SUZHOU, China, and ROCKVILLE, MD, June 17, 2024—Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, announced today that updated results from three studies of olverembatinib (HQP1351), the first China-approved third-generation BCR-ABL1 inhibitor, have been released in posters at the 2024 European Hematology Association Hybrid Congress (EHA 2024), taking place in Madrid, Spain.
Building on the data reported at the 2023 American Society of Hematology Annual Meeting, Ascentage Pharma has released the updated median 1-year follow-up data of olverembatinib in patients with chronic myeloid leukemia (CML) and Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). In the results, olverembatinib showed excellent durable clinical benefits and favorable long-term tolerability in patients who had been treated with multiple TKIs (including those who were resistant to ponatinib and/or asciminib), regardless of whether they harbored the T315I mutation.
Dr. Elias Jabbour, MD, Department of Leukemia, The University of Texas MD Anderson Cancer Center, and the Principal Investigator of the study, commented, “The study on olverembatinib demonstrates significant efficacy and a manageable safety profile in patients with heavily pretreated CML and Ph+ ALL, including those with resistance or intolerance to ponatinib and asciminib. These findings indicate that olverembatinib has the potential to be a valuable treatment option for this challenging patient population, warranting further investigation through long-term studies to confirm its clinical benefits.”
“Updates released at this year’s EHA Hybrid Congress, combined with previously reported data, reaffirmed the enormous potential of olverembatinib in patients who are resistant to ponatinib and asciminib,” said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. “Moving forward, we will expeditiously advance the clinical development of this global best-in-class drug in efforts to bring a new treatment option to patients as soon as possible.”
Olverembatinib is a global best-in-class drug developed by Ascentage Pharma. As the first China-approved third-generation BCR-ABL1 inhibitor, olverembatinib has been approved for two indications in China, including adult patients with tyrosine kinase inhibitor (TKI)-resistant chronic-phase CML (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. Olverembatinib is jointly commercialized in China by Ascentage Pharma and Innovent Biologics. A global registrational Phase III trial of olverembatinib in treatment-naïve patients with Ph+ ALL is currently ongoing and could potentially lead olverembatinib to become the first TKI approved in China for first-line treatment of Ph+ ALL.
The EHA Hybrid Congress is the largest gathering of the hematology field in Europe. It showcases the most cutting-edge research and state-of-the-art innovative therapies, attracting over 10,000 clinical experts and researchers from more than 100 countries every year. This year, in addition to the latest data on olverembatinib, Ascentage Pharma also released those of its Bcl-2 inhibitor lisaftoclax (APG-2575) and the EED inhibitor APG-5918.
Highlights of those data of olverembatinib presented at EHA 2024 are as follows:
Olverembatinib Overcomes Ponatinib and Asciminib Resistance in Patients (Pts) with Heavily Pretreated Chronic Myeloid Leukemia (CML) and Philadelphia-Positive Acute Lymphoblastic Leukemia (Ph+ ALL)
Highlights:
1）In patients with CML-CP:
– 31/51 (60.8%) patients achieved a complete cytogenetic response (CCyR), and 25/59 (42.4%) achieved a major molecular response (MMR). No differences in the response rates of patients with/without the T315I mutation were observed.
– In patients who failed prior treatment with ponatinib, 15/26 (57.7%) achieved a CCyR (including 10/19 [52.6%] patients with prior resistance to ponatinib and 3/4 [75.0%] with prior intolerance of ponatinib), and 11/30 (36.7%) patients achieved an MMR (including 9/21 [42.9%] patients with prior resistance to ponatinib and 1/6 [16.7%] with prior intolerance of ponatinib).
– In patients who were asciminib-resistant, 4/8 (50.0%) achieved a CCyR, and 4/12 (33.3%) achieved an MMR.
2）In patients with advanced Ph+ leukemia:
– 3/14 (21.4%) patients achieved a CCyR, and 3/17 (17.6%) patients achieved an MMR.
– 72 (90.0%) patients experienced treatment emergent adverse events (TEAEs) during their treatment with olverembatinib. Most of the TEAEs were mild to moderate in severity.
– Common grade≥3 TEAEs included thrombocytopenia (17.5%), neutropenia (12.5%), and increases in blood creatine phosphokinase (12.5%). Serious adverse events occurring in ≥3 (3.8%) patients included atrial fibrillation, COVID-19 infection, febrile neutropenia, and intestinal obstruction. No treatment-related adverse events (TRAE) led to death. Two (2.5%) patients experienced Grade 1 treatment-related arterial occlusive events, one each with angina pectoris and cardiac failure.
Combination of Third Generation TKI Olverembatinib and Chemotherapy or Blinatumomab for New Diagnosed Adult Ph+ ALL Patients
Highlights:
Patient Reported Outcomes in Adults with TKI-Resistant Chronic Myeloid Leukemia Receiving Olverembatinib-Therapy
Highlights:
– Subjects with TKI-resistance receiving olverembatinib in the multicenter study were invited to complete the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), the Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS) questionnaires at baseline and regularly during the study treatment. The time trends of the patient reported outcomes were estimated by a linear model using the generalized estimating equation based on the independent working correlation matrix. The generalized estimating equation model was utilized to assess the impact of patients’ characteristics at baseline and treatment response during olverembatinib therapy on HRQoL, SAS, and SDS.
– A total of 159 patients in CP or AP CML were included in this study. Median (range) age was 42 (20-74) years. 104 (65%) patients were male. Interval from diagnosis of CML to initiation of olverembatinib therapy was 5 (0.3-23) years. 77 (48%) patients received olverembatinib therapy within 5 years from the diagnosis of CML. All patients completed the QLQ-C30 questionnaire; and 115 completed the SAS and SDS questionnaires.
– Assessed by the EORTC QLQ-C30 questionnaire, the top 3 severe symptom burdens at baseline were financial difficulties, fatigue, and insomnia. Eight scale items including global health, physical functioning, emotional functioning, fatigue, pain, dyspnea, diarrhea and financial difficulties improved significantly during olverembatinib therapy. No scale deteriorated significantly. In multivariate analysis, age < 40 years was associated with better improvement of social functioning (p = 0.021); CP (vs. AP), better improvement of dyspnea (p = 0.028) and diarrhea (p = 0.042); achieving MMR, better improvement of global health (p = 0.005), nausea and vomiting (p = 0.009), and diarrhea (p = 0.001).
– At baseline, 96 (84%) patients were normal according to the SAS score; and 19 (16%) had mild or moderate anxiety symptoms. 64 (56%) patients were normal according to the SDS score; 37 (32%) had mild depression symptoms; and 14 (12%), moderate or severe depression symptoms. SAS score was decreased significantly during olverembatinib therapy over time (p < 0.001) while the SDS score did not change significantly. At 36 months on olverembatinib therapy, 78 (95%) and 48 (59%) patients had no anxiety and depression symptoms assessed by SAS and SDS questionnaires, respectively. There was no variable identified that impacted the change of SAS score during olverembatinib therapy.
*Olverembatinib is an investigational drug that has not been approved for any indication outside the Chinese mainland.
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 9 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 40 Phase clinical trials, including 5 global registrational phase III studies, in the US, Australia, Europe, and China. Ascentage Pharma has been designated for multiple Major National R&D Projects, including five Major New Drug Projects, one New Drug Incubator status, four Innovative Drug Programs, and one Major Project for the Prevention and Treatment of Infectious Diseases.
Olverembatinib, the company’s core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company’s first approved product in China, has been granted Priority Review Designations and Breakthrough Therapy Designations by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). To date, the drug had been included into the China 2022 National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EMA of the EU. 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 with numerous renowned biotechnology and pharmaceutical companies and research institutes such as UNITY Biotechnology, MD Anderson Cancer Center, Mayo Clinic, Dana-Farber Cancer Institute, MSD, and AstraZeneca. The company has built a talented team with global experience in the discovery and development of innovative drugs and is setting up its 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.
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