Asciminib Hydrochloride

SUZHOU, China and ROCKVILLE, Md., June 17, 2024 /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 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) Abstract#: P722 Presentation Type: Poster presentation Topic: Chronic myeloid leukemia – Clinical Date & Time: Friday June 14, 2024, 18:00 - 19:00 CEST Presenting Author: Dr. Elias Jabbour, Department of Leukemia, The University of Texas MD Anderson Cancer Center Highlights: Background: Existing preclinical and clinical data show that olverembatinib, an investigational, novel, potent BCR:: ABL1 TKI, has strong antitumor activity in CML or Ph+ ALL. Introduction: This multicenter, open-label study was designed to assess the safety, efficacy, and pharmacokinetic (PK) profiles of olverembatinib in patients with heavily TKI (including ponatinib and asciminib) pretreated CML or Ph+ ALL. Patient enrollment and methods: As of January 2, 2024, a total of 80 heavily TKI pretreated patients, including 62 patients with CML-CP and 18 patients with advanced Ph+ leukemia (CML-AP, CML-BP, Ph+ ALL), were enrolled. These patients were randomly assigned to receive orally administered olverembatinib at 30, 40, or 50 mg once every other day (QOD) in 28-day cycles. Efficacy results: 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. Safety results: 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. Conclusions: Olverembatinib was efficacious and well tolerated in patients with heavily TKI pretreated CML-CP and advanced Ph+ leukemias, including ponatinib- or asciminib-resistant/intolerant disease. Combination of Third Generation TKI Olverembatinib and Chemotherapy or Blinatumomab for New Diagnosed Adult Ph+ ALL Patients Abstract#: P427 Presentation Type: Poster presentation Topic: Acute lymphoblastic leukemia – Clinical Date & Time: Friday June 14, 2024, 18:00 - 19:00 CEST Presenting Author: Junjie Chen, Nanfang Hospital, Southern Medical University Highlights: Background: TKIs have improved the long-term outcomes of patients with Ph+ ALL, but resistance to TKIs remains a challenge. Previous reports showed that third-generation TKI ponatinib, combined with chemotherapy, results in a modest rate of complete molecular response (CMR) of 75% in 3 months. Our recent study, a front-line combination of olverembatinib and the PDT-ALL-2016 regimen in Ph+ ALL, had shown a promising outcome, achieving a CMR rate of 84.6% at day 90. Furthermore, the combination of TKI and blinatumomab (BITE) as a chemotherapy-free treatment approach has demonstrated safety and effectiveness. Introduction: This study explored the clinical efficacy of the front-line combination of olverembatinib and chemotherapy (TKI+chemotherapy) or olverembatinib and blinatumomab (TKI+BITE) for the treatment of Ph+ ALL. Patient enrollment and methods: From Jan 2022 to Dec 2023, 31 patients with newly diagnosed Ph+ ALL treated with olverembatinib (40mg once every other day) with pediatric-inspired chemotherapy (n=19; PDT-ALL-2016 protocol) or blinatumomab (n=12; administered for a total of 2 weeks followed by 2 weeks of break) were enrolled. The median age was 40 years old, 15 (48.4%) patients had one comorbid disease, and 8 (25.81%) patients had≥2 comorbid diseases. Efficacy results: With a median follow-up of 16 months, all patients achieved a complete remission (CR) after one cycle of treatment. For the entire cohort, 28 (90.3%) patients achieved a CMR within 3 months. Among them, 16 (84.2%) and 12 (100.0%) patients in the TKI + chemotherapy and TKI + BITE cohorts achieved a CMR within 3 months, respectively. The 1-year overall survival (OS) rate was 93.1% and event-free survival (EFS) rate was 78.4% in the entire cohort. For the TKI + chemotherapy cohort, the 1-year OS rate was 96.2% and the EFS rate was 71.5%. In the TKI + BITE cohort, the 1-year OS rate was 100.0% and the EFS rate was 90.0%. Safety results: Adverse events were observed in 10 (32.3%) patients: 3 patients (9.6%) developed septic shock during treatment, 2 patients (6.4%) experienced mild pancreatitis, 2 patients (6.4%) experienced Pneumocystis jiroveci pneumonia, 2 patients (6.4%) experienced grade 2 cytokine release syndrome (CRS), and 1 patient (3.2%) developed pulmonary embolism. Conclusions: This study showed the combination of olverembatinib and chemotherapy or blinatumomab for treating adult patients with Ph+ ALL. Among the 31 patients enrolled, a notable rate of 1-year survival and CMR was observed, which holds promise for improved long-term survival. Both the TKI + chemotherapy and TKI + BITE cohorts showed good clinical outcomes, although the TKI + BITE cohort exhibited better survival than the TKI + chemotherapy cohort. It is important to note that, although 74.19% of enrolled patients had at least one comorbid disease and the median age was 40 years, the safety profile was acceptable. Patient Reported Outcomes in Adults with TKI-Resistant Chronic Myeloid Leukemia Receiving Olverembatinib-Therapy Abstract#: P1862 Presentation Type: e-Poster presentation Topic: Chronic myeloid leukemia – Clinical Date & Time: 14, 2024, 18:00 - 19:00 CEST Presenting Author: Lu Yu, Peking University People's Hospital Highlights: Background: Third-generation (3G) TKIs have improved the outcomes of patients with TKI-resistant CML. However, there are very limited data on patient reported outcomes in adults receiving 3G TKIs such as olverembatinib. Introduction: The aim of this study was to assess health-related quality of life (HRQoL), anxiety and depression symptoms and identify variables associated with them in patients with TKI-resistant CML receiving olverembatinib-therapy. Patient enrollment and methods: 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. Survey results: 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. Conclusions: HRQoL and anxiety symptoms significantly improved over time during olverembatinib therapy in patients with TKI-resistant CML. Younger age, CP than AP, and achieving MMR on olverembatinib therapy were associated with better improvements of HRQoL. *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 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. 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. SOURCE Ascentage Pharma

The option agreement gives Ascentage a $100 million signing bonus that could be followed by milestones of up to $1.2 billion if Takeda exercises the license. With a deal worth up to $1.3 billion, Takeda could get its hands on a “potentially best-in-class” third-generation BCR-ABL tyrosine kinase inhibitor (TKI) that could rival Novartis' Scemblix. Thanks to an agreement with Ascentage Pharma, Takeda may later choose to in-license the Chinese biotech's olverembatinib, which is being developed for chronic myeloid leukemia (CML) along with “other hematological cancers,” Takeda said in a press release. If the option is exercised, Takeda can license global development and commercialization rights in all territories outside of Greater China and Russia. Ascentage, for its part, will get a signing payment of $100 million and is in line for milestones up to approximately $1.2 billion plus “double-digit royalties” on annual sales, the Chinese pharma said in an announcement. Besides, Takeda will also make a minority equity investment worth $75 million in Ascentage, a Takeda media aide told Fierce Pharma over email. While the Japanese pharma now has the option on the table, it’s not a done deal. Takeda will decide if it will exercise the licensing option based on “prespecified undisclosed development milestones,” the media aide said. The exact timing is subject to the clinical development timeline, which Ascentage is still solely responsible for now. Olverembatinib is already approved in China, where it’s the first marketed third-generation BCR-ABL1 inhibitor and the only drug cleared to treat CML patients with T315I mutations. More specifically, it’s approved for patients with TKI-resistant chronic-phase CML or accelerated-phase CML who have the T315I mutation. Outside of China, the med holds an FDA fast-track designation and an orphan drug designation from the European Medicines Agency. TKIs have already greatly impacted CML treatment ever since Novartis’ Gleevac, the first approved TKI, turned a “once fatal diagnosis into a manageable condition,” according to the Leukemia and Lymphoma society. Still, there remains an unmet need for patients whose disease is resistant or refractory to those therapies or who develop difficult-to-treat mutations stemming from the treatments, Takeda said. “Takeda has a long history of driving important treatment advances for patients, particularly those with hematological cancers facing treatment gaps,” president of Takeda’s global oncology business unit, Teresa Bitetti, noted in the release. Takeda is “highly encouraged” by the “promising results” olverembatinib has shown to date and is excited for the opportunity to potentially further develop and market the med, she added. Ascentage, meanwhile, looks to “leverage the global commercial expertise” of its partner, CEO Dajun Yang, M.D., said in the release. Olverembatinib is entering a global registrational phase 3 study coded POLARIS-2 in previously treated adult patients with chronic-phase CML with or without the T315I mutation. The trial was cleared for take-off by the FDA in February and is set to commence over the first half of this year. Novartis, too, is looking to tackle the unmet need traditional TKIs leave. The Swiss pharma's newer Scemblix has conditional FDA approval in third-line CML treatment. Now, it's looking to move into first-line treatment after beating its predecessor Gleevac with quicker and deeper molecular response rates in a head-to-head phase 3 study.