HIS news
Phase 3b Trial Evaluates Remibrutinib vs. Omalizumab in Antihistamine-Refractory Chronic Spontaneous Urticaria
A global, randomized, double-blind phase 3b trial is assessing remibrutinib 25 mg twice daily against placebo and omalizumab 300 mg every 4 weeks in adults with chronic spontaneous urticaria inadequately controlled by second-generation H1-antihistamines. The trial includes a 52-week core phase and an optional open-label extension evaluating up to two years of remibrutinib exposure.
Novartis is conducting a multicenter, double-blind, double-dummy, parallel-group phase 3b trial (NCT06042478) to evaluate the efficacy, safety, and tolerability of remibrutinib (LOU064) 25 mg b.i.d. in adults with chronic spontaneous urticaria (CSU) whose symptoms remain inadequately controlled despite second-generation H1-antihistamine therapy. The trial is currently active but no longer recruiting.
The core phase spans 52 weeks: remibrutinib is compared against placebo over the initial 24 weeks, with omalizumab 300 mg every 4 weeks serving as an active comparator across the full 52-week period. This three-arm design allows both a placebo-controlled efficacy signal and a head-to-head benchmark against the established anti-IgE biologic standard of care in this indication.
Remibrutinib is an oral, selective Bruton's tyrosine kinase (BTK) inhibitor. By targeting BTK-dependent signaling in mast cells and basophils, it aims to suppress the downstream IgE-mediated and IgG-mediated pathways implicated in CSU pathogenesis—offering a mechanistically distinct oral alternative to injectable biologics. An optional open-label extension phase extends follow-up to approximately two years, enrolling both participants who received remibrutinib throughout the core phase and those transitioning from omalizumab at week 52. During the extension, remibrutinib is administered without background therapy, enabling assessment of monotherapy durability.
The trial's active-not-recruiting status indicates enrollment is complete and data collection is ongoing. Long-term safety and tolerability data from the extension phase will be particularly informative given the chronic, relapsing nature of CSU and the need for sustained disease control in this population.
Key points
- Phase 3b RCT evaluating remibrutinib 25 mg b.i.d. versus placebo (24-week primary comparison) and omalizumab 300 mg q4w (52-week active comparator) in H1-antihistamine-refractory CSU
- Remibrutinib is an oral selective BTK inhibitor targeting mast cell and basophil signaling pathways central to CSU pathogenesis
- Optional 52-week open-label extension assesses long-term remibrutinib monotherapy efficacy and safety, including participants transitioned from omalizumab
- Trial is active but no longer recruiting; sponsored by Novartis Pharmaceuticals (NCT06042478)
- Results could position an oral BTK inhibitor as a mechanistically distinct alternative to injectable anti-IgE therapy in refractory CSU
Why it matters
Chronic spontaneous urticaria refractory to H1-antihistamines represents a significant unmet need, with omalizumab currently the primary biologic option. Head-to-head efficacy and safety data comparing an oral BTK inhibitor to omalizumab could meaningfully expand treatment decision-making for dermatologists and allergists managing this population.