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 olverembatinib (R&D Code: HQP1351) has been included in the latest guidelines from the National Comprehensive Cancer Network (NCCN) for the management of  Chronic Myeloid Leukemia (CML),^[1] marking a major development in global recognition for its best-in-class drug candidate, which has been approved in China for the management of tyrosine kinase inhibitor (TKI)-resistant patients with chronic- and accelerated-phase CML (CML-CP and CML-AP).

NCCN is a not-for-profit organization allying 33 chiefly NCI-designated comprehensive cancer centers across the United States. Cancer management recommendations promulgated in the NCCN guidelines are continuously updated and downloaded more than 13 million times per year by practitioners and other key stakeholders. Serving as a standard for clinical practices in oncology in the US, the NCCN Guidelines is also one of the most widely adopted clinical guidelines for the global oncology community.

The NCCN guidelines report efficacy responses to olverembatinib in Chinese Phase I and II trials,^[2] including major cytogenetic response (MCyR) rates of 79% and 47%, complete cytogenetic response (CCyR) rates of 69% and 47%, and major molecular response (MMR) rates of 56% and 45%, in patients with CML-CP and CML-AP, respectively.

Clinical trials also suggest that olverembatinib has demonstrated effects regarding safety of the compound, with its common adverse events such as thrombocytopenia, hypertriglyceridemia, and chiefly asymptomatic elevation of enzymes that include creatine phosphokinase and liver transaminase, being typically grade 1-2 and manageable.

Findings reported at the 2023 American Society of Hematology (ASH) Annual Meeting continued to demonstrate that olverembatinib is well tolerated and effective in managing heavily TKI-pretreated CML, including in patients with challenging clinical profiles such as those with the T315I mutation who would otherwise have limited therapeutic options. These studies showed that olverembatinib significantly prolonged the rigorous efficacy benchmark of event-free survival (EFS) and reduced clinical events by 60% compared to physicians’ choices of best available therapies (BATs) in China (including imatinib, dasatinib, and nilotinib)^[3]. Moreover, olverembatinib has shown encouraging clinical benefit in patients who have failed prior treatment with other targeted drugs, including the third-generation TKI ponatinib and the allosteric STAMP inhibitor asciminib.^[4]

Olverembatinib is a novel, small-molecule, orally administered, third-generation BCR-ABL1 TKI initially approved in China in November 2021 for the treatment of adult patients with TKI-resistant CML-CP or CML-AP harbouring the T315I mutation; and then in November 2023 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.

Dr. Dajun Yang, Chairman and CEO of Ascentage Pharma, remarked that, “Inclusion in the prestigious NCCN guidelines marks another major milestone for olverembatinib. This event signals important recognition of our drug candidate by the oncology community. We are most encouraged that our cutting-edge, patient-centric innovation, which has culminated in a safe and effective treatment even in relapsed, refractory, and/or difficult-to-treat cases of CML, will bring meaningful improvement to patients’ lives. Fulfilling our mission of addressing unmet clinical needs in China and around the world, we will continue to investigate olverembatinib and accelerate our clinical development programs to benefit more patients.”

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, “This recognition of olverembatinib as a potential CML treatment by the NCCN largely validates the impressive results on this drug candidate reported to date, including selection for Oral Presentation at the 2023 ASH Annual Meeting for the sixth consecutive year. Moving forward, we will expedite our clinical development programs to bring more safe and effective therapies to patients in need. These initiatives include our ongoing pivotal registrational Phase III trials of olverembatinib, including a study in patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia [NCT06051409].”