Dizal a biopharmaceutical company committed to developing novel medicines for the treatment of cancer and immunological diseases, announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation to its Birelentinib (DZD8586) for the treatment of adult patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.

Patients with CLL/SLL treated with a BTK inhibitor or a BCL-2 inhibitor often relapse or progress due to two major resistance mechanisms: BTK C481X mutations and BTK-independent activation of BCR signaling pathway. No targeted therapy currently addresses both mechanisms, posing an urgent clinical challenge. Although BTK degraders have shown encouraging anti-tumor activity in early CLL/SLL clinical studies, mutation-mediated resistance has already been reported, and degrader-associated toxicities may limit their long-term clinical application.

Birelentinib is a first-in-class, non-covalent, LYN/BTK dual inhibitor with full blood-brain barrier (BBB) penetration. It has high selectivity against other TEC family kinases (TEC, ITK, TXK and BMX). By targeting both BTK and LYN, it blocks both BTK-dependent and -independent BCR-signaling pathways, effectively inhibiting tumor growth of B-cell non-Hodgkin lymphomas (B-NHLs).

The Fast Track Designation is supported by data from a pooled analysis of two phase I/II studies of birelentinib in CLL/SLL patients previously treated with covalent/non-covalent BTK inhibitors and BTK degraders. The results were presented at 2025 European Hematology Association (EHA) Annual Congress and featured in oral presentations at both the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and the 18th International Conference on Malignant Lymphoma (ICML).

Birelentinib demonstrated significant anti-tumor efficacy in heavily pretreated CLL/SLL patients with an objective response rate (ORR) of 84.2%, with a good safety profile. Tumor responses were observed irrespective of prior treatment with covalent/non-covalent BTK inhibitors, BTK degraders, or BCL-2 inhibitors, including in patients harboring classic BTK resistance mutations (C481X) as well as other BTK mutations, such as kinase-dead mutations. Responses were durable, with an estimated 9-month duration of response (DOR) rate of 83.3%.

"The granting of Fast Track Designation underscores the U.S. FDA's recognition of birelentinib's potential to address an unmet medical need in patients with CLL/SLL," said Dr. Xiaolin Zhang, CEO of Dizal. "We look forward to working closely with the FDA to accelerate the global clinical development of birelentinib and bring this treatment option to patients as quickly as possible."

Fast Track Designation is an FDA program designed to facilitate the development and expedite the review of drugs for serious conditions that address unmet medical needs. The designation enables for frequent FDA interactions and may allow for rolling revie, priority review, or accelerated approval if criteria are met.

Source: prnewswire.com