Therapeutic doses of efzofitimod demonstrate efficacy in pulmonary sarcoidosis

Abstract

Background In a phase 1b/2a clinical trial of efzofitimod in patients with corticosteroid-requiring pulmonary sarcoidosis, treatment resulted in dose-dependent improvement in key end-points. We undertook a post hoc analysis pooling dose arms that achieved therapeutic concentrations of efzofitimod (Therapeutic group) versus those that did not (Subtherapeutic group). Methods Peripheral blood mononuclear cells incubated with tuberculin-coated beads were exposed to varying concentrations of efzofitimod in an in vitro assay to determine concentrations that inhibited granuloma formation. In the post hoc analysis, we compared time-to-first-relapse and changes in pulmonary function after a protocolised corticosteroid taper in the Therapeutic and Subtherapeutic groups. Results Efzofitimod at ⩾300 nM (19 µg·mL−1) inhibited granuloma formation in vitro. Based on mean efzofitimod serum concentrations achieved in the phase 1b/2a study, the 3 and 5 mg·kg−1 dose arms were pooled as the Therapeutic group, while the 1 mg·kg−1 arm was pooled with the placebo arm as the Subtherapeutic group. Relapse rates were 54.4% and 7.7% in the Subtherapeutic group and Therapeutic group, respectively. Median time-to-first-relapse in the Subtherapeutic group was 126 days, whereas in the Therapeutic group, only one of 17 patients relapsed by the end of the 24-week study (p=0.017). Slopes analysis showed that forced vital capacity increased in the Therapeutic group, but decreased in the Subtherapeutic group, over the course of the trial (p=0.035). Conclusion Treatment with efzofitimod at therapeutic doses, as compared with a subtherapeutic dose or placebo, was associated with a lower rate of relapse as corticosteroids were tapered.