Ascentage Pharma Announces Global Registrational Phase III Study of Lisaftoclax for First-line Treatment of Patients with Higher-Risk Myelodysplastic Syndrome Cleared by US FDA and EMA
Ascentage Pharma (NASDAQ: AAPG) has received clearance from both the FDA and EMA to conduct the GLORA-4 study, a global Phase III registrational trial for lisaftoclax in combination with azacitidine. The study targets first-line treatment of higher-risk myelodysplastic syndrome (HR-MDS).
Lisaftoclax, a proprietary Bcl-2 inhibitor, is currently the only Bcl-2 inhibitor in Phase III trials for HR-MDS globally. Earlier studies showed promising results with a 75% overall response rate, significantly higher than current standard treatments. The multi-region, multi-center, randomized, double-blind trial is simultaneously enrolling patients in China, the U.S., and Europe.
If successful, lisaftoclax could become the first targeted therapy approved for HR-MDS first-line treatment since the introduction of hypomethylating agents, potentially addressing a significant unmet medical need in this field.
Ascentage Pharma (NASDAQ: AAPG) ha ottenuto l'autorizzazione sia dalla FDA che dall'EMA per condurre lo studio GLORA-4, uno studio registrativo globale di Fase III su lisaftoclax in combinazione con azacitidina. Lo studio è rivolto al trattamento di prima linea della sindrome mielodisplastica ad alto rischio (HR-MDS).
Lisaftoclax, un inibitore proprietario di Bcl-2, è attualmente l'unico inibitore di Bcl-2 in studi di Fase III per HR-MDS a livello globale. Studi precedenti hanno mostrato risultati promettenti con un tasso di risposta complessiva del 75%, significativamente superiore rispetto alle terapie standard attuali. Il trial, multicentrico, multiregionale, randomizzato e in doppio cieco, arruola simultaneamente pazienti in Cina, negli Stati Uniti e in Europa.
Se avrà successo, lisaftoclax potrebbe diventare la prima terapia mirata approvata per il trattamento di prima linea di HR-MDS dalla comparsa degli agenti ipometilanti, rispondendo potenzialmente a un importante bisogno medico insoddisfatto in questo ambito.
Ascentage Pharma (NASDAQ: AAPG) ha recibido la autorización tanto de la FDA como de la EMA para llevar a cabo el estudio GLORA-4, un ensayo registracional global de Fase III sobre lisaftoclax en combinación con azacitidina. El estudio se dirige al tratamiento de primera línea del síndrome mielodisplásico de alto riesgo (HR-MDS).
Lisaftoclax, un inhibidor propietario de Bcl-2, es actualmente el único inhibidor de Bcl-2 en ensayos de Fase III para HR-MDS a nivel mundial. Estudios anteriores mostraron resultados prometedores con una tasa de respuesta global del 75%, considerablemente superior a los tratamientos estándar actuales. El ensayo, multirregional, multicéntrico, aleatorizado y doble ciego, está reclutando simultáneamente pacientes en China, EE. UU. y Europa.
Si tiene éxito, lisaftoclax podría convertirse en la primera terapia dirigida aprobada para el tratamiento de primera línea de HR-MDS desde la introducción de los agentes hipometilantes, abordando potencialmente una importante necesidad médica no cubierta en este campo.
Ascentage Pharma (NASDAQ: AAPG)는 FDA와 EMA 양측으로부터 lisaftoclax와 azacitidine 병용요법을 평가하는 글로벌 등록용 3상 연구 GLORA-4를 수행할 허가를 받았습니다. 이 연구는 고위험 골수형성이상증후군(HR-MDS)의 1차 치료를 목표로 합니다.
Lisaftoclax는 독점적인 Bcl-2 억제제로, 현재 전 세계적으로 HR-MDS에 대해 3상 시험 중인 유일한 Bcl-2 억제제입니다. 이전 연구에서는 전체 반응률 75%라는 유망한 결과를 보여 현행 표준 치료보다 훨씬 높은 효과를 보였습니다. 이 다지역·다기관·무작위·이중맹검 시험은 중국, 미국 및 유럽에서 동시에 환자를 등록하고 있습니다.
성공할 경우 lisaftoclax는 저메틸화제 도입 이후 HR-MDS 1차 치료에 대해 승인된 첫 번째 표적 치료제가 될 수 있으며, 이 분야의 중요한 미충족 의료 수요를 해결할 가능성이 있습니다.
Ascentage Pharma (NASDAQ: AAPG) a reçu l'autorisation de la FDA et de l'EMA pour mener l'étude GLORA-4, un essai d'enregistrement mondial de phase III portant sur le lisaftoclax en association avec l'azacitidine. L'étude vise le traitement de première ligne du syndrome myélodysplasique à haut risque (HR-MDS).
Le lisaftoclax, un inhibiteur Bcl-2 propriétaire, est actuellement le seul inhibiteur de Bcl-2 en essai de phase III pour le HR-MDS au niveau mondial. Des études antérieures ont montré des résultats prometteurs avec un taux de réponse globale de 75%, nettement supérieur aux traitements standards actuels. L'essai, multirégional, multicentrique, randomisé et en double aveugle, recrute simultanément des patients en Chine, aux États-Unis et en Europe.
En cas de succès, le lisaftoclax pourrait devenir la première thérapie ciblée approuvée pour le traitement de première ligne du HR-MDS depuis l'introduction des agents hypométhylants, répondant potentiellement à un besoin médical important et non satisfait dans ce domaine.
Ascentage Pharma (NASDAQ: AAPG) hat sowohl von der FDA als auch der EMA die Zulassung erhalten, die GLORA-4-Studie durchzuführen – eine globale registratorische Phase-III-Studie zu lisaftoclax in Kombination mit Azacitidin. Die Studie zielt auf die Erstlinienbehandlung des Hochrisiko-Myelodysplastischen Syndroms (HR-MDS) ab.
Lisaftoclax, ein firmeneigener Bcl-2-Inhibitor, ist derzeit der einzige Bcl-2-Inhibitor in Phase-III-Studien für HR-MDS weltweit. Frühere Studien zeigten vielversprechende Ergebnisse mit einer Gesamtansprechrate von 75%, deutlich über den derzeitigen Standardtherapien. Die multiregionale, multizentrische, randomisierte, doppelblinde Studie rekrutiert gleichzeitig Patienten in China, den USA und Europa.
Gelingt die Studie, könnte lisaftoclax die erste zielgerichtete Therapie für die Erstlinienbehandlung von HR-MDS seit Einführung der Hypomethylierungswirkstoffe werden und damit einen erheblichen ungedeckten medizinischen Bedarf in diesem Bereich adressieren.
- Promising 75% overall response rate in earlier studies, significantly higher than current standard treatments
- First and only Bcl-2 inhibitor in Phase III trials for HR-MDS globally
- Simultaneous FDA and EMA clearance accelerates path to potential market authorization
- Favorable safety profile with low incidence of severe toxicities
- Already approved in China for CLL/SLL treatment
- Phase III trial results still pending, with no guarantee of success
- Complex patient population with multiple comorbidities may affect treatment outcomes
- Competition from existing standard treatments in the market
Insights
FDA/EMA clearance for lisaftoclax Phase III trial represents significant advancement toward first targeted therapy for higher-risk MDS in decades.
Ascentage Pharma has achieved a significant regulatory milestone with FDA and EMA clearance for GLORA-4, a global Phase III registrational trial for lisaftoclax in combination with azacitidine for first-line treatment of higher-risk myelodysplastic syndrome (HR-MDS). This represents the second registrational Phase III study for lisaftoclax to receive clearance from both regulatory bodies, marking substantial clinical development progress.
The importance of this development cannot be overstated. HR-MDS represents a critical unmet medical need with extremely limited treatment options. Current standard therapy with hypomethylating agents (HMAs) yields only 30-40% overall response rates with 10-17% complete responses. For context, lisaftoclax's earlier clinical data showed an impressive 75% overall response rate when combined with azacitidine, potentially representing a dramatic improvement.
From a clinical perspective, lisaftoclax is uniquely positioned as the only Bcl-2 inhibitor in Phase III development globally for HR-MDS. The favorable safety profile demonstrated in earlier studies is particularly important for HR-MDS patients, who tend to be elderly (median diagnosis age 70) with multiple comorbidities and depleted hematopoietic reserves.
The multinational approach to this trial—running simultaneously in China, the US, and Europe with prestigious co-investigators—significantly accelerates the development timeline. If successful, lisaftoclax could become the first targeted therapy approved for HR-MDS since the introduction of HMAs, fundamentally reshaping treatment for a disease where 40-60% of higher-risk patients progress to acute myeloid leukemia within five years, with dismal survival outcomes.
ROCKVILLE, Md. and SUZHOU, China, Aug. 17, 2025 (GLOBE NEWSWIRE) -- Ascentage Pharma (NASDAQ: AAPG; HKEX: 6855), a global, commercial stage, integrated biopharmaceutical company engaged in the discovery, development and commercialization of novel, differentiated therapies to address unmet medical needs in cancer, announced that it has received clearance by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to conduct GLORA-4 study (NCT06641414), a global registrational Phase III study of lisaftoclax (APG-2575), a proprietary Bcl-2 inhibitor, in combination with azacitidine (AZA), for the treatment of patients with newly diagnosed higher-risk myelodysplastic syndrome (HR-MDS).
This marks the second registrational Phase III study of lisaftoclax to receive clearance from both the FDA and EMA. The GLORA-4 study is simultaneously enrolling patients at participating centers in multiple countries, to accelerate the drug’s path to potential market authorization. To date, lisaftoclax is the only Bcl-2 inhibitor being advanced in a registrational Phase III trial in higher-risk MDS globally. This study, if positive, may potentially end the longstanding treatment gap in higher-risk MDS, marking yet another major milestone in the global clinical development of lisaftoclax.
Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, “Globally, we still lack targeted therapies for first-line treatment of patients with higher-risk MDS, which represents a huge unmet clinical need. Currently, hypomethylating agents (HMA) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain the primary treatment options for higher-risk MDS. In earlier studies, lisaftoclax has demonstrated promising clinical benefit and tolerability. The clearances of the GLORA-4 study by the U.S. FDA and EMA, coinciding with the approval by the China CDE, pave the way for lisaftoclax to potentially become the first Bcl-2 inhibitor approved globally for first-line treatment of higher-risk MDS and the first targeted therapy approved for this indication since the introduction of HMA, which fundamentally reshapes the treatment landscape.”
The GLORA-4 trial is being conducted simultaneously in China, the U.S., and Europe. This will significantly accelerate the clinical development of lisaftoclax in MDS and accelerate the drug’s path to potential market authorization. Moving forward, we will remain steadfastly committed to our mission of addressing unmet clinical needs in China and around the world, actively advancing our clinical programs for the benefit of more patients.”
GLORA-4 is a multi-region, multi-center, randomized, double-blind Phase III trial designed to evaluate the efficacy and safety of lisaftoclax in combination with AZA compared to placebo plus AZA in newly diagnosed adult patients with higher-risk MDS. The study was originally approved by the China CDE in 2024. Currently, the study is enrolling patients globally, with the first patients already enrolled in China and Europe. Guillermo Garcia-Manero, MD, Chair of the Department of Leukemia, The University of Texas MD Anderson Cancer Center (MDACC), and Prof. Xiaojun Huang, MD, an academician of the Chinese Academy of Engineering, director of the Institute of Hematology at Peking University, and director of the Department of Hematology at Peking University People’s Hospital, are global co-leading principal investigators of the study.
MDS is a myeloid clonal disease originating from hematopoietic stem cells with strongly age-correlated characteristics. Global epidemiological data of MDS show an exponential increase in incidence with age (22/100,000 in the population aged over 65 years), with a median age of diagnosis of 70 years1. More than
As the standard first-line therapy for higher-risk MDS, HMAs offer inadequate responses to treatment, with an overall response rate (ORR) of just 30
Lisaftoclax is a proprietary, novel, orally administered Bcl-2 selective inhibitor being developed by Ascentage Pharma to treat patients with malignancies by selectively blocking the anti-apoptotic protein Bcl-2 and restoring the normal apoptosis process in cancer cells. Lisaftoclax is already approved in China for 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.
Previously, the Company released the clinical data of lisaftoclax in combination with AZA in treatment-naïve (TN) MDS during the 2024 American Society of Hematology (ASH) Annual Meeting and the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. These data showed an ORR of
Professor Huang commented, “Despite the significant advancement in the treatment of hematologic malignancies, higher-risk MDS remains a major clinical challenge because of a range of factors. First, the current standard of care treatment with HMAs only offers limited efficacy, with just about one-third of patients achieving a response to treatment. Second, no breakthrough therapies have emerged globally in the two decades since the introduction of HMAs. As a result, there is an unmet clinical need for targeted therapies for higher-risk MDS. The compelling response rate and manageable safety profile observed in earlier studies of lisaftoclax are very encouraging. We hope this global Phase III study has the potential to provide new insights that could benefit how we treat and manage higher-risk MDS.”
Dr. Garcia-Manero commented, “Higher-risk MDS is more prevalent in older populations and thus presents unique clinical challenges. These patients often have multiple comorbidities and depleted hematopoietic reserves, making them less tolerant of treatment with particularly high requirement for safety. Preliminary clinical data of lisaftoclax demonstrated notable clinical benefit, with low rates of treatment-related dose adjustments and mortalities while maintaining significant response rates. We hope these characteristics of lisaftoclax will make it a potentially superior treatment option for patients.”
References:
- Ma X, et al. Epidemiology of myelodysplastic syndromes. Am J Hematol. 2022;97(3):354-362. doi:10.1002/ajh.26442
- Sekeres MA, et al. Comorbidities predict inferior survival in myelodysplastic syndromes. Br J Haematol. 2020;191(4):606-613. doi:10.1111/bjh.16987
- Zeidan AM, et al. Risk of acute myeloid leukemia transformation in higher-risk MDS. Blood Cancer J. 2021;11(2):32. doi:10.1038/s41408-021-00426-2
- Lindsley RC, et al. *Prognostic mutations in myelodysplastic syndromes after progression to AML. J Clin Oncol. 2017;35(15):1591-1597. doi:10.1200/JCO.2016.71.6715
- Fenaux P, et al. Azacitidine prolongs survival in higher-risk MDS. Lancet Oncol. 2009;10(3):223-232. doi:10.1016/S1470-2045(09)70003-8
- Silverman LR, et al. Randomized phase III study of azacitidine vs conventional care in higher-risk MDS. J Clin Oncol. 2011;29(18_suppl):6501. doi:10.1200/jco.2011.29.15_suppl.6501
- Deeg HJ, et al. Allogeneic stem cell transplantation for MDS: outcomes in >60 years. Biol Blood Marrow Transplant. 2018;24(2):341-346. doi:10.1016/j.bbmt.2017.10.035
- Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. International Vidaza High-Risk MDS Survival Study Group. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009 Mar;10(3):223-32. doi: 10.1016/S1470-2045(09)70003-8.
- Lisaftoclax (APG-2575), a Novel BCL-2 Inhibitor, in Combination with Azacitidine in Treatment of Patients with Myelodysplastic Syndrome (MDS). ASH 2024；
- Phase 1b/2 Study of Lisaftoclax (APG-2575) Combined with Azacitidine (AZA) in Patients with Treatment-naïve（TN）or Prior Venetoclax（VEN）-exposed Myeloid Malignancies. ASCO 2025
About Ascentage Pharma
Ascentage Pharma (NASDAQ: AAPG; HKEX: 6855) is a global, commercial stage, integrated biopharmaceutical company engaged in the discovery, development and commercialization of novel, differentiated therapies to address unmet medical needs in cancer. 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.
The second lead asset, lisaftoclax, is the first China-approved third-generation Bcl-2 inhibitor indicated 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. 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 who were 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
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Contact Information
Investor Relations:
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Ascentage Pharma
Hogan.Wan@ascentage.com
+86 512 85557777
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ICR Healthcare
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+1 (646) 277-1282
Media Relations:
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ICR Healthcare
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FAQ
What is the significance of FDA and EMA clearance for Ascentage Pharma's (AAPG) GLORA-4 study?
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What are the key features of Ascentage Pharma's GLORA-4 trial?
