Biogen Launches Phase 3 Trial of Felzartamab for Late AMR in Kidney Transplants

Biogen Inc. has launched the dosing phase of its pivotal clinical trial, known as TRANSCEND, to investigate the effectiveness and safety of the experimental drug felzartamab in adult patients who have experienced late antibody-mediated rejection (AMR) following a kidney transplant. This significant step in the clinical development of felzartamab is aimed at addressing a crucial challenge in kidney transplantation, where AMR is a primary contributor to transplant loss. AMR occurs when the immune system identifies the donor kidney as foreign, leading to the production of antibodies that can attack and potentially destroy the transplanted organ. This condition is particularly severe when it emerges six months or more post-transplantation, as it is associated with a higher likelihood of graft loss compared to early AMR.

The TRANSCEND study is a large-scale, international Phase 3 trial that will enroll around 120 adult kidney transplant recipients who have developed late-stage AMR. The trial follows promising outcomes from the earlier Phase 2 study, which showcased felzartamab's potential as a pioneering treatment option. According to Travis Murdoch, the Head of Human Immunology Biosciences at Biogen, the loss of a transplanted kidney is devastating for both the recipient and the donor. He emphasized the importance of this Phase 3 trial in potentially establishing felzartamab as the first meaningful treatment for late AMR, contingent upon regulatory approval.

The study design includes a 52-week, double-blind, placebo-controlled structure conducted across multiple centers. Participants will be randomly assigned to receive either felzartamab or a placebo through nine intravenous infusions over a six-month period in the first part of the trial. The primary focus will be on assessing the resolution of AMR via biopsy at the 24-week mark. Key secondary measures include evaluating changes in the microvascular inflammation (MVI) score and determining the percentage of participants achieving an MVI score of zero. MVI is a significant histological feature of AMR, with higher scores often linked to decreased survival rates of the kidney graft.

Felzartamab is designed to target CD38, a protein found on mature plasma cells, with the goal of reducing the production and activity of antibodies and NK cells that contribute to MVI and AMR. The second phase of the TRANSCEND trial involves all participants receiving open-label felzartamab for an additional six months to further assess the drug's long-term safety and efficacy.

In addition to its efforts in AMR, Biogen aims to commence Phase 3 trials of felzartamab in other kidney-related conditions, such as IgA nephropathy and primary membranous nephropathy, within the year 2025. Originally developed by MorphoSys AG, now a part of Novartis, felzartamab was licensed to Biogen through its acquisition of Human Immunology Biosciences in 2024. For this initiation, MorphoSys is set to receive a one-time milestone payment of $35 million from Biogen.

While felzartamab has shown promise in early-stage trials, it remains an investigational drug and has not been approved by any regulatory body. The TRANSCEND study represents a critical opportunity to establish its efficacy and safety as a potential groundbreaking treatment for immune-mediated conditions, including late-stage AMR in kidney transplant patients.