Felzartamab Proves Safety, Potential for Therapeutic Benefit on Antibody-Mediated Rejection Following Kidney Transplant

Felzartamab had a favorable safety profile and offers the potential for therapeutic benefit among patients with antibody-mediated rejection following kidney transplantation, according to trial results presented at the 61st European Renal Association Congress.

A phase 2 trial of 22 patients with antibody-mediated rejection occurring at least 180 days after transplantation, results of the study provide an overview of the effects of the CD38 monoclonal antibody as a means to inhibit graft injury caused by alloantibodies and natural killer cells.

"There is a large unmet need for a therapy that resolves disease by the Banff Classification and preserves kidney function in patients with antibody-mediated rejection," said principal investigator Georg Böhmig, MD, associate professor of Medicine at the Division of Nephrology and Dialysis in the Department of Medicine III at the Medical University Vienna. "The data presented in this study are very compelling and represent the potential for significant progress to be made in this high burden disease."

Safety analysis of the trial indicated mild or moderate infusion reactions were identified among 8 patients in the felzartamab group compared to 0 within the placebo group. Additionally, serious adverse events were observed among 1 patient in the felzartamab group and among 4 patients in the placebo group. Investigators noted graft loss occurred in 1 patient in the placebo group.

Further analysis suggested resolution of morphologic antibody-mediated rejection occured more frequently with felzartamab than with placebo therapy (82% vs 20%), yielding a between-group difference of 62 percentage points (95% confidence interval [CI], 19 to 100; Risk Ratio [RR], 0.23; 95% confidence interval [CI], 0.06 to 0.83). Investigators pointed out the felzartamab group had a lower median microvascular inflammation score (0 vs. 2.5; difference, 1.95; 95% CI, −2.97 to −0.92), a lower molecular score reflecting the probability of antibody-mediated rejection (0.17 vs. 0.77), and a lower level of donor-derived cell-free DNA (0.31% vs. 0.82%) than was observed with placebo therapy.

Investigators also highlighted the recurrence of antibody-mediated rejection was reported in 3 of 9 patients who had a response to felzartamab week 52, with an increase in molecular activity and biomarker levels toward baseline levels.

"Based on the observed activity and concurrence of results across key biomarkers of graft damage and function, we continue to be confident in our anti-CD38 depletion strategy with felzartamab. We intend to advance felzartamab to late-stage studies in antibody-mediated rejection and other immune-mediated diseases, where patients have serious unmet needs," said Uptal Patel, MD, chief medical officer at HI-Bio

For more on the results of the study and how they inform a potential role for felzartamab among patients undergoing kidney transplant, check out our interview with Böhmig and Katharina Mayer, MD, of the Division of Nephrology and Dialysis at the Medical University of Vienna, who presented the study at ERA 24.

Relevant disclosures for Böhmig include Alexion Pharmaceuticals, Aregnx, CSL Behring, and Human Immunology Biosciences. Mayer has no relevant financial disclosures to report.

References:

1. Mayer KA, Schrezenmeier E, Diebold M, et al. A Randomized Phase 2 Trial of Felzartamab in Antibody-Mediated Rejection. New England Journal of Medicine. Published online May 25, 2024. doi:10.1056/NEJMoa2400763
2. HI-Bio. HI-Bio Announces Positive Results from Phase 2 Study of Felzartamab for Late Antibody-Mediated Rejection in Kidney Transplant Recipients. HI-Bio. May 25, 2024. Accessed May 25, 2024. https://hibio.com/news/hi-bio-announces-positive-results-from-phase-2-study-of-felzartamab-for-late-antibody-mediated-rejection-in-kidney-transplant-recipients.