Evaluating rilzabrutinib in the treatment of immune thrombocytopenia.

There is an unmet need for newer treatment options in immune thrombocytopenia (ITP) that address its underlying complex immune dysregulation, induce durable platelet responses, are well tolerated, and improve fatigue and overall quality of life. Rilzabrutinib, an oral, reversible covalent Bruton tyrosine kinase (BTK) inhibitor, is effective through its multi-immune modulation mechanisms by inhibiting B-cell activation, possibly decreasing autoantibody production, preventing FcγR-mediated phagocytosis in the spleen and liver, and reducing chronic inflammation.Preclinical studies of rilzabrutinib in immune-mediated disease settings demonstrated high selectivity, full reversibility, and durable BTK occupancy. Oral rilzabrutinib 400 mg BID demonstrated rapid, durable platelet count increases in patients with persistent/chronic ITP in the phase 2 LUNA2 study and significantly improved durable platelet response vs placebo in the pivotal phase 3 LUNA3 trial. Additionally, rilzabrutinib improved multiple disease aspects including fatigue and bleeding with a well-tolerated safety profile.Through multi-immune modulation, rilzabrutinib achieves rapid and durable platelet response, improves fatigue, and decreases bleeding in ITP patients. It is well tolerated with an acceptable safety profile. Efficacy may be increased if administered earlier in the course of disease. Longer-term studies, and investigations in pediatric patients and other immune-mediated diseases are underway.