82% (n=9/11) of patients who received felzaltamab experienced resolution of symptoms. Antibody-mediated rejection The proportion of patients meeting the Banff criteria in the 24-week biopsy was significantly increased compared to 20% (n=2/10) in the placebo group, and patients treated with felzaltamab demonstrated reductions in disease-related biomarkers and stabilization of eGFR.
Sixty-three percent (n=7/11) of felzalutamab-treated patients achieved a microvascular inflammation (MVI) score of 0, and 100% (n=11/11) of felzalutamab-treated patients showed improvement in MVI score.
The results were published in the New England Journal of Medicine, Vol. 61.st European Society of Nephrology (ERA) Congress
The results support the advancement of felzaltamab into late-stage development as a novel treatment for antibody-mediated rejection.
South San Francisco, California, May 25, 2024 SAN FRANCISCO, Oct. 13, 2020 /PRNewswire/ — Human Immunology Biosciences (HI-Bio™), a clinical-stage biotechnology company developing targeted therapies for patients with severe immune-mediated diseases (IMDs), today announced positive results from a Phase 2 investigator-initiated clinical trial of felzalutamab for late antibody-mediated rejection (AMR) in kidney transplant patients.
Felzalutamab is an investigational monoclonal antibody designed to specifically target and deplete CD38+ cells, including plasmablasts, plasma cells, and natural killer (NK) cells, which are believed to be responsible for AMR and other IMDs. This double-blind, placebo-controlled, phase 2 study was designed to evaluate the safety and tolerability of felzalutamab in adults with late AMR ≥180 days after kidney transplantation. Patients were randomized 1:1 to receive 9 infusions of felzalutamab (16 mg/kg) or placebo over 20 weeks, followed by a 32-week observation period. Biopsies were performed at baseline, 24 weeks, and 52 weeks. The study enrolled 22 patients.
Felzalutamab demonstrated a tolerable safety and side effect profile in patients with late-stage AMR. Most adverse events were mild or moderate in severity. Mild or moderate infusion reactions occurred in patients in the felzalutamab group, usually during the first infusion (n=8). There were no treatment-related discontinuations.
Key secondary endpoints showed that felzalutamab may cure the disease according to the Banff classification, making it the first effective treatment for late AMR, an international standard for characterizing kidney transplant-related disease, including late rejection.
In the treatment group, 82% (n=9/11) of patients experienced resolution of AMR at week 24 compared with 20% (n=2/10) of patients receiving placebo. One patient receiving placebo experienced graft loss at week 14, likely due to persistent chronic active AMR. Median microvascular inflammation (MVI) scores at week 24 were lower in the felzalutamab group than in the placebo group (0 vs. 2.5), with 64% (n=7/11) of subjects receiving felzalutamab achieving an MVI score of 0. Of those who experienced resolution at week 24, 67% (n=6/9) remained drug-free at week 52. Additionally, a significant reduction in donor-derived free DNA (dd-cfDNA), a marker of allograft injury, was observed.
Compared to placebo, there was both a stabilization of eGFR, a measure of kidney function, and a reduction in NK cells, which are key mediators of downstream inflammation and tissue damage.
“There is a large unmet need for therapies that resolve Banff disease and preserve renal function in patients with antibody-mediated rejection,” said the lead investigator. Georg Bohmig“The data presented in this study are very compelling and represent a potentially major breakthrough for this burdensome disease,” said Dr.
According to the United Nations Network for Organ Donation (UNOS), there are approximately 93,000 patients on the kidney transplant waiting list in the United States. united states of americaOne in 20 patients die each year while waiting for a transplant. AMR occurs despite the use of standard immunosuppressive therapy and is the leading cause of post-transplant kidney failure, affecting approximately 23,000 transplant patients in the United States. united states of america It often leads to graft loss.Currently, there is no approved treatment for late AMR.
“We believe these data suggest that felzalutamab has the potential to help preserve the groundbreaking and often life-saving benefits of kidney transplantation by addressing a major cause of rejection,” he said. Uptal Patel“Based on the activity observed in key biomarkers of graft damage and function and the concordance of results, we remain confident in our anti-CD38 depletion strategy with felzalutamab. We intend to advance felzalutamab into later-stage studies where patients have significant unmet need in antibody-mediated rejection and other immune-mediated diseases,” said HI-Bio's chief medical officer, M.D.
The data were published simultaneously in the New England Journal of Medicine and presented as a late-breaking presentation by the lead author. Katharina MeyerMD, Department of Nephrology and Dialysis, University of Oklahoma Medical Center Vienna61st (ERA) European Association of Nephrology Stockholm.
The full ERA meeting presentations will be published on the HI-Bio website.
Antibody-Mediated Rejection (AMR) in Kidney Transplant Patients
Antibody-mediated rejection (AMR) is the leading cause of kidney transplant failure, and chronic AMR affects approximately 12% of kidney transplant recipients in the United States each year.1 AMR has emerged as a leading cause of late graft loss in kidney transplant patients, and effective treatments for chronic AMR are currently limited.2
About Felzartamab
Felzalutamab is an investigational therapeutic human monoclonal antibody targeted to CD38, a protein expressed on mature plasma cells. In clinical trials, felzalutamab has been shown to selectively deplete CD38+ plasma cells, potentially enabling applications to improve clinical outcomes in a wide range of diseases driven by pathogenic antibodies. Felzalutamab was originally developed by MorphoSys AG for the treatment of multiple myeloma. HI-Bio has exclusively licensed the development and commercialization rights to felzalutamab for all indications in all countries and regions except the United States. China (include Macau and Hong Kong and Taiwan), TJ Biopharma reserves the right to modify, revise, or discontinue use.
Felzaltamab is an investigational treatment candidate that has not yet been approved by any regulatory authority.
About HI-Bio
Human Immunology Biosciences, Inc. (HI-Bio™) was founded by ARCH Venture Partners and Monograph Capital to develop precision therapies for immune-mediated diseases and enable the next phase of clinical immunology. Inspired by the rise of targeted therapies in clinical oncology, the company is pursuing therapeutic strategies to target and deplete immune cell types that cause IMD. The company's most advanced candidate, felzalutamab, is an antibody that targets CD38 and has been shown in clinical studies to deplete CD38+ cells, including plasma cells and natural killer (NK) cells, which are involved in a variety of conditions, including antibody-mediated rejection (AMR), IgA nephropathy (IgAN), lupus nephritis (LN), and primary membranous nephropathy (PMN). Additional investors include Alpha Wave Global, Arkin Bio Capital, Jeito Capital, and Viking Global Investors.
For more information about HI-Bio, please visit home page Or follow the company LinkedIn and X.
References:
- Schinstock et al. (2018) Kidney transplantation with low-level DSA or low-positive B-flow crossmatch: an underappreciated option for highly susceptible transplant candidates (page 8). Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481511/pdf/nihms837168.pdf#page=8; Ciancio et al. (2018) Antibody-mediated rejection represents a poor prognosis in kidney transplants: results from a single center. Available at: https://onlinelibrary.wiley.com/doi/10.1111/ctr.13392
- Rodriguez-Ramirez et al. (2022) Antibody-Mediated Rejection: Prevention, Monitoring, and Treatment Dilemmas (1 page). Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9475491/
SOURCE HI-Bio
