Ascentage Pharma's Lisaftoclax Gets Priority Review by China's NMPA

ROCKVILLE, Md. and SUZHOU, China, Nov. 17, 2024 -- Ascentage Pharma (6855.HK), a global biopharmaceutical enterprise focused on discovering, developing, and commercializing therapies for unmet medical needs, particularly in cancer treatment, has announced that its investigational Bcl-2 selective inhibitor, lisaftoclax (APG-2575), has received acceptance for a New Drug Application (NDA) with a Priority Review designation by China’s National Medical Products Administration (NMPA). This novel drug aims to treat patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have relapsed or are refractory to other treatments. This marks the first NDA for a domestically developed Bcl-2 inhibitor in China, potentially positioning lisaftoclax as the second Bcl-2 inhibitor approved worldwide.

The NDA relies on data from a pivotal Phase II study in China, which assessed the efficacy and safety of lisaftoclax in patients with relapsed or refractory CLL/SLL. The study's primary endpoint was the overall response rate.

CLL/SLL, a type of hematologic malignancy originating from mature B-cell neoplasms, mainly affects older adults and is one of the most prevalent leukemia subtypes in the Western world, with over 100,000 new cases reported annually. In China, while the incidence rate is relatively lower, the disease is rapidly increasing, presenting at a younger age with greater aggressiveness. SLL and CLL are two different manifestations of the same disease, with around 20% of SLL cases progressing to CLL. Treatments such as immunotherapies and Bruton's tyrosine kinase inhibitors (BTKis) have significantly improved initial treatment responses. However, the complex nature of the disease and the limitations of existing treatments necessitate new, effective treatment options for patients with relapsed or refractory conditions.

Bcl-2 inhibitors have revolutionized CLL/SLL treatment by targeting the Bcl-2 protein, an apoptosis suppressor that regulates cell survival. The overexpression of Bcl-2, particularly in CLL/SLL, helps tumor cells evade apoptosis. Developing Bcl-2 as a therapeutic target is challenging due to its large binding interface and location on the mitochondrial membrane, which complicates drug delivery. Only one Bcl-2 inhibitor has been approved globally in nearly 40 years, underscoring the significant challenges in this field. While western countries have adopted chemotherapy-free regimens, no Bcl-2 inhibitor has been approved in China, highlighting the need for new therapies.

Lisaftoclax is an investigational, orally administered small-molecule Bcl-2 selective inhibitor under development by Ascentage Pharma. It aims to treat malignancies by selectively inhibiting the antiapoptotic protein Bcl-2, thereby restoring normal apoptosis in cancer cells. Lisaftoclax is the first Bcl-2 inhibitor in China and the second globally to show significant clinical benefit and enter pivotal studies. It holds potential for treating various hematologic malignancies and solid tumors, either as a single agent or in combination with other treatments.

Lisaftoclax is undergoing multiple Phase III registrational studies. These include a global study in combination with a BTKi for previously treated CLL/SLL patients; a study with acalabrutinib for first-line treatment of treatment-naïve CLL/SLL patients; a study with azacitidine (AZA) for elderly/unfit patients with acute myeloid leukemia (AML); and a study with AZA for newly diagnosed higher-risk myelodysplastic syndrome (MDS) patients.

Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma, highlighted the company's extensive experience in developing apoptosis-targeted therapies, noting the significant milestone represented by the NDA submission for lisaftoclax. He emphasized the urgent clinical need for treatments for relapsed or refractory CLL/SLL and reaffirmed Ascentage Pharma's commitment to accelerating the global development of lisaftoclax and other novel therapies to address unmet medical needs worldwide.