Evobrutinib — Investigational Agent
BTK Inhibitor · Phase 2 · EMD Serono / Merck KGaA
Mechanism of Action
Non-covalent (reversible) BTK inhibitor. Unlike ibrutinib and acalabrutinib, evobrutinib does not form an irreversible covalent bond with Cys481 of BTK — instead it binds the active site reversibly with high selectivity. This non-covalent mechanism preserves activity against the BTK C481S resistance mutation (the dominant acquired resistance mechanism for covalent BTKi) and may reduce off-target ITK/TEC kinase inhibition, theoretically preserving cytotoxic lymphocyte function.
Investigational Indications
- Relapsed/refractory chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL/SLL)
- Relapsed/refractory diffuse large B-cell lymphoma (DLBCL)
- Relapsed/refractory follicular lymphoma
- Waldenström's macroglobulinemia
- Multiple sclerosis (separate non-oncology development program; Phase 3 did not meet primary endpoint vs teriflunomide)