Ascentage Pharma Announces Its Novel Bcl-2 Inhibitor Lisaftoclax Approved by China NMPA, Ushering in a New Era for the Treatment of CLL/SLL
Ascentage Pharma (NASDAQ: AAPG) has achieved a significant milestone with the China NMPA approval of lisaftoclax, its novel Bcl-2 inhibitor, for treating adult patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have received prior systemic therapy including BTK inhibitors.
The approval is based on a pivotal Phase II study where lisaftoclax demonstrated compelling efficacy and favorable safety profile, with no tumor-lysis syndrome and manageable toxicities. This makes lisaftoclax the first Bcl-2 inhibitor approved in China for CLL/SLL treatment and only the second globally.
The drug addresses a significant unmet need in China, where CLL/SLL incidence is rising rapidly with younger onset age. Lisaftoclax was recently included in the 2025 Chinese Society of Clinical Oncology Guidelines, and Ascentage is currently conducting four global Phase III trials exploring additional indications.
Ascentage Pharma (NASDAQ: AAPG) ha raggiunto un traguardo importante con l'approvazione da parte della NMPA cinese di lisaftoclax, il suo innovativo inibitore di Bcl-2, per il trattamento di pazienti adulti con leucemia linfatica cronica/linfoma linfocitico piccolo (CLL/SLL) che hanno ricevuto terapie sistemiche precedenti, inclusi inibitori di BTK.
L'approvazione si basa su uno studio pivotale di Fase II in cui lisaftoclax ha dimostrato un'efficacia convincente e un profilo di sicurezza favorevole, senza sindrome da lisi tumorale e con tossicità gestibili. Questo rende lisaftoclax il primo inibitore di Bcl-2 approvato in Cina per il trattamento di CLL/SLL e solo il secondo a livello globale.
Il farmaco risponde a un bisogno clinico significativo in Cina, dove l'incidenza di CLL/SLL sta aumentando rapidamente con un'età di insorgenza più giovane. Lisaftoclax è stato recentemente incluso nelle Linee guida 2025 della Società Cinese di Oncologia Clinica, e Ascentage sta attualmente conducendo quattro studi globali di Fase III per esplorare ulteriori indicazioni.
Ascentage Pharma (NASDAQ: AAPG) ha alcanzado un hito importante con la aprobación de lisaftoclax por la NMPA de China, su novedoso inhibidor de Bcl-2, para el tratamiento de pacientes adultos con leucemia linfocítica crónica/linfoma linfocítico pequeño (CLL/SLL) que han recibido terapias sistémicas previas, incluidos inhibidores de BTK.
La aprobación se basa en un estudio pivotal de Fase II donde lisaftoclax demostró una eficacia contundente y un perfil de seguridad favorable, sin síndrome de lisis tumoral y con toxicidades manejables. Esto convierte a lisaftoclax en el primer inhibidor de Bcl-2 aprobado en China para el tratamiento de CLL/SLL y solo el segundo a nivel mundial.
El medicamento responde a una necesidad clínica significativa en China, donde la incidencia de CLL/SLL está aumentando rápidamente con una edad de inicio más joven. Lisaftoclax fue recientemente incluido en las Guías 2025 de la Sociedad China de Oncología Clínica, y Ascentage está actualmente llevando a cabo cuatro ensayos globales de Fase III para explorar indicaciones adicionales.
Ascentage Pharma (NASDAQ: AAPG)는 만성 림프구성 백혈병/소림프구 림프종(CLL/SLL) 성인 환자 치료를 위한 혁신적인 Bcl-2 억제제인 리사프토클락스(lisaftoclax)의 중국 NMPA 승인이라는 중요한 성과를 달성했습니다. 이 환자들은 BTK 억제제를 포함한 이전 전신 치료를 받은 바 있습니다.
이번 승인은 중추적 2상 임상시험을 기반으로 하며, 리사프토클락스는 강력한 효능과 우수한 안전성을 입증했으며, 종양 용해 증후군 없이 독성도 관리 가능한 수준이었습니다. 이로써 리사프토클락스는 중국에서 CLL/SLL 치료를 위한 첫 번째 Bcl-2 억제제이자 전 세계적으로는 두 번째 승인을 받은 약물이 되었습니다.
이 약물은 CLL/SLL 발생률이 빠르게 증가하고 발병 연령이 낮아지는 중국 내 중요한 미충족 수요를 충족합니다. 리사프토클락스는 최근 2025년 중국 임상종양학회 가이드라인에 포함되었으며, Ascentage는 현재 4건의 글로벌 3상 임상시험을 통해 추가 적응증을 연구 중입니다.
Ascentage Pharma (NASDAQ : AAPG) a franchi une étape importante avec l'approbation par la NMPA chinoise de lisaftoclax, son nouvel inhibiteur de Bcl-2, pour le traitement des patients adultes atteints de leucémie lymphoïde chronique/lymphome lymphoïde à petites cellules (CLL/SLL) ayant déjà reçu une thérapie systémique, y compris des inhibiteurs de BTK.
Cette approbation repose sur une étude pivot de phase II où lisaftoclax a démontré une efficacité convaincante et un profil de sécurité favorable, sans syndrome de lyse tumorale et avec des toxicités maîtrisables. Cela fait de lisaftoclax le premier inhibiteur de Bcl-2 approuvé en Chine pour le traitement de la CLL/SLL et seulement le deuxième au niveau mondial.
Le médicament répond à un besoin médical important en Chine, où l'incidence de la CLL/SLL augmente rapidement avec un âge d'apparition plus jeune. Lisaftoclax a récemment été inclus dans les directives 2025 de la Société chinoise d'oncologie clinique, et Ascentage mène actuellement quatre essais mondiaux de phase III explorant d'autres indications.
Ascentage Pharma (NASDAQ: AAPG) hat einen bedeutenden Meilenstein erreicht mit der Zulassung von lisaftoclax durch die chinesische NMPA, seinem neuartigen Bcl-2-Inhibitor, zur Behandlung erwachsener Patienten mit chronischer lymphatischer Leukämie/kleinzelligem lymphatischem Lymphom (CLL/SLL), die zuvor systemische Therapien einschließlich BTK-Inhibitoren erhalten haben.
Die Zulassung basiert auf einer entscheidenden Phase-II-Studie, in der lisaftoclax eine überzeugende Wirksamkeit und ein günstiges Sicherheitsprofil zeigte, ohne Tumorlyse-Syndrom und mit gut handhabbaren Toxizitäten. Damit ist lisaftoclax der erste in China zugelassene Bcl-2-Inhibitor für die Behandlung von CLL/SLL und weltweit erst der zweite.
Das Medikament deckt einen bedeutenden ungedeckten Bedarf in China ab, wo die Inzidenz von CLL/SLL schnell ansteigt und das Erkrankungsalter jünger wird. Lisaftoclax wurde kürzlich in die Leitlinien der chinesischen Gesellschaft für klinische Onkologie 2025 aufgenommen, und Ascentage führt derzeit vier globale Phase-III-Studien zur Erforschung weiterer Indikationen durch.
- First Bcl-2 inhibitor approved in China for CLL/SLL treatment
- Demonstrated compelling efficacy in Phase II trials with favorable safety profile
- Included in 2025 CSCO Guidelines for lymphoid malignancies
- Currently in 4 global Phase III trials for expanded indications
- Addresses significant unmet medical need in China's growing CLL/SLL market
- Limited to second-line treatment after BTK inhibitor therapy
- Currently only approved in China market
Insights
Ascentage's lisaftoclax approval in China provides the first Bcl-2 inhibitor for CLL/SLL patients with significant clinical benefits.
This approval represents a significant advancement in the treatment landscape for Chinese CLL/SLL patients previously treated with BTK inhibitors. As the first Bcl-2 inhibitor approved in China for CLL/SLL and only the second globally, lisaftoclax addresses a critical treatment gap in a disease where therapeutic options have been limited.
The pivotal Phase II study demonstrated compelling efficacy with an overall response rate meeting the prespecified endpoint in patients previously treated with BTK inhibitors and/or immunochemotherapy. What's particularly noteworthy is the favorable safety profile - no tumor lysis syndrome occurred during the study, a common and potentially fatal complication with Bcl-2 inhibitors. Additionally, there was a low incidence of manageable hematologic toxicities and mostly grade 1-2 non-hematologic toxicities.
From a mechanistic perspective, lisaftoclax works by selectively blocking the antiapoptotic protein Bcl-2, effectively restoring normal cell death processes in cancer cells. This mechanism is particularly relevant in CLL/SLL where Bcl-2 overexpression is a key factor in disease progression. The development of effective Bcl-2 inhibitors has been challenging due to protein-protein interaction complexities and mitochondrial membrane penetration requirements.
Notably, lisaftoclax is already included in the 2025 Chinese Society of Clinical Oncology Guidelines for lymphoid malignancies, validating its clinical importance. The company is conducting four global Phase III trials exploring expanded indications, suggesting broader therapeutic potential beyond the current approval.
ROCKVILLE, Md. and SUZHOU, China, July 10, 2025 (GLOBE NEWSWIRE) -- Ascentage Pharma (NASDAQ: AAPG; HKEX: 6855), a global biopharmaceutical company dedicated to addressing unmet medical needs in cancers, announced that its proprietary novel Bcl-2 selective inhibitor lisaftoclax (APG-2575) has been approved by China’s National Medical Products Administration (NMPA) for the treatment of adult patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have previously received at least one systemic therapy including Bruton’s tyrosine kinase (BTK) inhibitors, which makes lisaftoclax the first Bcl-2 inhibitor receiving conditional approval and marketing authorization for the treatment of patients with CLL/SLL in China, and the second Bcl-2 inhibitor approved globally.
Lisaftoclax is a proprietary, novel orally administered small-molecule Bcl-2 selective inhibitor developed by Ascentage Pharma to treat patients with malignancies by selectively blocking the antiapoptotic protein Bcl-2 and hence restoring the normal apoptosis process in cancer cells. In the clinical trials, lisaftoclax has shown broad therapeutic potential in multiple hematologic malignancies and solid tumors, particularly in CLL/SLL, both as a monotherapy and in combinations. Furthermore, lisaftoclax is Ascentage Pharma’s second commercialized novel drug following olverembatinib. This approval for lisaftoclax underscores Ascentage Pharma’s outstanding capabilities in global clinical development and innovation, marking another major milestone in the Company’s successful development of its deep pipeline.
This approval is based on the results from a pivotal registrational Phase II study (APG2575CC201) that was designed to evaluate the efficacy and safety of lisaftoclax monotherapy in patients with relapsed or refractory CLL/SLL, with the overall response rate (ORR) as the primary endpoint. Lisaftoclax demonstrated compelling efficacy and an ORR that met the prespecified endpoint in patients who were previously treated with BTK inhibitors and/or immunochemotherapy. Moreover, lisaftoclax showed a favorable safety profile with no tumor-lysis syndrome (TLS) occurring during the study, a low incidence of hematologic toxicities which were manageable, and a low incidence of non-hematologic toxicities which were mostly grade 1-2.
CLL/SLL is a hematologic malignancy caused by mature B-cell neoplasms. It primarily affects older populations with over 100,000 new diagnoses reported globally each year1. In China, where the incidence rate of CLL/SLL is lower than that of the western countries, the disease is occurring at a rapidly rising rate, with a younger age of onset and higher aggressiveness2. As the current primary option for the first-line treatment of CLL/SLL, BTK inhibitors have significantly improved treatment outcome for patients. However, BTK inhibitors still face a range of issues such as limited ability to induce deep responses, high risk of relapse in mid-and long-term treatment, toxicities and intolerability associated with prolonged treatment; thus, the need for safer and more effective treatment options for the patients with CLL/SLL.
The introduction of Bcl-2 inhibitors has further revolutionized the treatment of CLL/SLL. The apoptosis suppressor factor Bcl-2, commonly overexpressed in a variety of hematologic malignancies, particularly CLL/SLL, is a key mechanism by which tumor cells evade apoptosis. However, the discovery of Bcl-2 inhibitor as a therapeutic target is highly challenging mainly because its mechanism of action is based on the protein-protein interaction (PPI). The binding interface of Bcl-2 is relatively large, making it difficult for small-molecule inhibitors to exert blocking effects. Additionally, the Bcl-2 protein, located on mitochondria with double-membrane structure, is among the most complex and challenging cellular components as it requires drugs to first penetrate the cell membrane before they can further act on the mitochondrial membrane. Prior to this, no Bcl-2 inhibitor had been approved for the treatment of CLL/SLL in China. This approval for lisaftoclax fills a treatment gap in CLL/SLL, bringing renewed hope to many patients in the country.
Prof. Jianyong Li, Principal Investigator of the study from the Lymphoma Center at Jiangsu Province Hospital, noted, “CLL/SLL is a common hematologic malignancy in aging societies, and its prevalence has been steadily rising in China. Despite advancements in treatment, patients with CLL/SLL still face a range of challenges such as drug resistance, long-term medical treatment that is difficult to manage, and disappointing response rates. In recent years, drugs targeting pro-apoptotic proteins have received widespread interest in the oncology field while Bcl-2 inhibitors have emerged as a new treatment strategy for patients with CLL/SLL. Globally, Bcl-2 inhibitors have already become a key part of the treatment of CLL/SLL, but no Bcl-2 inhibitor has been approved in China up till now. This approval for the next-generation Bcl-2 inhibitor lisaftoclax represents a timely response to the urgent unmet medical need of this patient population, effectively fulfilling the void for Bcl-2 inhibitors in CLL/SLL in China. As the first China-developed Bcl-2 inhibitor, lisaftoclax has demonstrated favorable efficacy and a unique safety profile, thus providing clinicians a new treatment option that can meaningfully improve the survival of patients with CLL/SLL. In April 2025, supported by its groundbreaking efficacy and safety data in Chinese patients with CLL/SLL, lisaftoclax was included in the 2025 Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Lymphoid Malignancies. The approval and guideline recommendations for lisaftoclax, the only Bcl-2 inhibitor approved in China for the treatment of CLL/SLL, validated the drug as a safe and efficacious new treatment option, underscoring a major advancement in precision therapy for hematologic malignancies in China.”
Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, commented, “We are encouraged by the Chinese drug regulators’ recognition of lisaftoclax’s efficacy and safety, and would like to thank our investigators and their teams, and the patients for participating in the clinical study, for their efforts and trust. This approval for lisaftoclax is a milestone achieved through over a decade of committed research and clinical development by Ascentage Pharma. Lisaftoclax addresses an urgent unmet clinical need and brings a safe and effective new treatment option to patients with CLL/SLL. This represents another big step forward in our patient-centric global innovation. Lisaftoclax has broad therapeutic potential in multiple hematologic malignancies and solid tumors. We will accelerate the global development of this drug in various indications and bring it to more patients as soon as possible.”
Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma, said, “Our founding team has over 20 years of research experience in the field of apoptosis and accumulated deep expertise on the Bcl-2 target. This approval for lisaftoclax is a culmination of their dedicated research and a major milestone in our never-ending journey of innovation, further solidifying our leadership in the hematology field. As a proprietary novel drug developed through global innovation, lisaftoclax is a testament to our strength in drug development, bringing much needed change to the global landscape for Bcl-2 inhibitors. Moving forward, Ascentage Pharma will remain steadfastly committed to its mission of addressing unmet clinical needs in China and around the world and aspire to bring more innovative therapeutics to more patients globally.”
Ascentage Pharma is currently conducting 4 global registrational Phase III trials of lisaftoclax: GLORA, an FDA-cleared study of lisaftoclax in combination with BTK inhibitors for patients with CLL/SLL previously treated with BTK inhibitors for more than 12 months with suboptimal response, as well as for the patients with newly diagnosed CLL/SLL in the GLORA-2 study, with newly diagnosed, elderly and unfit acute myeloid leukemia (AML) in the GLORA-3 study, and newly diagnosed higher risk myelodysplastic syndrome (MDS) in the GLORA-4 study.
*In the United States, lisaftoclax (APG-2575) is an investigational compound and has not been approved by the US FDA.
References
- Yao, Y., Lin, X., Li, F., et al. The global burden and attributable risk factors of chronic lymphocytic leukemia in 204 countries and territories from 1990 to 2019: analysis based on the global burden of disease study 2019. Biomed Eng Online. 2022 Jan 11;21(1):4. DOI: 10.1186/s12938-021-00973-6
- Liu Peng. Practice guidelines for the diagnosis and treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma in Zhongshan Hospital, Fudan University (v1.2018). [J]. Chin J Clin Med, 2018, 25(1): 157-160. DOI 10.12015/j. issn. 1008-6358. 2018. 20180
About Ascentage Pharma
Ascentage Pharma (NASDAQ: AAPG; HKEX: 6855) is a global biopharmaceutical company dedicated to addressing unmet medical needs in cancers. The company has built a rich pipeline of innovative drug candidates that includes inhibitors targeting key proteins in the apoptotic pathway, such as Bcl-2 and MDM2-p53 and next-generation kinase inhibitors.
The lead asset, olverembatinib, is the first novel third-generation BCR-ABL1 inhibitor approved in China for the treatment of patients with CML in chronic phase (CML-CP) with T315I mutations, CML in accelerated phase (CML-AP) with T315I mutations, and CML-CP that is resistant or intolerant to first and second-generation TKIs. It is covered by the China National Reimbursement Drug List (NRDL). The Company is currently conducting an FDA-cleared, global registrational Phase III trial, or POLARIS-2, of olverembatinib for CML, as well as global registrational Phase III trials for patients with newly diagnosed Ph+ ALL and SDH-deficient GIST patients.
The second lead asset, lisaftoclax, is a novel Bcl-2 inhibitor for the treatment of various hematologic malignancies. The NDA for the treatment of relapsed and/or refractory CLL and SLL just received approval by China’s National Medical Products Administration (NMPA). The Company is currently conducting 4 global registrational Phase III trials: the GLORA study of lisaftoclax in combination with BTK inhibitors in patients with CLL/SLL previously treated with BTK inhibitors for more than 12 months with suboptimal response; the GLORA-2 study in patients with newly diagnosed CLL/SLL; the GLORA-3 study in newly diagnosed, elderly and unfit patients with AML; and the GLORA-4 study in patients with newly diagnosed higher risk MDS.
Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships and other relationships with numerous leading biotechnology and pharmaceutical companies, such as Takeda, AstraZeneca, Merck, Pfizer, and Innovent, in addition to research and development relationships with leading research institutions, such as Dana-Farber Cancer Institute, Mayo Clinic, National Cancer Institute and the University of Michigan. For more information, visit https://ascentage.com/
Forward-Looking Statements
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements, other than statements of historical facts, contained in this press release may be forward-looking statements, including statements that express Ascentage Pharma’s opinions, expectations, beliefs, plans, objectives, assumptions or projections regarding future events or future results of operations or financial condition. These forward-looking statements are subject to a number of risks and uncertainties as discussed in Ascentage Pharma’s filings with the SEC, including those set forth in the sections titled “Risk factors” and “Special note regarding forward-looking statements and industry data” in its Registration Statement on Form F-1, as amended, filed with the SEC on January 21, 2025, and the Form 20-F filed with the SEC on April 16, 2025, the sections headed “Forward-looking Statements” and “Risk Factors” in the prospectus of the Company for its Hong Kong initial public offering dated October 16, 2019, and other filings with the SEC and/or The Stock Exchange of Hong Kong Limited we made or make from time to time that may cause actual results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. The forward-looking statements contained in this presentation do not constitute profit forecast by the Company’s management.
As a result of these factors, you should not rely on these forward-looking statements as predictions of future events. The forward-looking statements contained in this press release are based on Ascentage Pharma’s current expectations and beliefs concerning future developments and their potential effects and speak only as of the date of such statements. Ascentage Pharma does not undertake any obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
Contacts
Investor Relations:
Hogan Wan, Head of IR and Strategy
Ascentage Pharma
Hogan.Wan@ascentage.com
+86 512 85557777
Stephanie Carrington
ICR Healthcare
Stephanie.Carrington@icrhealthcare.com
+1 (646) 277-1282
Media Relations:
Sean Leous
ICR Healthcare
AscentagePR@icrhealthcare.com
+1 (646) 866-4012
FAQ
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