sibeprenlimab (VIS649) / Otsuka - LARVOL DELTA

Sibeprenlimab for Patients With IgA Nephropathy: Results From a Prespecified Interim Analysis of the Phase 3 VISIONARY Study (ERA 2025) - No abstract available

Clinical • Late-breaking abstract • P3 data • P3 data: top line • 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 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

Hematuria resolution with the APRIL-Blocking monoclonal antibody, Sibeprenlimab, in patients with IgA Nephropathy in a Phase 2 randomized controlled trial (UKKW 2024) - P2, P3 | "A total of 155 patients were randomized and treated (sibeprenlimab 2 mg/kg n=38; 4 mg/kg n=41; 8 mg/kg n=38; placebo n=38); 146/155 (94.2%) received all 12 treatment doses. Baseline characteristics were generally balanced between groups. Median follow up was 16.0 months."

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

Humoral Response to COVID Vaccine and Infection is Intact During Sibeprenlimab Treatment of IgAN: Data From the ENVISION Trial (ERA-EDTA 2024) - P2 | "COVID-specific antibody responses to vaccination or infection were preserved in patients with IgAN treated with sibeprenlimab. The possibility that COVID symptom presentation may have been modulated by sibeprenlimab warrants further investigation."

Critical care • Glomerulonephritis • IgA Nephropathy • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Biologics and Non-Biologics Immunosuppressive Treatments for IgA Nephropathy in Both Adults and Children. (PubMed, J Clin Med) - "Recent developments of new biologics, including anti-BAFF/APRIL inhibitors and molecules targeting complement components, offered the opportunity to selectively target immune cell subsets or activation pathways, leading to more effective and safer hypothesis-driven treatments. However, studies testing new biologic agents in IgAN should also consider paediatric populations to address the unique needs of children and close the therapeutic gap between adult and paediatric care."

Journal • Review • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Nephrology • Pediatrics • Renal Disease

Sibeprenlimab, which neutralizes a PRoliferation inducing ligand (APRIL), as a new approach to treating IgA nephropathy. (PubMed, Expert Opin Biol Ther) - P2 | "The pharmaceutical company behind sibeprenlimab is also developing it for subcutaneous use, which would have advantages over intravenous use. As IgA nephropathy is a long-term progressive disease, key questions that need to be answered, over a long-time course, with sibeprenlimab are (i) whether its safety is maintained, and (ii) whether it improves clinical outcomes."

Journal • Review • Cardiovascular • Glomerulonephritis • Hypertension • IgA Nephropathy • Infectious Disease • Nephrology • Renal Disease

Phase 2 Trial of Sibeprenlimab in Patients with IgA Nephropathy. (PubMed, N Engl J Med) - No abstract available

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

Phase 2 Trial of Sibeprenlimab in Patients with IgA Nephropathy. Reply. (PubMed, N Engl J Med) - No abstract available

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

HEMATURIA RESOLUTION WITH THE APRIL- BLOCKING MONOCLONAL ANTIBODY, SIBEPRENLIMAB, IN PATIENTS WITH IgA NEPHROPATHY IN A PHASE 2 RANDOMIZED CONTROLLED TRIAL (ISN-WCN 2024) - P2, P3 | "This Phase 2 study of patients with IgAN demonstrated robust hematuria resolution by sibeprenlimab at all study doses from Months 9 through 16, while in the placebo group hematuria persisted throughout the study. Observed resolution in hematuria, proteinuria, and eGFR profiles over time indicate that APRIL blockade with sibeprenlimab may stabilize kidney function, likely through reduction of glomerular inflammation. These results suggest a favorable efficacy and safety profile of sibeprenlimab as a disease-modifying agent in IgAN and support its further evaluation in an ongoing global Phase 3 trial (NCT05248646)."

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

Visionary Study: Phase 3 Trial of Sibeprenlimab in Immunoglobulin A Nephropathy (IgAN) (clinicaltrials.gov) - P3 | N=530 | Active, not recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Glomerulonephritis • IgA Nephropathy • Renal Disease

Sibeprenlimab Receives U.S. FDA Breakthrough Therapy Designation for the Treatment of Immunoglobulin A Nephropathy (Businesswire) - "Otsuka Pharmaceutical Development & Commercialization, Inc...announce that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for the investigational drug sibeprenlimab for the treatment of immunoglobulin A nephropathy (IgAN; Berger’s disease)....we look forward to completion of the Phase 3 trial and submission of the Biological Licensing Application (BLA) to the US FDA and other global regulatory authorities."

BLA • Breakthrough therapy designation • Regulatory • Trial status • IgA Nephropathy

Immunoglobulin A nephropathy-New treatment possibilities (PubMed, Inn Med (Heidelb)) - "While systemic corticosteroids are now only indicated in rare cases, a special budesonide formulation shows good effects. These include, among others, the dual endothelin type A receptor and angiotensin II receptor antagonist sparsentan, which has already been shown to reduce proteinuria as well as inhibitors of complement activation, which is important for kidney damage. Initial findings for these as well as for the B‑lymphocyte proliferation inhibitor sibeprenlimab, suggest that they could enrich the armamentarium for the treatment of IgA nephropathy in the future."

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

The contribution of a proliferation-inducing ligand (APRIL) and other TNF superfamily members in pathogenesis and progression of IgA nephropathy. (PubMed, Clin Kidney J) - "Several novel experimental agents targeting APRIL, including atacicept, telitacicept, zigakibart and sibeprenlimab, are currently under investigation as potential therapies in IgAN. Preliminary results suggest that these agents are well-tolerated, and reduce levels of Gd-IgA1, with corresponding improvement in proteinuria. Further studies are ongoing to confirm the safety and efficacy of anti-APRIL approaches as an effective therapeutic strategy in IgAN."

Journal • Review • Glomerulonephritis • IgA Nephropathy • Inflammation • Renal Disease • TNFRSF13B • TNFRSF1B • TNFSF13

A narrative review of potential drug treatments for nephritis in children with IgA vasculitis (HSP). (PubMed, Clin Rheumatol) - "Novel drugs that may be considered for use in early nephritis include TRF-budesonide; B-cell inhibiting agents including belimumab, telitacicept, blisibimod, VIS649, and BION-1301; B-cell depleting agents such as rituximab, ofatumumab, and bortezomib; sparsentan; angiotensin converting enzyme inhibitors (ACE-Is); and complement pathway inhibitors including avacopan, iptacopan, and narsoplimab. • Novel treatments currently being trialled in IgA nephropathy may have benefit in IgA vasculitis due to the similarities in the underlying pathophysiology, such as TRF-budesonide, B-cell modulators, and complement inhibitors. • Further studies, including clinical trials of novel drugs, are urgently needed to improve the long-term outcomes for children with IgA vasculitis nephritis."

Journal • Review • Glomerulonephritis • IgA Nephropathy • Inflammation • Nephrology • Renal Disease • Vasculitis

A Phase 2 Trial of Sibeprenlimab in Patients with IgA Nephropathy. (PubMed, N Engl J Med) - P2 | "In patients with IgA nephropathy, 12 months of treatment with sibeprenlimab resulted in a significantly greater decrease in proteinuria than placebo. (Funded by Visterra; ENVISION ClinicalTrials.gov number, NCT04287985; EudraCT number, 2019-002531-29.)."

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