At the 2025 American Society of Hematology (ASH) Congress, held on 5-9 December, results from a Phase II pivotal study for Ascentage Pharma’s BCL-2 inhibitor lisaftoclax in relapsed or refractory (R/R) chronic lymphocytic leukaemia (CLL/SLL) were presented. At the data cutoff, 63% of patients achieved a response, meeting the trial’s primary endpoint. Key secondary endpoints included a median time to response of 3.7 months and a median duration of response of 18.5 months. The 12-month progression-free survival rate was 66.4% and the 30-month overall survival rate was 78%.
In CLL, the standard first-line treatment consists of Bruton’s tyrosine kinase (BTK) inhibitors, including BeOne Medicine’s Brukinsa, AstraZeneca’s Calquence, and AbbVie’s Imbruvica. Patients who progress on BTK inhibitors generally receive AbbVie’s BCL2 inhibitor Venclexta in the second-line setting. In a cross-trial comparison, the efficacy of lisaftoclax appears comparable to Venclexta monotherapy based on post-BTK inhibitor R/R CLL studies. A key differentiator, however, is that unlike Venclexta, which requires a five-week dose escalation to mitigate tumour lysis syndrome (TLS) risk, lisaftoclax uses a daily intra-cycle ramp-up to target dose with no reported TLS events. Meanwhile, BeOne Medicine’s next-generation BCL-2 inhibitor sonrotoclax, considered more potent with a shorter half-life, has demonstrated numerically higher efficacy in a Phase II study presented at ASH in poster 5666. At a median follow-up of 14 months, there was an objective response rate of 76% and a complete response rate of 19% with no clinical TLS observed. Sonrotoclax likewise uses a rapid intra-cycle escalation strategy without a prolonged weekly ramp, reinforcing a fundamentally different TLS management profile from Venclexta. Collectively, this data positions lisaftoclax as functionally comparable to Venclexta with a potential logistical advantage driven by ramp-up and TLS management while sonrotoclax is the leading next-generation BCL-2 agent.
Go deeper with GlobalData
Access deeper industry intelligence
Experience unmatched clarity with a single platform that combines unique data, AI, and human expertise.
The drug was already approved in China earlier this year. According to leading data and analytics company GlobalData’s Pharmaceutical Intelligence Center, the likelihood of lisaftoclax gaining Food and Drug Administration (FDA) approval in the US is estimated at 24%.
Editor’s note: Reference to Ascentage seeking a US partner has been removed from this article. The company is currently funding the Phase III study without a partner.
US Tariffs are shifting - will you react or anticipate?
Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis.
By GlobalData
