Ascentage Pharma Unveils Third-Generation TKI HQP1351 at ASH, Offering New Hope for CML Patients with TKI Resistance
From December 1 to 4, 2018, the 60th Annual Meeting of the American Society of Hematology (ASH) was held in San Diego. ASH is the world’s largest professional society dedicated to the study of blood-related diseases, with research spanning hematology, bone marrow, immunology, coagulation, and vascular disorders. The conference brought together more than 25,000 hematology professionals from around the globe, showcasing the latest advances in research and development as well as hot topics in clinical care and treatment.
This year’s ASH meeting covered the latest clinical developments in more than 60 categories of hematologic diseases. Notably, regarding the treatment of chronic myeloid leukemia (CML), China-based Ascentage Pharma presented Phase I clinical data for its third-generation novel drug, HQP1351, which is intended for patients with resistance to tyrosine kinase inhibitors (TKIs).
Ascentage Pharma is an international drug development company based in Jiangsu, China. It is a global leader in apoptosis research and possesses a proprietary protein-protein interaction (PPI) targeted drug design platform, along with more than 100 technical patents worldwide. Ascentage Pharma is dedicated to developing innovative drugs for cancer, hepatitis B, and age-related diseases. Six of its original Class 1 new drugs have entered clinical development stages in China, the United States, and Australia. In July this year, the company completed a C-round financing of RMB 1 billion.
High Unmet Need for Overcoming Drug Resistance in CML Patients
Professor Jiang Qian is the principal investigator for the development of the novel drug HQP1351. She also serves as Secretary-General of the Chinese Chronic Myeloid Leukemia (CML) Alliance and Deputy Director of the Department of Hematology at Peking University People’s Hospital and the Peking University Institute of Hematology. She has published more than 60 articles in renowned domestic and international core hematology journals.
At the conference, Professor Jiang Qian stated that the launch of generic TKIs in China has enabled many CML patients to receive TKI therapy. However, some CML patients have not received standardized treatment following diagnosis, leading to drug resistance and suboptimal efficacy, which in turn delays therapeutic progress. Therefore, addressing TKI resistance represents a significant unmet need in new drug development.
Regarding the first- and second-generation BCR-ABL inhibitors currently available on the market, Professor Jiang Qian stated that only a small subset of chronic myeloid leukemia (CML) patients can successfully discontinue treatment, while the majority require long-term continuous medication, which often leads to poor drug adherence. HQP1351, launched this time, is an original Class 1 new drug under development by Ascentage Pharma. As an oral third-generation tyrosine kinase inhibitor (TKI), it can effectively overcome the resistance limitations associated with first- and second-generation agents and demonstrates superior efficacy in CML patients with the T315I mutation as well as those with wild-type BCR-ABL.
Clinical evidence confirms a significant increase in patient drug resistance
The trial lasted for more than two years. By the end of October 2018, Phase I clinical trial data were released. Among the 100 patients with chronic myeloid leukemia (CML) enrolled in Ascentage Pharma’s study, 86 were in the chronic phase (CP) and 14 were in the accelerated phase (AP). HQP1351 was well tolerated across all dose groups, except that two out of three patients in the 60 mg dose group experienced dose-limiting toxicities (DLTs). The maximum tolerated dose (MTD) was determined to be 50 mg. No patients withdrew from the study due to treatment-related adverse events (TRAEs) during this period.
Among evaluable cases, the complete hematologic response (CHR) rate was 96% in patients with chronic phase (CP) and 85% in those with accelerated phase (AP). Among 66 evaluable CP cases, the major cytogenetic response (MCyR) rate was 67%, while the response rate reached 78% in patients harboring the T315I mutation. Furthermore, not only patients with chronic phase (CP) and accelerated phase (AP), but also those with blast phase (BP) or other diseases featuring BCR-ABL alterations can benefit from HQP1351, indicating highly promising clinical prospects.
Professor Jiang Qian stated, “The clinical responses observed with HQP1351 in our Phase I study with a larger sample size among patients with drug-refractory relapsed/refractory chronic myeloid leukemia (CML) were impressive. This also demonstrates the strength of China’s original R&D capabilities, and we look forward to further data and progress.”
At this conference, experts from multiple countries, including China, France, and Russia, shared research findings on BCR-ABL inhibitors. HQP1351, an independently developed drug in China, has garnered significant international attention due to its promising clinical trial results, despite the relatively short follow-up period, with expectations for launching global clinical studies. Currently, the clinical study of Ascentage Pharma has been included in the oral presentations at ASH.
HQP1351 is a drug independently developed in China. Professor Jiang Qian stated that if the drug is developed and launched in the country, its pricing should not be set excessively high, ensuring affordability for the general public and thereby realizing the true value of the medication. Ascenta Therapeutics has currently initiated a Phase II registration study of HQP1351 in China to further demonstrate its efficacy and safety, with the hope of accelerating its entry into clinical practice and bringing benefit to patients with chronic myeloid leukemia (CML) in China.
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