Latest News by Industry
SUZHOU, China and ROCKVILLE, Md., Sept. 21, 2022 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, announced that the results from a Phase I and Phase II study of olverembatinib (HQP1351) for the treatment of chronic myeloid leukemia (CML) have recently been published in the renowned oncology journal, the Journal of Hematology & Oncology (JHO), further demonstrating the durable efficacy and safety of olverembatinib in patients with CML.
As a journal highly regarded by global hematology and oncology communities, JHO publishes the most cutting-edge studies covering every aspect of the hematology and oncology research and is rated with an Impact Factor (IF) of 23.1681. It is the official journal of the Chinese American Hematologist and Oncologist Network (CAHON).
Results from these studies of olverembatinib were published in a paper titled "Olverembatinib (HQP1351), a well-tolerated and effective tyrosine kinase inhibitor for patients with T315I-mutated chronic myeloid leukemia: results of an open-label, multicenter phase 1/2 trial" 2. The corresponding author of this paper is Prof. Xiaojun Huang, Director of the Institute of Hematology, Peking University, Director of the Hematology Department at Peking University People's Hospital, and the principal investigator of olverembatinib in China; the first author is Prof. Qian Jiang, Deputy Director of the Hematology Department at Peking University People's Hospital, and a co-principal investigator of olverembatinib in China.
The published results are based on 165 Chinese patients with CML heavily pretreated with multiple prior lines of treatment with tyrosine kinase inhibitors (TKIs). The patients also included those harboring the T315I mutation, and were followed up for a median of about 3 years.
In patients with CML in the chronic phase (CML-CP), the cumulative 3-year incidences of major cytogenetic response (MCyR) and major molecular response (MMR) were 79% and 56%, respectively; while in those with CML in the accelerated phase (CML-AP), the cumulative 3-year incidences of MCyR and MMR were 47% and 45%, respectively. Importantly, cytogenetic and molecular responses increased over time. In terms of safety, common non-hematologic AEs mainly included hyperpigmentation and hypertriglyceridemia, and most of these AEs were of Grade 1/2. Hematologic AEs were resolved after temporary treatment suspension or supportive care. Most AEs were controllable and tolerable, and the incidence of AEs such as thrombocytopenia fell steadily as the treatment went on.
Overall, olverembatinib demonstrated favorable tolerability and durable efficacy. Besides, olverembatinib was highly active against BCR-ABL1T315I mutants and had encouraging clinical activity against compound mutations for which no treatment option is available as of now.
CML is a hematologic malignancy of leukocytes, or white blood cells. The introduction of BCR-ABL1 TKIs significantly improved the clinical practice and management of CML. However, despite the clear clinical benefits brought by the first- and second-generation TKIs, resistance to TKIs remains a major challenge in the treatment of CML. BCR-ABL1 kinase domain mutations represent a key mechanism of drug resistance to TKIs. The T315I mutation is one of the most common mutations in drug-resistant CML, occurring in about 25% of all CML cases. Because patients with T315I-mutated CML are resistant to all first- and second-generation BCR-ABL1 inhibitors, there is an urgent unmet medical need for a safe and effective third-generation BCR-ABL1 inhibitor.
Olverembatinib, a potential best-in-class asset developed by Ascentage Pharma and a drug designated a National Major New Drug Development and Manufacturing Program, is the first and only approved third-generation BCR-ABL1 inhibitor in China, effectively ending the lack of treatment options for patients with T315I-mutated CML in the country. To date, olverembatinib has been included in the Chinese Society of Clinical Oncology (CSCO) Guidelines and the China Anti-Cancer Association's (CACA) 2022 Guidelines for the Holistic Integrative Management of Cancers, for the treatment of patients with TKI-resistant CML harboring the T315I mutation. (The CACA Guidelines also recommended olverembatinib for the treatment of patients with TKI-resistant/intolerant CML who have received at least two prior treatments.)
Although another third-generation BCR-ABL1 inhibitor had been approved in other countries, substantial unmet medical needs remain in patients with drug-resistant CML because of limited accessibility and treatment-related adverse events, including cardiovascular disorders. Consequently, clinical progress with olverembatinib has garnered widespread interest from the global hemato-oncology research community in recent years. Since 2018, clinical results of olverembatinib have been selected for oral presentations at the American Society of Hematology (ASH) Annual Meetings for four consecutive years and was nominated for "Best of ASH" in 2019. To date, olverembatinib has been granted one Fast-Track designation and three Orphan Drug designations by the US Food and Drug Administration (FDA), and an Orphan designation by the European Medicines Agency (EMA) of the EU.
Prof. Xiaojun Huang, commented, "As a Chinese clinician with over 30 years of experience in hematologic research and a principal investigator of olverembatinib, I am pleased that clinical results on this innovative treatment have been published in the JHO, once again showing that olverembatinib brings a novel China-developed therapy to patients with CML around the world. I hope to see more domestically developed novel drugs that allow Chinese physicians the opportunity to lead more clinical trials. Our goal is to generate more China-based data and clinical experience and publish robust evidence-based prospective studies that can further elevate China's status in the global research community."
Prof. Qian Jiang added that, "At present, approximately 20-30% of all CML cases are TKI-resistant/intolerant, thus resulting in disease progression in many patients. Many of these patients fail to achieve desired treatment outcomes because of drug resistance or complications even after switching to a second or third TKIs. This is why TKI-resistant CML remains a major clinical challenge globally. Results published in the JHO demonstrate that olverembatinib can effectively target CML including patients with T315I mutation and has encouraging clinical activity even in patients with drug-resistant compound mutations within the BCR-ABL1 kinase domain, signifying the drug candidate's enormous potential as an effective treatment for CML."
Prof. Yifan Zhai, Chief Medical Officer of Ascentage Pharma said, "Olverembatinib is a novel drug candidate with best-in-class potential and is also a major component of Ascentage Pharma's global innovation strategy. The publication of the Phase I/II results in the JHO signals olverembatinib's therapeutic potential in drug-resistant CML as well as Ascentage Pharma's robust R&D capabilities. We hope that olverembatinib will bring an effective and safe treatment to patients with CML globally. We remain committed to our dual mission of addressing unmet clinical needs in China and around the world. We are accelerating our global clinical development programs to benefit more patients and have also launched a Global Named Patients Program in collaboration with Tanner Pharma to make olverembatinib available to the needy patients in approximately 140 countries where the drug is not commercially available."
Highlights of the results published in the Journal of Hematology & Oncology are as follows:
Olverembatinib (HQP1351), a well-tolerated and effective tyrosine kinase inhibitor for patients with T315I-mutated chronic myeloid leukemia: results of an open-label, multicenter phase 1/2 trial
Methods:
Patient characteristics:
Phase I study
Phase II study
- Safety
- Efficacy
Conclusions
*This is a study of an investigational drug that has not been approved in the US.
References
1. 2-Year Impact Factor (2021) as released by ClarivateTM
2. Jiang Q, Li Z, Qin Y, et al. Olverembatinib (HQP1351), a well-tolerated and effective tyrosine kinase inhibitor for patients with T315I-mutated chronic myeloid leukemia: results of an open-label, multicenter phase 1/2 trial. J Hematol Oncol. Aug 18 2022;15(1):113. doi:10.1186/s13045-022-01334-z
About Ascentage Pharma
Ascentage Pharma (6855.HK) is a globally focused biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B, and age-related diseases. On October 28, 2019, Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK.
Ascentage Pharma focuses on developing therapeutics that inhibit protein-protein interactions to restore apoptosis, or programmed cell death. The company has built a pipeline of nine clinical drug candidates, including novel, highly potent Bcl-2, and dual Bcl-2/Bcl-xL inhibitors, as well as candidates aimed at IAP and MDM2-p53 pathways, and next-generation tyrosine kinase inhibitors (TKIs). Ascentage Pharma is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company is conducting more than 50 Phase I/II clinical trials in the US, Australia, Europe, and China. Olverembatinib, the company's core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML), was granted Priority Review status and a Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) and is already approved for the indication. In addition, olverembatinib was also granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EU. To date, Ascentage Pharma has obtained a total of 15 ODDs, 2 FTDs, and 2 Rare Pediatric Disease (RPD) designations from the FDA and 1 ODD from the EU for four of the company's investigational drug candidates. Ascentage Pharma has been designated for multiple Major National R&D Projects, including 5 National Major New Drug Discovery and Manufacturing projects, 1 New Drug Incubator status, 4 Innovative Drug Programs, and 1 Major Project for the Prevention and Treatment of Infectious Diseases.
Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships with numerous renowned biotechnology and pharmaceutical companies and research institutes such as UNITY Biotechnology, MD Anderson Cancer Center, Mayo Clinic, Dana-Farber Cancer Institute, Merck, AstraZeneca, and Pfizer. The company has built a talented team with global experience in discovering, developing, launching, and commercializing innovative drugs and is setting up world-class 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 or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development.
View original content to download multimedia: https://www.prnewswire.com/news-releases/ascentage-pharma-announces-phase-iii-data-of-olverembatinib-hqp1351-published-in-the-journal-of-hematology--oncology-further-validating-the-drugs-best-in-class-potential-301629866.html
SOURCE Ascentage Pharma