Birelentinib granted FDA fast track designation for the treatment R/R CLL/SLL

On August 6, 2025, the U.S. Food and Drug Administration (FDA) granted fast track designation to birelentinib (DZD8586), a first-in-class, non-covalent LYN/Bruton’s tyrosine kinase (BTK) dual inhibitor with full blood–brain barrier penetration, for the treatment of adult patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have received ≥2 prior lines of therapy, including a BTK inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor.¹

This designation is based on results from a pooled analysis of the phase I TAI-SHAN5 study (NCT05824585) and the phase II TAI-SHAN8 study (NCT06539182) of birelentinib in patients with CLL/SLL previously treated with covalent/non-covalent BTK inhibitors and BTK degraders.^1,2 The overall response rate was 84.2%, with responses observed regardless of prior covalent BTKi, non-covalent BTKi, BTK degrader, and BCL-2 inhibitor treatment, as well as in patients with BTK-dependent and -independent mutations.² The estimated 9-month duration of response was 83.3%.² The safety profile of birelentinib at the 50 mg dose was deemed manageable, with no drug-related bleeding, atrial fibrillation, or major cardiac events observed.² The most common Grade ≥3 treatment-emergent adverse events at the 50 mg dose were neutropenia (26.7%) and pneumonia (6.7%).²