Core Viewpoint - The announcement highlights the approval of the global Phase III clinical trial (GLORA-4) for the Bcl-2 selective inhibitor, Lisatoclax (APG-2575), in combination with Azacitidine (AZA) for treating newly diagnosed high-risk myelodysplastic syndromes (HR-MDS) patients, marking a significant milestone in the drug's global clinical development [1][2]. Group 1: Clinical Trial Details - GLORA-4 is an international, multicenter, randomized, double-blind Phase III clinical trial aimed at evaluating the efficacy and safety of Lisatoclax combined with AZA compared to placebo plus AZA in adult HR-MDS patients [2]. - The trial has received clinical trial approval from the CDE in 2024 and is currently enrolling patients globally, with the first patients enrolled in China and Europe [2]. - Leading principal investigators include Professor Garcia Manero from MD Anderson Cancer Center and Professor Huang Xiaojun from Peking University [2]. Group 2: Disease Background and Treatment Challenges - Myelodysplastic syndromes (MDS) are hematopoietic clonal proliferative diseases with significant age-related characteristics, showing an exponential increase in incidence with age, particularly affecting those over 65 years [2]. - The core risk of MDS is the transformation to acute myeloid leukemia (AML), with a 5-year transformation rate of 40-60% in high-risk patients, leading to poor prognosis [2]. Group 3: Current Treatment Landscape - Current first-line treatment options for high-risk MDS, such as hypomethylating agents (HMAs), have an overall response rate (ORR) of only 30-40% and a complete response (CR) rate of 10-17%, with a median duration of response of 9-12 months [3]. - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers potential cure but is limited by patient age, complex conditions, and a transplant-related mortality (TRM) rate of 25-35%, making only 5-10% of patients suitable for transplantation [3]. Group 4: Drug Profile and Efficacy - Lisatoclax is a novel oral Bcl-2 selective inhibitor developed by the company, designed to restore normal apoptosis in cancer cells by selectively inhibiting the Bcl-2 protein [3]. - The drug has already been approved in China for use in adult chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) patients who have undergone at least one prior systemic therapy [3]. - Preliminary data from the 2024 American Society of Hematology (ASH) and 2025 American Society of Clinical Oncology (ASCO) meetings indicate that Lisatoclax combined with AZA achieved an ORR of 75% in treatment-naive MDS, significantly outperforming HMAs, with a favorable safety profile [4].
亚盛医药-B：利生妥 一线治疗中高危MDS患者的全球注册III期临床研究获美国FDA和欧洲EMA批准