BI 655064 / AbbVie, Boehringer Ingelheim - LARVOL DELTA

Urinary exosome miRNAs as biomarkers associated with proteinuria and eGFR in lupus nephritis (ERA 2025) - " Small RNA sequencing was conducted on urinary exosome miRNAs in 93 patients with ISN/RPS class III/IV ± V LN from a trial with the anti-CD40 mAB BI655064*... Urinary exosome miRNAs might serve as mechanistic supportive biomarkers associated with proteinuria and eGFR in LN and might have the potential to be used as biomarkers to monitor treatment effects in clinical trials."

Biomarker • IO biomarker • Fibrosis • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • MIR10B • MIR143 • MIR146B • MIR17 • MIR429 • MIR509-3 • MIR574

Two-year treatment experience with BI 655064, an antagonistic anti-CD40 antibody, in patients with active lupus nephritis: An exploratory, phase II maintenance trial. (PubMed, Lupus) - "Compared with the other groups, higher rates of serious AEs (42.9% vs 23.1%-33.3%)-mainly driven by serious infections (23.8% vs 7.7%-14.3%)-and severe AEs (47.6% vs 13.3%-28.6%) were reported with BI 655064 240 mg.ConclusionsThis exploratory, phase II maintenance trial failed to demonstrate the benefits of BI 655064 on renal outcomes in the treatment of LN. However, some benefits in total and non-renal SELENA-SLEDAI scores were observed."

Journal • P2 data • Glomerulonephritis • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus

Efficacy of BI 655064 in improving renal outcome in patients with lupus nephritis. (PubMed, Arthritis Rheumatol) - No abstract available

Journal • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

Outcome of lupus nephritis patients treated with an anti-CD40 monoclonal antibody according to kidney biopsy features. (PubMed, Arthritis Rheumatol) - "In LN kidney biopsies with glomerular monocytes, high-dose BI655064 treatment improved proteinuria at 52 weeks and resulted in a higher CRR compared to biopsies without glomerular monocytes. Histologic features may guide the choice of treatment for individual LN patients."

Biopsy • Journal • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease

Outcome of Lupus Nephritis Patients Treated with a New Anti-CD40 Monoclonal Antibody According to Kidney Biopsy Features (KIDNEY WEEK 2023) - "In this post-hoc analysis, we showed that BI 655064 treatment in LN may improve the rate of proteinuria over time when monocytes are present in the biopsy, suggesting that specific renal biopsy characteristics could direct the choice of treatment for individual LN patients."

Biopsy • Clinical • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease

RELATION OF KIDNEY BIOPSY FINDINGS TO CLINICAL OUTCOMES IN PATIENTS WITH LUPUS NEPHRITIS TREATED WITH AN ANTAGONISTIC ANTI-CD40 ANTIBODY (BI 655064) (ERA-EDTA 2023) - "This post-hoc analysis of the BI 655064 trial used a novel approach which investigated whether specific histological lesions in renal biopsies were related to treatment outcome. Although the number of patients was limited, our results suggest that treatment with higher dose anti-CD40 may improve the reduction of proteinuria when monocytes are present in the biopsy. This indicates that specific information from renal biopsies could ultimately improve the choice of treatment for individual LN patients."

Biopsy • Clinical • Clinical data • Chronic Kidney Disease • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease

Clinical and biomarker responses to BI 655064, an antagonistic anti-CD40 antibody, in patients with active lupus nephritis: a randomized, double-blind, placebo-controlled, phase II trial. (PubMed, Arthritis Rheumatol) - "The trial failed to demonstrate a dose-response relationship for the primary CRR endpoint. Post-hoc analyses suggest a potential benefit of BI 655064 180mg in patients with active LN."

Biomarker • Clinical • IO biomarker • Journal • P2 data • Glomerulonephritis • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

An optimally designed anti-human CD40 antibody with potent B cell suppression for the treatment of autoimmune diseases. (PubMed, Int J Pharm) - "Previously described therapeutic antibodies targeting this pathway have various shortcomings, and the full therapeutic potential of this axis has yet to be realized. This uniquely optimized antibody targeting a highly challenging pathway was obtained by applying stringent functional and biophysical criteria during the lead selection process. BI 655064 has favorable target-mediated drug disposition (TMDD)-saturation pharmacokinetics, consistent with that of a high-quality therapeutic monoclonal antibody."

Journal • Gastroenterology • Gastrointestinal Disorder • Glomerulonephritis • Immune Modulation • Immunology • Inflammation • Inflammatory Arthritis • Inflammatory Bowel Disease • Lupus • Lupus Nephritis • Nephrology • Rheumatoid Arthritis • Rheumatology • Systemic Lupus Erythematosus • CD40 • CD40LG

An Exploratory Maintenance Trial of BI 655064 in Patients With Lupus Nephritis (clinicaltrials.gov) - P2; N=69; Completed; Sponsor: Boehringer Ingelheim; Active, not recruiting ➔ Completed

Trial completion • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

[VIRTUAL] A RANDOMISED DOSE RANGING, PLACEBO-CONTROLLED, PHASE II STUDY ASSESSING THE EFFICACY AND SAFETY OF BI 655064, AN ANTAGONISTIC ANTI-CD40 ANTIBODY, IN PATIENTS WITH LUPUS NEPHRITIS (EULAR 2021) - P2 | "The trial did not meet its primary CRR endpoint. However, when confirmation of CRR was required at both Weeks 46 and 52, the resultant decrease in the placebo response generated an effect size of 15.2% and 9.1% in favour of 180 mg and 240 mg BI 655064, respectively. Efficacy endpoints at Week 52 CRR based on 24 h proteinuria; cCRR based on UP/UC (spot urine) at Weeks 46 and 52."

Clinical • P2 data • Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Disorders • Immune Modulation • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Neutropenia • Renal Disease • CD27 • CD40LG • FAS

[VIRTUAL] A RANDOMISED DOSE RANGING, PLACEBO-CONTROLLED, PHASE II STUDY ASSESSING THE EFFICACY AND SAFETY OF BI 655064, AN ANTAGONISTIC ANTI-CD40 ANTIBODY, IN PATIENTS WITH LUPUS NEPHRITIS (ERA-EDTA 2021) - P2 | "The trial did not meet its primary CRR endpoint. However, when confirmation of CRR was required at both Wks 46 and 52, the resultant decrease in the placebo response generated an effect size of 15.2% and 9.1% in favour of 180 mg and 240 mg BI 655064, respectively. Table 1."

Clinical • P2 data • Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Disorders • Immune Modulation • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Neutropenia • Renal Disease • CD27 • CD40LG • FAS

An Exploratory Maintenance Trial of BI 655064 in Patients With Lupus Nephritis (clinicaltrials.gov) - P2; N=69; Active, not recruiting; Sponsor: Boehringer Ingelheim; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Complement-mediated Rare Disorders • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

An Exploratory Maintenance Trial of BI 655064 in Patients With Lupus Nephritis (clinicaltrials.gov) - P2; N=69; Recruiting; Sponsor: Boehringer Ingelheim; Active, not recruiting ➔ Recruiting

Clinical • Enrollment open • Complement-mediated Rare Disorders • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

An Exploratory Maintenance Trial of BI 655064 in Patients With Lupus Nephritis (clinicaltrials.gov) - P2; N=69; Active, not recruiting; Sponsor: Boehringer Ingelheim; Recruiting ➔ Active, not recruiting; N=170 ➔ 69; Trial completion date: Dec 2022 ➔ Aug 2021; Trial primary completion date: Oct 2022 ➔ May 2021

Clinical • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Complement-mediated Rare Disorders • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

Safety, Pharmacokinetics and Pharmacodynamics of BI 655064 in Phase 1 Clinical Trials in Healthy Chinese and Japanese Subjects. (PubMed, Br J Clin Pharmacol) - "BI 655064 pharmacokinetic and safety profiles in East Asian male subjects were consistent with those observed in a Western population. No adjustments in the BI 655064 dosing recommendations are warranted for future clinical trials."

Clinical • Journal • P1 data • PK/PD data • Immune Modulation • Immunology • Inflammation • Inflammatory Arthritis • Lupus

Dose Finding, Efficacy and Safety of BI 655064 in Patients With Active Lupus Nephritis (clinicaltrials.gov) - P2; N=121; Completed; Sponsor: Boehringer Ingelheim; Active, not recruiting ➔ Completed

Trial completion • Complement-mediated Rare Disorders • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis

Dose Finding, Efficacy and Safety of BI 655064 in Patients With Active Lupus Nephritis (clinicaltrials.gov) - P2; N=N/A; Active, not recruiting; Sponsor: Boehringer Ingelheim; Trial primary completion date: Dec 2019 ➔ Jun 2020

Clinical • Trial primary completion date • Complement-mediated Rare Disorders • Immunology • Lupus • Lupus Nephritis

Dose Finding, Efficacy and Safety of BI 655064 in Patients With Active Lupus Nephritis (clinicaltrials.gov) - P2; N=121; Active, not recruiting; Sponsor: Boehringer Ingelheim; Trial primary completion date: Jun 2020 ➔ Dec 2019

Clinical • Trial primary completion date • Complement-mediated Rare Disorders • Lupus • Lupus Nephritis

Dose Finding, Efficacy and Safety of BI 655064 in Patients With Active Lupus Nephritis (clinicaltrials.gov) - P2; N=120; Recruiting; Sponsor: Boehringer Ingelheim; Active, not recruiting ➔ Recruiting

Clinical • Enrollment open • Complement-mediated Rare Disorders • Lupus • Lupus Nephritis

Treatment with BI 655064 (Antagonistic Anti-CD40 Antibody) Modulates Clinical and Biomarker Parameters Associated with Rheumatoid Arthritis (RA) (ACR-ARHP 2016) - "Treatment of MTX-IR RA patients with BI 655064 resulted in moderate efficacy, which was potentially impacted by the relatively high placebo response rate and the imbalance in baseline CRP, and did not indicate any safety concerns. Treatment with BI 655064 decreased selected activated B cell subsets, inhibited RF production, and reduced levels of select circulating inflammatory and bone resorption biomarkers through 12 wks in RA patients."

P1 data • Biosimilar • Immune Modulation • Immunology • Inflammation • Rheumatoid Arthritis

Dose Finding, Efficacy and Safety of BI 655064 in Patients With Active Lupus Nephritis (clinicaltrials.gov) - P2; N=121; Active, not recruiting; Sponsor: Boehringer Ingelheim; Trial primary completion date: Dec 2019 ➔ Jun 2020

Clinical • Trial primary completion date • Complement-mediated Rare Disorders • Immunology • Lupus • Lupus Nephritis • Rare Diseases • Systemic Lupus Erythematosus

Effects of BI 655064, an antagonistic anti-CD40 antibody, on clinical and biomarker parameters in patients with active rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase IIa study. (PubMed, Ann Rheum Dis) - P1; "Although blockade of the CD40-CD40L pathway with BI 655064 in MTX-IR patients with RA resulted in marked changes in clinical and biological parameters, including reductions in activated B-cells, autoantibody production and inflammatory and bone resorption markers, with a favourable safety profile, clinical efficacy was not demonstrated in this small phase IIa study."

Biomarker • Clinical • IO Biomarker • Journal • P2a data

Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Rising Doses of BI 655064, an Antagonistic Anti-CD40 Antibody, in Healthy Subjects: A Potential Novel Treatment for Autoimmune Diseases. (PubMed, J Clin Pharmacol) - "There were no serious adverse events and the frequency and intensity of adverse events were similar for BI 655064 and placebo; no dose relationship or relevant signs of an acute immune reaction were observed. These findings support further investigation of BI 655064 as a potential treatment for autoimmune diseases."

Clinical • Journal • PK/PD data

An Exploratory Maintenance Trial of BI 655064 in Patients With Lupus Nephritis (clinicaltrials.gov) - P2; N=150; Recruiting; Sponsor: Boehringer Ingelheim; Trial completion date: Jun 2022 ➔ Dec 2022; Trial primary completion date: Mar 2022 ➔ Oct 2022

Clinical • Trial completion date • Trial primary completion date

Dose Finding, Efficacy and Safety of BI 655064 in Patients With Active Lupus Nephritis (clinicaltrials.gov) - P2; N=121; Active, not recruiting; Sponsor: Boehringer Ingelheim; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed