Ascentage Pharma's lisaftoclax wins China BTD for first-line CLL/SLL
Ascentage Pharma has secured a Breakthrough Therapy Designation (BTD) from China's National Medical Products Administration for lisaftoclax, its oral Bcl-2 inhibitor, in combination with the BTK inhibitor acalabrutinib, for adult patients with treatment-naïve chronic lymphocytic leukaemia or small lymphocytic lymphoma. The designation was granted by the Centre for Drug Evaluation and positions the combination for an accelerated regulatory path in China, including eligibility for Priority Review and conditional approval when a New Drug Application is eventually submitted.
The news marks a second significant milestone for lisaftoclax in China in little over a year. The drug received full NMPA approval in July 2025 for relapsed or refractory CLL/SLL in patients who had previously received at least one line of therapy including a BTK inhibitor, making it the first China-developed Bcl-2 inhibitor approved in the country and only the second in the world behind AbbVie's venetoclax.
Clinical rationale
The BTD reflects genuine unmet need in the treatment-naïve setting. Current first-line options for CLL/SLL include immunochemotherapy and BTK inhibitor monotherapy, both of which carry meaningful limitations. Immunochemotherapy performs poorly in high-risk patients harbouring del(17p) or TP53 mutations, complex karyotypes, or unmutated IGHV. BTK inhibitors, while effective, require continuous dosing, are associated with long-term safety concerns, and do not always achieve sufficient depth of response. Once patients progress on these agents, subsequent options are scarce and outcomes are generally poor.
A Bcl-2 inhibitor paired with a BTK inhibitor offers a fixed-duration, chemotherapy-free combination strategy that targets apoptotic resistance through a complementary mechanism. Depth of response, measured by minimal residual disease negativity, has emerged as a key surrogate endpoint in CLL/SLL, and Bcl-2-containing doublets have demonstrated strong MRD-negativity rates in late-stage data from venetoclax-based regimens.
Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said the designation "recognises the clinical potential of lisaftoclax in combination with acalabrutinib for patients with treatment-naïve CLL/SLL and the urgent unmet need in this setting."
Competitive landscape and global programme
The pairing of a Bcl-2 inhibitor with a BTK inhibitor is well-trodden territory. AbbVie and AstraZeneca's venetoclax-acalabrutinib combination is itself under active clinical investigation, and the broader field of doublet and triplet regimens in CLL/SLL is crowded with late-stage data. Ascentage's differentiation argument rests on lisaftoclax's selectivity profile and its Chinese origin, which may offer pricing and reimbursement advantages in the domestic market.
Beyond China, Ascentage is running the global registrational GLORA-2 Phase III trial evaluating lisaftoclax plus acalabrutinib as a frontline CLL/SLL treatment, a study cleared by both the FDA and EMA. The company currently has four registrational Phase III trials running across its lisaftoclax programme, covering relapsed or refractory CLL/SLL, newly diagnosed AML, and newly diagnosed higher-risk MDS. The BTD in China does not directly accelerate the US or European timelines, but a strong domestic regulatory position may support the commercial and partnership case for the asset globally.
Investors will focus on readout timelines for GLORA-2 and on whether Ascentage can replicate the MRD-negativity benchmarks established by venetoclax-based regimens in the treatment-naïve setting. The company is dual-listed on NASDAQ and the Hong Kong Stock Exchange.