Biogen has initiated dosing in TRANSCEND, a global Phase 3 clinical trial evaluating felzartamab for the treatment of late antibody-mediated rejection (AMR) in kidney transplant recipients. The study will assess the efficacy and safety of this investigational CD38-targeting monoclonal antibody compared to placebo in approximately 120 adult patients.
The announcement represents a significant advancement in Biogen's immunology portfolio and offers potential hope for kidney transplant patients facing limited treatment options for this serious condition.
A Critical Unmet Need in Transplant Medicine
Antibody-mediated rejection remains one of the leading causes of kidney transplant failure, with approximately 23,000 patients living with various forms of AMR in the United States alone. Late AMR, occurring more than six months post-transplantation, poses a particularly significant challenge as it is associated with a greater risk of graft loss compared to early AMR, and effective treatment options are currently limited.
"Antibody-mediated rejection remains a significant challenge in kidney transplantation, with limited safer and effective treatment options currently available," said Dr. Suphamai Bunnapradist, principal investigator of the study and Professor of Clinical Medicine, Director of Research at Connie Frank Kidney Transplant Center, University of California, Los Angeles.
AMR occurs when the immune system recognizes the donor kidney as foreign, generating antibodies against it that can lead to destruction and eventual rejection of the transplanted organ.
TRANSCEND Trial Design and Endpoints
The TRANSCEND study is structured as a two-part, 52-week, double-blind, placebo-controlled, multicenter, randomized Phase 3 clinical trial. In Part A, participants will receive nine intravenous infusions of either felzartamab or placebo over six months, with efficacy and safety assessments conducted at 24 weeks.
The primary endpoint is the percentage of participants who achieve resolution of AMR by biopsy at 6 months. Key secondary endpoints include changes in microvascular inflammation (MVI) score and the percentage of patients achieving an MVI score of zero—a significant measure as higher MVI scores strongly correlate with reduced kidney allograft survival rates.
In Part B of the trial, all participants will receive felzartamab for an additional open-label period of six months through 52 weeks to evaluate longer-term activity, safety, and tolerability.
Mechanism of Action and Development History
Felzartamab is designed to selectively deplete CD38-positive plasma cells, potentially addressing key pathophysiologic drivers of microvascular inflammation and AMR. By targeting CD38, the drug aims to reduce pathogenic antibody-producing plasma cells and natural killer (NK) cell activity.
"With the potential to be disease-modifying based on the encouraging results observed in the Phase 2 study, I believe felzartamab could be an important new therapeutic treatment option for patients with late AMR," Dr. Bunnapradist added.
The drug was originally developed by MorphoSys AG (now MorphoSys GmbH, a Novartis company). Human Immunology Biosciences (HI-Bio) exclusively licensed the rights to develop and commercialize felzartamab across all indications in all countries and territories excluding China. Biogen acquired HI-Bio in July 2024, adding felzartamab to its late-stage immunology portfolio.
As part of the initiation of the Phase 3 trial, MorphoSys will earn a one-time milestone payment of $35 million from Biogen.
Broader Development Program
Beyond AMR, Biogen has ambitious plans for felzartamab's development. The company previously announced intentions to initiate Phase 3 trials of the drug in IgA nephropathy and primary membranous nephropathy in 2025, positioning felzartamab as a potential "pipeline-in-a-product" across multiple immune-mediated diseases.
"Building upon the promising results from the Phase 2 study, which demonstrated felzartamab's first-in-class potential, the launch of the TRANSCEND trial is a crucial milestone in the advancement of its clinical development," said Travis Murdoch, Head of HI-Bio at Biogen. "Losing a kidney after receiving a long-awaited transplant is devastating for the patient and the donor. As we enroll this pivotal Phase 3 trial, we look forward to working in collaboration with medical and patient communities worldwide with the hope of bringing felzartamab forward as potentially the first meaningful treatment option, if approved, for people living with late AMR."
Implications for Transplant Medicine
If successful, felzartamab could become the first approved treatment specifically for late AMR, addressing a significant gap in transplant medicine. For patients who have received kidney transplants after long waits, the possibility of a therapy that could prevent rejection and extend the life of their transplanted organs represents a potentially life-changing development.
The TRANSCEND trial results will be closely watched by nephrologists, transplant specialists, and patients alike, as positive outcomes could significantly impact the standard of care for kidney transplant recipients experiencing antibody-mediated rejection.
