D2.278 - Dose-response analysis of remibrutinib in oral food challenge outcomes among adults with IgE-mediated peanut allergy

Bruton’s tyrosine kinase (BTK) plays a central role in the pathophysiology of IgE-mediated diseases including food allergy.  A Phase 2 study (NCT05432388) was conducted to evaluate the safety and efficacy of remibrutinib, a highly selective, oral BTK inhibitor, at multiple dose levels in adults with IgE-mediated peanut allergy using double-blind placebo-controlled oral food challenges (DBPCFC).

Food allergy was confirmed with screening DBPCFC. Study arms consisted of either 10, 25, or 100 mg remibrutinib or placebo twice daily (bid) treatment for 4 weeks and another arm consisting of 3 weeks of placebo followed by 1 week of remibrutinib 25 mg bid treatment (1-week arm). All study arms underwent DBPCFC at the end of week 4. Responder status was defined as tolerating a single dose of ≥ 600 mg peanut protein without dose-limiting symptoms during a DBPCFC at week 4. The analysis described herein, investigated the relationship between dose, drug exposure and oral food challenge. Dose–response analysis was performed using the Multiple Comparison Procedures–Modelling (MCP-Mod) framework. Additional dose–response and dose–exposure response models were applied. The objective of this analysis was to characterize the dose–response relationship in the DBPCFC at the tested remibrutinib doses up to 100 mg bid, which also included untested intermediate doses, such as 50 mg bid and 75 mg bid.

In total 59 participants completed DBPCFC at week 4. Treatment with remibrutinib demonstrated a dose-dependent relationship, with the highest observed responder rates in the 100 mg bid arm (86.7%) and a responder rate of 63.6% in the pooled 25 mg bid arms (Figure). In the dose-response analysis, all tested models of DBPCFC consistently demonstrated a clear dose-response relationship, with suboptimal efficacy at 25 mg, and a dose-response curve beginning to plateau at 75 mg bid (Figure).

Dose-response modelling showed that remibrutinib efficacy in adults with IgE-mediated peanut allergy increased with higher doses. There was no clear differentiation of predicted responses between modelled 75 mg bid and tested 100 mg bid.