Biogen's felzartamab, an investigational anti-CD38 monoclonal antibody, has been granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) for the treatment of late antibody-mediated rejection (AMR) without T-cell mediated rejection in kidney transplant patients. This designation aims to accelerate the development and review of felzartamab, addressing a critical unmet need in transplant medicine. The designation provides Biogen additional opportunities to engage with the FDA and supports the drug development program through Fast Track designation features.
Clinical Evidence and Rationale
The FDA's decision was supported by clinical data published in the New England Journal of Medicine and presented at the 61st European Renal Association (ERA) Congress in May 2024. These data demonstrated clinical proof of concept for felzartamab in treating AMR. A Phase 2 trial (NCT05021484) involving 22 patients with late AMR post-kidney transplant showed that 82% of patients in the felzartamab arm achieved AMR resolution at 24 weeks, compared to only 20% in the placebo group. Furthermore, 67% of the responders in the felzartamab group maintained this resolution at 52 weeks. The study also indicated a significantly lower median microvascular inflammation score in the felzartamab group (0 vs. 2.5 in the placebo group), reduced molecular markers of rejection, and decreased levels of donor-derived cell-free DNA.
Addressing Unmet Needs in Kidney Transplantation
Antibody-mediated rejection is a significant cause of kidney transplant failure, affecting approximately 12% of kidney transplant recipients in the U.S. annually. Current treatment options for chronic AMR are limited, making the development of new therapies crucial. Travis Murdoch, Head of HI-Bio at Biogen, emphasized the unmet medical need, stating, "Antibody-mediated rejection is a major reason why kidney transplants fail, and currently patients suffering from AMR have tremendous unmet medical need."
Felzartamab: A Potential First-in-Class Therapeutic
Felzartamab is an investigational human monoclonal antibody that targets CD38, a protein expressed on mature plasma cells. Clinical studies have shown that felzartamab selectively depletes CD38+ plasma cells, potentially improving clinical outcomes in diseases driven by pathogenic antibodies. Originally developed by MorphoSys for multiple myeloma, HI-Bio exclusively licensed the rights to develop and commercialize felzartamab across all indications, excluding China, before being acquired by Biogen in July 2024 for $1.15 billion upfront and up to $650 million in potential milestone payments.
Future Development Plans
Biogen plans to initiate Phase 3 trials for felzartamab across AMR, IgA nephropathy (IgAN), and primary membranous nephropathy (PMN) in 2025. Felzartamab has previously received BTD and Orphan Drug Designation (ODD) from the FDA for PMN and ODD for AMR in kidney transplant recipients, highlighting its potential in treating rare immune-mediated conditions.
Safety and Efficacy Profile
In the Phase 2 trial, mild to moderate infusion reactions were reported in eight patients in the felzartamab group. Serious adverse events occurred in one patient in the felzartamab group and four patients in the placebo group, suggesting an acceptable safety profile. However, three out of nine patients who initially responded to felzartamab experienced a recurrence of AMR, indicating a need for further investigation into long-term efficacy.
