D2.283 - Efficacy and safety of remibrutinib in adults with IgE-mediated peanut allergy: A Phase 2 study

Activation of Bruton’s tyrosine kinase (BTK) plays a key role in the pathophysiology of IgE-mediated conditions, including peanut 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 during screening using a DBPCFC. Study arms consisted of either 10, 25, or 100 mg remibrutinib or placebo twice daily (bid) treatment for 4 weeks and another arm of 3 weeks of placebo followed by 1 week of remibrutinib 25 mg bid treatment. All study arms underwent DBPCFC at the end of week 4. This analysis of secondary endpoints evaluated the efficacy of remibrutinib vs placebo by (1) proportion of responders who could tolerate a single dose of 1000 mg (2044 mg cumulative tolerated dose) of peanut protein without dose-limiting symptoms during the DBPCFC at week 4; and (2) proportion of responders who could tolerate a single dose of 3000 mg (5044 mg cumulative tolerated dose) of peanut protein without dose-limiting symptoms during the DBPCFC at week 4.

In total 59 participants completed the DBPCFC at week 4. Among participants who tolerated a single dose of 1000 mg peanut protein in a DBPCFC, after 4 weeks of treatment, the highest proportion of responders was observed in the remibrutinib 100 mg bid arm (Table). Interestingly, the 3 weeks placebo + 1 week remibrutinib arm also showed clinically relevant, significant improvements over placebo in the proportion of responders tolerating 1000 mg: all participants who completed DBPCFC at week 4 (6/6) were responders vs no responders in the placebo arm (Table). As expected, the proportions of responders observed at the higher single dose of 3000 mg peanut protein were lower overall (Table). Remibrutinib was generally well tolerated across doses, with an adverse event profile consistent with prior experience and comparable to placebo.

Remibrutinib may increase tolerance to peanut protein in adults with confirmed IgE-mediated peanut allergy, with early improvements evident after one week of treatment.