CD38 inhibition by felzartamab promising for resolution of antibody-mediated rejection following kidney allografts

The novel anti-CD38 antibody felzartamab has an acceptable safety profile and partially resolves antibody-mediated rejection activity following kidney allografts in a phase 2 trial.

Antibody-mediated rejection is a leading cause of allograft rejection and is associated with poor long-term outcomes in patients receiving kidney transplantation [1]. The current double-blind, parallel-group, pilot trial (NCT05021484) randomised participants following kidney allografts 1:1 to 24 weeks of felzartamab or placebo. All participants underwent a biopsy at the end of treatment (24 weeks) and another at 52 weeks. Inclusion criteria were donor-specific positive active or chronic active antibody-mediated rejection, eGFR >20 mL/min/1.73 m², and timing of the transplantation at least 6 months before study inclusion. The primary outcome was safety and tolerability, and the secondary outcomes covered the evolution of antibody-mediated rejection. Dr Katharina A. Mayer (Medical University of Vienna, Austria) presented the results [2].

With 11 participants included per treatment group, 1 placebo participant developed graft loss at week 14 due to antibody-mediated rejection. Treatment-emergent adverse events were more common with felzartamab (90.9% vs 63.6%), which could be traced back to infusion-related reactions (72.7% vs 0%). “However, the infusion-related reactions were mild-to-moderate in severity, were limited to the first dose of felzartamab and were generally easy to treat. We did not have any treatment-related discontinuations due to infusion-related reactions or any other adverse event”, highlighted Dr Mayer. The week 24 biopsy showed resolution of antibody-mediated rejection in 81.8% of participants with felzartamab versus 20.0% of participants with placebo (61.8% difference; 95% CI 18.6–100; RR 0.23; 95% CI 0.06–0.83). Of the 9 felzartamab participants showing a resolution, 33% had a recurrence of antibody-mediated rejection at the week 52 biopsy.

“We demonstrate that felzartamab had an overall acceptable safety profile when given on top of baseline immunosuppression to kidney transplant recipients”, summarised Dr Mayer. “Our preliminary efficacy data was promising and will be followed up in future trials.”

1. Irish W, et al. Transplantation. 2021;105(3):648–659.
2. Mayer KA. Randomized Phase 2 trial of felzartamab in humoral transplant rejection. Abstract #80, ERA 2024, 23–26 May, Stockholm, Sweden.

Medical writing support was provided by Mihai Surducan, PhD.

Copyright ©2024 Medicom Medical Publishers



Posted on 20 June 202424 June 2024