SUZHOU, China and ROCKVILLE, Md., Dec. 13, 2023 /PRNewswire/ — 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 it has released updated data from a randomized, controlled, registrational Phase II study of the company’s novel drug candidate, olverembatinib (R&D code: HQP1351), in patients with chronic-phase chronic myeloid leukemia (CML-CP) resistant and/or Intolerant to first- and second-generation tyrosine kinase inhibitors (TKIs), in an Oral Presentation at the 65th American Society of Hematology (ASH) Annual Meeting, taking place in San Diego, CA, the United States. Prof. Xiaojun Huang and Prof. Qian Jiang, from the hematology department of Peking University People’s Hospital, are the principal investigators of the study.

The ASH Annual Meeting is one of the largest gatherings of the international hematology community, bringing together the most cutting-edge scientific research and latest data of investigational therapies that represent leading scientific and clinical advances in the global hematology field. Garnering growing interest from the global research community, multiple studies of Ascentage Pharma’s key drug candidates (including olverembatinib and lisaftoclax) have been selected for presentations at this year’s ASH Annual Meeting, including two Oral Presentations on olverembatinib. This is the sixth consecutive year in which study results on olverembatinib have been selected for Oral Presentations at the ASH Annual Meeting.

Data from this Chinese study (HQP1351CC203) of olverembatinib showed that, in patients with CML-CP resistant and/or intolerant to prior treatment with TKIs, the olverembatinib arm achieved statistically significant improvement in event-free survival (EFS) compared to the control arm that was treated with the best available therapy (BAT), thus meeting the primary endpoint of the study with markedly improved prognosis for patients in the olverembatinib arm, compared to those in the control arm. In November 2023, based on results from this study, the China National Medical Products Agency (NMPA) approved olverembatinib for the treatment of adult patients with CML-CP resistant to and/or intolerant of first- and second-generation TKIs. Olverembatinib is being jointly commercialized in China by Ascentage Pharma and Innovent Biologics.

Prof. Qian Jiang, deputy director of the hematology department of Peking University People’s Hospital and a principal investigator of the study, commented, “In November 2021, olverembatinib was granted its first marketing authorization that ended the lack of effective treatment for patients with T315I mutant CML in China. However, resistance to TKIs remained a major challenge in the treatment of CML. According to existing clinical data, 30%-50% of patients treated with first- or second-generation TKIs develop resistance/intolerance. These patients have a very poor prognosis due to the lack of effective treatments. The updated data from this randomized, controlled, registrational Phase II study showed that olverembatinib significantly improved the EFS for patients with first- and second-generation TKI-resistant and/or intolerant CML while exhibiting potent efficacy and favorable safety. These results supported the recent approval for an additional indication of olverembatinib. We are confident that, through standardized diagnosis and treatment, olverembatinib will benefit the broader population of patients with CML by better treatment responses earlier and further improving the prognosis of patients with TKI-resistant and/or intolerant CML.”

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, “Results from this study supported the recent approval for an additional indication of olverembatinib and the selection for Oral Presentation at the ASH Annual Meeting for the sixth consecutive year, which are encouraging achievements that indicated strong recognition for our work. Remaining committed to the mission of the addressing unmet clinical needs in China and around the world, we will expedite our clinical development programs to bring more safe and effective therapies to patients in need.”

Highlights of the study presented at ASH 2023:

Olverembatinib (HQP1351) Demonstrates Efficacy Versus. Best Available Therapy (BAT) in Patients with Tyrosine Kinase Inhibitor-Resistant Chronic Myeloid Leukemia Chronic-Phase in a Registrational Randomized Phase 2 Study

Format: Oral Report

Abstract: #869

Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Novel Therapeutic Approaches

Time: December 11, 2023, Monday; 3:45 PM (Pacific Time) / December 12, 2023, Tuesday; 7:45 AM (Beijing Time)

Highlights:

Background: Patients with CML resistant and/or intolerant to first- and second-generation TKIs have a high risk of disease progression and poor prognosis. Results from a Phase I study and a registrational Phase II study of olverembatinib (HQP1351-SJ0002, HQP1351CC201/202) have demonstrated favorable safety, potent antitumor activity, as well as potent inhibitory activity against BCR-ABL1WT and T315I mutations. Moreover, olverembatinib also showed significant inhibitory activity against BCR-ABL1 compound mutations.

Methods: The study enrolled patients with CML-CP resistant and/or intolerant to 3 TKIs, including imatinib, dasatinib, and nilotinib, with an ≤ 2 Eastern Cooperative Oncology Group (ECOG) performance score and adequate organ functions. Patients were randomized at a 2:1 ratio to receive olverembatinib (40mg, every other day [QOD]) or BAT (interferon, hydroxyurea, homoharringtonine [HHT], and TKIs [imatinib, dasatinib, and nilotinib] in monotherapy or combinations). The primary endpoint of this study was EFS. After reaching EFS, patients in the BAT arm were allowed to cross-over to the olverembatinib arm for continued treatment.

Patients: As of October 17, 2023, a total of 144 patients were enrolled, of whom 96 patients received olverembatinib and 48 received BAT. In the BAT arm, 22 (47.8%) patients received nilotinib; 16 (34.8%) received dasatinib; 2 (4.3%) received imatinib; 2 (4.3%) received nilotinib combined with hydroxyurea; 2 (4.3%) received dasatinib combined with interferon; 1 (2.2%) received nilotinib combined with interferon; and 1 (2.2%) received interferon combined with hydroxyurea and HHT. The median (range) duration of treatment of the olverembatinib arm and the BAT arm were 21.4 (0.6-44.2) months and 2.9 (0.2-40.5) months, respectively. The median (range) duration of follow-up of the two arms were 30.8 (1.3-46.0) months and 30.4 (0-45.8) months, respectively.

Efficacy results:

  • Clinical data from this study showed, in patients with CML-CP resistant and/or intolerant to prior treatment with TKIs, the olverembatinib arm achieved statistically significant improvement in EFS compared to the BAT arm, thus reaching the primary endpoint. Compared with the BAT control arm, olverembatinib reduced event risk by 60%. The EFS of the olverembatinib arm at 12, 24, and 36 months were 59% (95% CI, 48-68), 47% (95% CI, 36-57), and 47% (95% CI, 36-57), respectively. Among the 48 patients in the BAT arm, 35 (73%) patients were crossed-over to received olverembatinib after reaching the primary endpoint (25/35 patients were crossed-over 3 months prior to this study).
  • The olverembatinib arm showed a significantly higher cumulative response rate than the BAT arm, as well as durable efficacy.

Safety results: In the olverembatinib arm, the median duration of treatment was 21.4 (0.6-44.2) months, and 85.4% of patients experienced grade ≥3 adverse events (AEs). In the BAT control arm, the median duration of treatment was 2.9 (0.2-40.5) months, and 67.4% of patients experienced grade ≥3 AEs. The incidence of grade ≥3 hematologic AEs in the olverembatinib arm declined over time as the treatment went on, and the incidence of grade ≥3 non-hematologic AEs did not increase as the treatment continued. As of October 17, 2023, a total of 98 patients (56 [58.3%] patients in the olverembatinib arm and 42 [87.5%] patients in the BAT control arm) discontinued therapies due to disease progression/treatment failure (13.5% vs 45.8%), AEs (28% vs 31.3%), consent withdrawal (9.4% vs 2.1%), poor compliance (3.1% vs 2.1%), death (1% vs 2.1%), drop-out from follow-up (0%-2.1%), and other reasons (3.1% vs 2.1%).

Conclusions: In patients with TKI-resistant and/or intolerant CML, the olverembatinib arm has achieved significantly improvement in EFS (HR=0.4, 95%CI 0.3,0.5), p<0.001, comparted with the BAT control arm, thus reaching the primary endpoint of the study. In addition, the olverembatinib arm has shown a higher cumulative response rate and longer duration of responses.

* 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 I/II clinical trials 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, 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, 2 FTDs, and 2 Rare Pediatric Disease (RPD) Designations 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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