bleselumab (ASKP1240) / Astellas, Kyowa Kirin - LARVOL DELTA

Costimulation blockade: the next generation. (PubMed, Curr Opin Organ Transplant) - "The focus in transplantation is shifting toward safer, long-term therapies with greater accessibility. Investigational agents with subcutaneous delivery methods could overcome logistical challenges, improve adherence, and redefine posttransplant care. These advancements in costimulation blockade may enhance long-term graft survival and transform the management of KT recipients."

Journal • Cardiovascular • Transplantation • CD40LG

Study to Assess the Efficacy and Safety of Bleselumab in Preventing the Recurrence of Focal Segmental Glomerulosclerosis in de Novo Kidney Transplant Recipients (clinicaltrials.gov) - P2 | N=67 | Completed | Sponsor: Astellas Pharma Global Development, Inc. | Phase classification: P2a ➔ P2

Phase classification • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Transplantation

New Developments and Therapeutic Drug Monitoring Options in Costimulatory Blockade in Solid Organ Transplantation: A Systematic Critical Review. (PubMed, Ther Drug Monit) - "The routine use of costimulation blockade in SOT is hindered by problems in efficacy compared with the standard of care. Costimulatory inhibitors could be combined in a calcineurin inhibitor-free regimen. Future PK/pharmacodynamic studies in costimulatory agents and personalized medicine could warrant TDM of these agents."

Journal • Review • Hepatology • Solid Organ Transplantation • Transplantation • CD40LG • CD80 • TNFSF4

Efficacy and Safety of Bleselumab in Preventing the Recurrence of Primary Focal Segmental Glomerulosclerosis in Kidney Transplant Recipients: A Phase 2a, Randomized, Multicenter Study. (PubMed, Transplantation) - "In at-risk kidney transplant recipients, bleselumab numerically reduced proteinuria occurrence versus SOC, but no notable difference in occurrence of biopsy-proven rFSGS was observed."

Clinical • Journal • P2a data • Chronic Kidney Disease • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Nephrology • Transplantation

Crystal structures of human CD40 in complex with monoclonal antibodies dacetuzumab and bleselumab. (PubMed, Biochem Biophys Res Commun) - "Our results offer important insights for future structural and functional studies of CD40 and provide clues to understanding the mechanism of biological response. These data can be applied to developing new strategies for designing antibodies with more therapeutic efficacy."

Journal • Oncology • CD40 • CD40LG • TNFA

Efficacy and Safety of Bleselumab in Preventing the Recurrence of Primary Focal Segmental Glomerulosclerosis in Kidney Transplant Recipients: A Phase 2a, Randomized, Multicenter Study. (PubMed, Transplantation) - "In at-risk kidney transplant recipients, bleselumab numerically reduced proteinuria occurrence versus SOC, but no notable difference in occurrence of biopsy-proven rFSGS was observed."

Clinical • Journal • P2a data • Chronic Kidney Disease • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Nephrology • Transplantation

A Multiple Dose Escalation Study of ASKP1240 in Subjects With Moderate to Severe Plaque Psoriasis (clinicaltrials.gov) - P2 | N=60 | Completed | Sponsor: Astellas Pharma Global Development, Inc. | Phase classification: P2a ➔ P2

Phase classification • Dermatology • Immunology • Psoriasis • CD40

A Study to Assess Pharmacokinetic, Pharmacodynamic, Safety and Tolerability of ASKP1240 in de Novo Kidney Transplantation (clinicaltrials.gov) - P1 | N=50 | Completed | Sponsor: Astellas Pharma Inc | Phase classification: P1b ➔ P1

Phase classification • Transplantation

A Study to Assess the Efficacy and Safety of ASKP1240 in de Novo Kidney Transplant Recipients (clinicaltrials.gov) - P2 | N=149 | Completed | Sponsor: Astellas Pharma Global Development, Inc. | Phase classification: P2a ➔ P2

Phase classification • Transplantation

Comparative Safety and Efficacy of Immunosuppressive Regimens Post-kidney Transplant: A Systematic Review. (PubMed, Cureus) - "Other drug groups such as the mammalian target of rapamycin (mTOR) inhibitors, belatacept, and bleselumab have been used to either substitute calcineurin inhibitors or reduce their exposure...Based on these findings, a regimen containing once-daily tacrolimus and an mTOR inhibitor with or without corticosteroid is a viable immunosuppressive regimen post-kidney transplant. Further trials, especially ones with longer follow-up periods, are needed to explore these regimens' long-term safety and efficacy."

Journal • Review • Diabetes • Metabolic Disorders • Nephrology • Solid Organ Transplantation • Transplant Rejection • Transplantation

Efficacy and Safety of Tacrolimus-Based Maintenance Regimens in De Novo Kidney Transplant Recipients: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. (PubMed, Ann Transplant) - "Of 21 publications reporting graft rejection following Advagraf or Prograf treatment in ≥1 study arm, 12-month biopsy-proven acute rejection (BPAR) ranged from 3.3% with Prograf to 55.0% with mycophenolic acid (MPA)+corticosteroids (CS); >24 month BPAR ranged from 0% to 58.7% (the latter with bleselumab-based therapy). CONCLUSIONS Graft loss and patient mortality rates were generally comparable between Advagraf- and Prograf-based regimens. Further prospective studies are needed to evaluate longer-term outcomes."

Clinical • Journal • Retrospective data • Review • Cytomegalovirus Infection • Diabetes • Infectious Disease • Metabolic Disorders • Transplant Rejection • Transplantation

Study to Assess the Efficacy and Safety of Bleselumab in Preventing the Recurrence of Focal Segmental Glomerulosclerosis in de Novo Kidney Transplant Recipients (clinicaltrials.gov) - P2a; N=71; Completed; Sponsor: Astellas Pharma Global Development, Inc.; Active, not recruiting ➔ Completed; Trial completion date: Oct 2021 ➔ May 2021

Clinical • Trial completion • Trial completion date • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Transplantation

A Multiple Dose Escalation Study of ASKP1240 in Subjects With Moderate to Severe Plaque Psoriasis (clinicaltrials.gov) - P2; N=60; Active, not recruiting; Sponsor: Astellas Pharma Global Development, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Dermatology • Immunology • Psoriasis • CD40

A Multiple Dose Escalation Study of ASKP1240 in Subjects With Moderate to Severe Plaque Psoriasis (clinicaltrials.gov) - P2; N=60; Active, not recruiting; Sponsor: Astellas Pharma Global Development, Inc.

Clinical • New P2 trial • Dermatology • Immunology • Psoriasis • CD40

A Multiple Dose Escalation Study of ASKP1240 in Subjects With Moderate to Severe Plaque Psoriasis (clinicaltrials.gov) - P2; N=60; Completed; Sponsor: Astellas Pharma Global Development, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Dermatology • Immunology • Psoriasis • CD40

Study to Assess the Efficacy and Safety of Bleselumab in Preventing the Recurrence of Focal Segmental Glomerulosclerosis in de Novo Kidney Transplant Recipients (clinicaltrials.gov) - P2a; N=71; Active, not recruiting; Sponsor: Astellas Pharma Global Development, Inc.; Recruiting ➔ Active, not recruiting; Trial primary completion date: Apr 2021 ➔ Dec 2020

Clinical • Enrollment closed • Trial primary completion date • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Renal Disease • Transplantation

Study to Assess the Efficacy and Safety of Bleselumab in Preventing the Recurrence of Focal Segmental Glomerulosclerosis in de Novo Kidney Transplant Recipients (clinicaltrials.gov) - P2a; N=60; Recruiting; Sponsor: Astellas Pharma Global Development, Inc.; Trial completion date: Apr 2021 ➔ Jan 2022; Trial primary completion date: Jul 2020 ➔ Apr 2021

Trial completion date • Trial primary completion date • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Renal Disease • Transplantation

Study to Assess the Efficacy and Safety of Bleselumab in Preventing the Recurrence of Focal Segmental Glomerulosclerosis in de Novo Kidney Transplant Recipients (clinicaltrials.gov) - P2a; N=60; Recruiting; Sponsor: Astellas Pharma Global Development, Inc.; Active, not recruiting ➔ Recruiting

Clinical • Enrollment open • Chronic Kidney Disease • Diabetic Nephropathy • Focal Segmental Glomerulosclerosis • Renal Disease • Transplantation

Study to Assess the Efficacy and Safety of Bleselumab in Preventing the Recurrence of Focal Segmental Glomerulosclerosis in de Novo Kidney Transplant Recipients (clinicaltrials.gov) - P2a; N=60; Recruiting; Sponsor: Astellas Pharma Global Development, Inc.; Initiation date: Dec 2016 ➔ May 2017

Trial initiation date • Biosimilar • Chronic Kidney Disease • Diabetic Nephropathy • Focal Segmental Glomerulosclerosis • Immunology

Study to Assess the Efficacy and Safety of Bleselumab in Preventing the Recurrence of Focal Segmental Glomerulosclerosis in de Novo Kidney Transplant Recipients (clinicaltrials.gov) - P2a; N=60; Active, not recruiting; Sponsor: Astellas Pharma Global Development, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Chronic Kidney Disease • Diabetic Nephropathy • Focal Segmental Glomerulosclerosis • Renal Disease • Transplantation

A Study to Assess Pharmacokinetic, Pharmacodynamic, Safety and Tolerability of ASKP1240 in de Novo Kidney Transplantation (clinicaltrials.gov) - P1b; N=50; Completed; Sponsor: Astellas Pharma Inc; Phase classification: P1 ➔ P1b

Clinical • Phase classification

"@LVRiella : Is bleselumab a novel candidate for transplant or is it being repurposed for transplant?" (@gratefull080504)

Efficacy and safety of bleselumab in kidney transplant recipients: A phase 2, randomized, open-label, noninferiority study. (PubMed, Am J Transplant) - "Transplant recipients were randomized (1:1:1) to standard of care (SoC: 0.1 mg/kg/day immediate-release tacrolimus [IR-TAC]; target minimum blood concentration (C ) 4-11 ng/mL] plus 1 g mycophenolate mofetil [MMF] twice daily), or bleselumab (200 mg on days 0/7/14/28/42/56/70/90, and monthly thereafter) plus either MMF or IR-TAC (0.1 mg/kg/day; target C  4-11 ng/mL days 0-30, then 2-5 ng/mL). All received basiliximab induction (20 mg pre-transplant and on Day 3-5 post-transplant) and corticosteroids...Bleselumab had a favorable benefit-risk ratio. Most treatment-emergent adverse events were as expected for kidney transplant recipients."

Clinical • Head-to-Head • Journal • P2 data

A randomized, phase 1b study of the pharmacokinetics, pharmacodynamics, safety, and tolerability of bleselumab, a fully human, anti-CD40 monoclonal antibody, in kidney transplantation. (PubMed, Am J Transplant) - "Treatment-emergent anti-bleselumab antibodies were found in one kidney transplant recipient in the bleselumab 50 mg group; these were only detected at Day 7. Overall, bleselumab demonstrated non-linear pharmacokinetics and dose-dependent prolonged B-cell CD40 receptor occupancy, and was well tolerated at all doses."

Clinical • Journal • P1 data • PK/PD data

Study to Assess the Efficacy and Safety of Bleselumab in Preventing the Recurrence of Focal Segmental Glomerulosclerosis in de Novo Kidney Transplant Recipients (clinicaltrials.gov) - P2a; N=60; Recruiting; Sponsor: Astellas Pharma Global Development, Inc.; Trial completion date: May 2020 ➔ Apr 2021; Trial primary completion date: Sep 2019 ➔ Jul 2020

Clinical • Trial completion date • Trial primary completion date