Olverembatinib Granted Breakthrough Therapy Designation for the Treatment of Philadelphia Chromosome-Positive (Ph+) Acute Lymphoblastic Leukemia (ALL)
Ascentage Pharma (NASDAQ: AAPG) announced that its drug olverembatinib received its third Breakthrough Therapy Designation (BTD) from China's NMPA for combination with low-intensity chemotherapy in treating newly-diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) patients.
This milestone follows previous BTDs granted in March 2021 for chronic-phase chronic myeloid leukemia and June 2023 for SDH-deficient gastrointestinal stromal tumor treatment. The BTD status prioritizes development and review processes, potentially enabling Priority Review and conditional approvals.
Ph+ ALL represents 20-30% of adult ALL cases in China, with an incidence rate of 0.69/100,000. Olverembatinib, China's first approved third-generation BCR-ABL inhibitor, is currently included in China's National Reimbursement Drug List for existing indications. A global Phase III study comparing olverembatinib plus chemotherapy versus imatinib plus chemotherapy in naïve Ph+ ALL patients was cleared in July 2023.
Ascentage Pharma (NASDAQ: AAPG) ha annunciato che il suo farmaco olverembatinib ha ricevuto la sua terza Designazione di Terapia Innovativa (BTD) dalla NMPA cinese per l'uso in combinazione con chemioterapia a bassa intensità nel trattamento di pazienti adulti recentemente diagnosticati con leucemia linfoblastica acuta (ALL) positiva al cromosoma Philadelphia (Ph+).
Questo traguardo segue le precedenti BTD concesse a marzo 2021 per la leucemia mieloide cronica in fase cronica e a giugno 2023 per il trattamento del tumore stromale gastrointestinale carente di SDH. Lo stato di BTD prioritizza i processi di sviluppo e revisione, potenzialmente consentendo una Revisione Prioritaria e approvazioni condizionate.
La ALL Ph+ rappresenta il 20-30% dei casi di ALL negli adulti in Cina, con un tasso di incidenza di 0,69/100.000. Olverembatinib, il primo inibitore BCR-ABL di terza generazione approvato in Cina, è attualmente incluso nell'elenco nazionale dei farmaci rimborsabili per indicazioni esistenti. Uno studio globale di Fase III che confronta olverembatinib più chemioterapia contro imatinib più chemioterapia in pazienti naïve con ALL Ph+ è stato approvato a luglio 2023.
Ascentage Pharma (NASDAQ: AAPG) anunció que su medicamento olverembatinib recibió su tercera Designación de Terapia Innovadora (BTD) por parte de la NMPA de China para su uso en combinación con quimioterapia de baja intensidad en el tratamiento de pacientes adultos recién diagnosticados con leucemia linfoblástica aguda (ALL) positiva para el cromosoma Filadelfia (Ph+).
Este hito sigue a las anteriores BTD otorgadas en marzo de 2021 para leucemia mieloide crónica en fase crónica y en junio de 2023 para el tratamiento de tumores estromales gastrointestinales deficientes en SDH. El estado de BTD prioriza los procesos de desarrollo y revisión, lo que potencialmente permite una Revisión Prioritaria y aprobaciones condicionales.
La ALL Ph+ representa el 20-30% de los casos de ALL en adultos en China, con una tasa de incidencia de 0.69/100,000. Olverembatinib, el primer inhibidor BCR-ABL de tercera generación aprobado en China, está actualmente incluido en la Lista Nacional de Medicamentos Reembolsables de China para indicaciones existentes. Un estudio global de Fase III que compara olverembatinib más quimioterapia frente a imatinib más quimioterapia en pacientes naïve con ALL Ph+ fue aprobado en julio de 2023.
Ascentage Pharma (NASDAQ: AAPG)는 자사의 약물 olverembatinib가 중국 NMPA로부터 저강도 화학요법과의 병용 치료를 위한 필라델피아 염색체 양성(Ph+) 급성 림프구성 백혈병(ALL) 환자 치료에 대해 세 번째 혁신 치료 지정(BTD)을 받았다고 발표했습니다.
이번 이정표는 2021년 3월 만성기 만성 골수성 백혈병에 대한 BTD와 2023년 6월 SDH 결핍 위장관 기질 종양 치료에 대한 BTD에 이어 이루어진 것입니다. BTD 지위는 개발 및 검토 프로세스를 우선시하여, 우선 검토 및 조건부 승인 가능성을 높입니다.
Ph+ ALL은 중국 성인 ALL 사례의 20-30%를 차지하며, 발생률은 0.69/100,000입니다. Olverembatinib은 중국에서 승인된 첫 번째 3세대 BCR-ABL 억제제로, 현재 기존 적응증에 대해 중국의 국가 재정 지원 약물 목록에 포함되어 있습니다. 2023년 7월에는 Ph+ ALL 환자에서 olverembatinib과 화학요법의 병용 치료를 imatinib과 화학요법의 병용 치료와 비교하는 글로벌 3상 연구가 승인을 받았습니다.
Ascentage Pharma (NASDAQ: AAPG) a annoncé que son médicament olverembatinib a reçu sa troisième désignation de thérapie révolutionnaire (BTD) de la part de la NMPA chinoise pour une utilisation en combinaison avec une chimiothérapie de faible intensité dans le traitement des patients adultes récemment diagnostiqués avec une leucémie lymphoblastique aiguë (ALL) positive pour le chromosome Philadelphia (Ph+).
Cette étape fait suite à des BTD précédemment accordées en mars 2021 pour la leucémie myéloïde chronique en phase chronique et en juin 2023 pour le traitement des tumeurs stromales gastro-intestinales déficientes en SDH. Le statut BTD priorise les processus de développement et d'examen, permettant potentiellement un examen prioritaire et des approbations conditionnelles.
La ALL Ph+ représente 20-30 % des cas d'ALL chez les adultes en Chine, avec un taux d'incidence de 0,69/100 000. Olverembatinib, le premier inhibiteur BCR-ABL de troisième génération approuvé en Chine, est actuellement inclus dans la liste nationale des médicaments remboursables pour des indications existantes. Une étude mondiale de phase III comparant olverembatinib plus chimiothérapie à imatinib plus chimiothérapie chez des patients naïfs atteints de ALL Ph+ a été approuvée en juillet 2023.
Ascentage Pharma (NASDAQ: AAPG) gab bekannt, dass sein Medikament olverembatinib von der NMPA in China die dritte Breakthrough Therapy Designation (BTD) für die Kombination mit einer niedrigintensiven Chemotherapie zur Behandlung von neu diagnostizierten Patienten mit Philadelphia-Chromosom-positiver (Ph+) akuter lymphoblastischer Leukämie (ALL) erhalten hat.
Dieser Meilenstein folgt auf frühere BTDs, die im März 2021 für die chronische Phase der chronischen myeloischen Leukämie und im Juni 2023 für die Behandlung von SDH-defizienten gastrointestinalen Stromatumoren vergeben wurden. Der BTD-Status priorisiert die Entwicklungs- und Prüfprozesse, was potenziell eine Prioritätsprüfung und bedingte Genehmigungen ermöglichen kann.
Ph+ ALL macht 20-30% der erwachsenen ALL-Fälle in China aus, mit einer Inzidenzrate von 0,69/100.000. Olverembatinib, der erste in China zugelassene BCR-ABL-Inhibitor der dritten Generation, ist derzeit in Chinas nationaler Liste der erstattungsfähigen Medikamente für bestehende Indikationen aufgeführt. Eine globale Phase-III-Studie, die olverembatinib plus Chemotherapie mit Imatinib plus Chemotherapie bei naïven Ph+ ALL-Patienten vergleicht, wurde im Juli 2023 genehmigt.
- Received third Breakthrough Therapy Designation in China
- Potential to be first TKI approved for first-line Ph+ ALL treatment in China
- Drug already included in China's National Reimbursement Drug List
- Addresses significant market with Ph+ ALL affecting 20-30% of adult ALL cases
- Drug not yet approved outside China
- Phase III trials still ongoing with no efficacy data reported
Insights
The Breakthrough Therapy Designation (BTD) for olverembatinib in Ph+ ALL represents a significant regulatory milestone for Ascentage Pharma, with material commercial implications. This marks the third BTD for this asset, demonstrating consistent regulatory recognition and potentially accelerating the approval timeline in China.
The designation addresses a critical unmet need in Ph+ ALL - a disease with poor prognosis where current treatments yield 5-year survival rates below 20% with chemotherapy alone. Most importantly, olverembatinib could become the first TKI approved for first-line Ph+ ALL treatment in China, establishing a valuable first-mover advantage.
From a commercial perspective, this represents a capital-efficient growth strategy as olverembatinib is already approved and commercialized in China for CML indications through the company's partnership with Innovent Biologics. The drug's inclusion in China's National Reimbursement Drug List for current indications suggests a potential reimbursement pathway, though this would require separate negotiation after approval.
The company has already received clearance for its global registrational Phase III study comparing olverembatinib plus chemotherapy to imatinib plus chemotherapy, indicating progression toward potential approval. Given the established commercial infrastructure and the specific unmet need in Ph+ ALL, this regulatory advancement represents a meaningful step in expanding the market potential of Ascentage's lead asset.
This BTD designation for olverembatinib in Ph+ ALL addresses a significant therapeutic challenge. Ph+ ALL represents 20-30% of adult ALL cases and is particularly common in elderly patients with treatment tolerance. The Philadelphia chromosome creates the BCR-ABL fusion protein that drives leukemic cell proliferation, similar to CML but with more aggressive disease progression.
As a third-generation BCR-ABL inhibitor, olverembatinib offers potential advantages over first and second-generation TKIs that have shown limitations in Ph+ ALL, including high relapse rates and poor durability of response. The drug's known ability to overcome resistance mutations, particularly the T315I mutation, could be especially valuable in this patient population where resistance development remains a significant challenge.
The specific designation for combination with low-intensity chemotherapy is clinically important, as Ph+ ALL patients often have tolerance for intensive chemotherapy regimens. This approach may allow for effective disease control while minimizing treatment-related toxicity.
The advancement to a Phase III trial against imatinib (the standard first-generation TKI) suggests confidence in potentially superior efficacy. If successful, olverembatinib could establish a new treatment paradigm for newly diagnosed Ph+ ALL patients in China, where no TKI has yet been approved for first-line treatment. The BTD status will provide accelerated regulatory review and enhanced communication with authorities, potentially bringing this treatment option to patients more quickly.
ROCKVILLE, Md. and SUZHOU, China, March 05, 2025 (GLOBE NEWSWIRE) -- Ascentage Pharma (NASDAQ: AAPG; HKEX: 6855), a global biopharmaceutical company engaged in discovering, developing, and commercializing therapies to address global unmet medical needs primarily for hematological malignancies, today announced that its drug, olverembatinib, has been granted a Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA), for combination with low-intensity chemotherapy for the first-line treatment of newly-diagnosed patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).
This marks the third BTD granted to olverembatinib in China, with the first BTD granted in March 2021, for the treatment of patients with chronic-phase chronic myeloid leukemia (CML-CP) resistant and/or intolerant to first- and second-generation tyrosine kinase inhibitors (TKIs); and the second BTD granted in June 2023, for the treatment of patients with succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) who had received first-line treatment.
BTDs are commonly granted to innovative drugs or modified novel drugs that are intended for the prevention or treatment of serious life-threatening diseases and/or conditions that severely impact the quality of life for which there is no existing treatment or where sufficient evidence indicates advantages over currently available treatment options. Drugs that have been granted BTDs are prioritized by the CDE in communications, and in receiving guidance to advance the drug development progress. Furthermore, if the applicant meets the relevant conditions after evaluation, BTD-designated drugs will be eligible for Priority Review status and conditional approvals upon submission of China’s version of a New Drug Application (NDA). In conclusion, granting of BTDs effectively accelerates development and review of innovative drugs and modified novel drugs presenting significant clinical value or addressing urgent unmet clinical needs.
The incidence rate of ALL in China is approximately 0.69/100,000; and Ph+ ALL, accounting for
Ascentage Pharma’s approved drug, olverembatinib, is the first China-approved third-generation BCR-ABL inhibitor and it is being jointly commercialized in China by Ascentage Pharma and Innovent Biologics. To date, olverembatinib has been approved in China for the treatment of adult patients with TKI-resistant CML-CP or accelerated-phase CML (CML-AP) harboring the T315I mutation and adult patients with CML-CP resistant to and/or intolerant of first- and second-generation TKIs. All approved indications have been included into the China National Reimbursement Drug List (NRDL).
In July 2023, the CDE cleared a global registrational Phase III study of olverembatinib in combination with chemotherapy versus imatinib in combination with chemotherapy for the treatment of patients with naïve Ph+ ALL, paving the way for olverembatinib to potentially become the first TKI approved in China for the treatment of Ph+ ALL in the first-line setting.
Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, “We are much encouraged to have olverembatinib’s clinical value once again recognized by the regulatory authority in China. This BTD underscores the therapeutic potential and utility of olverembatinib in Ph+ ALL, a hematologic malignancy with dismal prognosis. Moving forward, we will strive to accelerate this clinical development program for olverembatinib and bring it to more patients as quickly as possible.”
References
- Theresa Liu-Dumlao, Hagop Kantarjian, et al. Philadelphia-positive acute lymphoblastic leukemia: current treatment options. Curr Oncol Rep. 2012 Oct;14(5):387-94.
- Abou Dalle I et. Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. Curr Treat Options Oncol2019 Jan 24;20(1):4.
About Ascentage Pharma
Ascentage Pharma is a global, integrated biopharmaceutical company engaged in discovering, developing and commercializing therapies to address global unmet medical needs primarily in hematological malignancies. Ascentage Pharma has been listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK since October 2019 and has also been listed on the Nasdaq Global Market under the ticker symbol “AAPG” since January 2025.
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 TKIs that target kinase mutants emergent during cancer treatment. Ascentage Pharma is also the only company in the world with active clinical programs targeting all known key apoptosis regulators. The Company has conducted more than 40 clinical trials in the US, Australia, Europe, and China, including 11 completed or ongoing US/global registrational trials on the company’s 5 key clinical-stage assets, of which 2 trials are regulated by the US FDA.
Olverembatinib, one of the company’s lead assets, is already approved in China with all of its approved indications included into the China National Reimbursement Drug List (NRDL). Olverembatinib is an investigational drug that has not been approved for any indication outside China.
Meanwhile, a New Drug Application (NDA) for another one of Ascentage Pharma’s key drug candidates, the novel Bcl-2 selective inhibitor lisaftoclax (APG-2575), has already been accepted and granted the Priority Review designation by the China CDE.
To date, Ascentage Pharma has obtained a total of 16 ODDs from the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of the company’s investigational drug candidates. 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; and research and development relationships with leading research institutions such as Dana-Farber Cancer Institute, Mayo Clinic, National Cancer Institute and the University of Michigan.
The company has built a talented team with a wealth of global experience in the discovery and development of innovative drugs and fully functional commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfil its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients.
Forward-Looking Statements
The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, Ascentage Pharma undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events, or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions and expectations or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions and expectations may alter in light of future development.
Contacts
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Ascentage Pharma
Hogan.Wan@ascentage.com
+86 512 85557777
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FAQ
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