival benefit, although it comes at the cost of reduced time spent at home. In the future, noninvasive biomarkers may enable early detection of renal graft rejection."

Biomarker • Journal • Acute Kidney Injury • Cardiovascular • Glomerulonephritis • IgA Nephropathy • Nephrology • Transplant Rejection

Trial of the Impact of Sibeprenlimab on Immunoglobulin A Nephropathy Kidney Tissue (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Biopsy • New P2 trial • Glomerulonephritis • IgA Nephropathy • Renal Disease

The Anti-APRIL Antibody Sibeprenlimab Reduces Circulating Immune Complexes in Patients with IgAN: The Phase 2 ENVISION Randomized Controlled Trial (KIDNEY WEEK 2024) - P2 | "Sibeprenlimab demonstrated robust reduction of IgG/IgA- and IgM/IgA-CICs at all study doses. In the ENVISION trial, reduction of CICs along with galactose-deficient IgA1 and uPCR over time provide further mechanistic evidence for the effects of APRIL inhibition, resulting in stabilization of kidney function as demonstrated by reduction in proteinuria and improvement in eGFR profiles. Together, these results support the disease-modifying activity of sibeprenlimab in the treatment of IgAN.1Mathur M et al., N Engl Med."

Clinical • P2 data • Glomerulonephritis • IgA Nephropathy • Renal Disease

ENVISION: sibeprenlimab in patients with IgA nephropathy (ESPN 2024) - No abstract available

Clinical • Glomerulonephritis • IgA Nephropathy • Renal Disease

Humoral Response to COVID Vaccine and Infection is Intact During Sibeprenlimab Treatment of IgAN: Data From the ENVISION Trial (UKKW 2024) - P2 | "Among 155 patients who received sibeprenlimab (n=117) or placebo (n=38), 56 (36.1%) had COVID infection reported as an AE during the study (Table 1). Overall, proportionally fewer sibeprenlimab recipients (33.3%) had a reported COVID AE compared with placebo recipients (44.7%). Two patients (one each in the sibeprenlimab and placebo groups) were hospitalized with serious COVID AEs in accordance with local management protocols; none admitted to intensive care or mechanically ventilated and there were no COVID-related deaths."

Glomerulonephritis • IgA Nephropathy • Infectious Disease • Novel Coronavirus Disease • Renal Disease • Respiratory Diseases