Ascentage Pharma's Olverembatinib (Olvera®), China's First Third-Generation BCR-ABL Inhibitor, Approved for T315I-Mutant CML

November 25, 2021 — Today, olverembatinib tablets (brand name: Nalikeli), an original Class 1 new drug developed by Ascentage Pharma, has officially received marketing approval from the National Medical Products Administration (NMPA) of China. It is indicated for the treatment of adult patients with chronic-phase (CP) or accelerated-phase (AP) chronic myeloid leukemia (CML) who are resistant to any tyrosine kinase inhibitor (TKI) and have been diagnosed with the T315I mutation using a fully validated testing method.

Nalikexi is a potential best-in-class novel drug developed by Ascentage Pharma, and it is supported by the National “Major New Drug Creation” Special Project. This product will be jointly commercialized in China by Ascentage Pharma and Innovent Biologics to benefit more patients and their families.As China’s first third-generation BCR-ABL targeted therapy for drug-resistant chronic myeloid leukemia (CML), the approval of Olverembatinib (Nalik) will break through the treatment bottleneck for patients with T315I mutation-mediated resistance, addressing the dilemma of having no available therapeutic options. Its approval also marks Ascentage Pharma’s formal entry into the commercialization stage.

Nayitek’s approval was primarily based on data from two pivotal Phase II registration clinical studies: the HQP1351CC201 study and the HQP1351CC202 study.Clinical data demonstrate that Nalikex exhibits favorable efficacy and tolerability in patients with chronic-phase chronic myeloid leukemia (CML-CP) and accelerated-phase CML (CML-AP) who are resistant to tyrosine kinase inhibitors (TKIs) and harbor the T315I mutation. Furthermore, response rates and depth of response continue to improve with prolonged treatment duration.

CML is a malignancy associated with white blood cells. With the market launch of TKI drugs targeting BCR-ABL, the treatment landscape for CML has been revolutionized,However, acquired resistance has remained a major challenge in the treatment of chronic myeloid leukemia (CML).Mutations in the BCR-ABL kinase domain are one of the key mechanisms of acquired resistance, with the T315I mutation being a common type of resistance mutation, occurring in approximately 25% of resistant CML cases. CML patients with the T315I mutation are resistant to all first- and second-generation BCR-ABL inhibitors currently available, thus historically facing a dilemma of having no effective treatment options.

Dr. Yang Dajun, Chairman and CEO of Ascentage PharmaHe stated, “As the company’s first commercialized product, the approval of Olverembatinib undoubtedly represents a significant milestone, marking Ascentage Pharma’s successful transition from an R&D-focused enterprise to a company with marketed products, which has greatly bolstered our confidence. We will collaborate closely with Innovent Biologics to comprehensively accelerate our commercialization strategy. Furthermore, we are actively advancing partnerships with genetic testing companies, commercial insurance providers, and online pharmaceutical platforms, aiming to make this globally leading, China-originated innovation accessible to more patients as soon as possible. We will remain steadfast in our global innovation positioning and fulfill our mission of ‘addressing unmet clinical needs of patients in China and worldwide.’ Looking ahead, Ascentage Pharma will further expand new indications for this product and advance its overseas clinical development, while continuing to accelerate the global development of our other pipeline candidates, truly realizing our vision of ‘going global from China.’”

Chronic Myeloid Leukemia (CML) is a malignant neoplasm resulting from the clonal proliferation of hematopoietic stem cells in the bone marrow. Also known as chronic granulocytic leukemia, it is the most common type of chronic leukemia, accounting for 15% of adult leukemia cases. CML patients in China tend to be younger at onset compared to those in Western countries. Epidemiological surveys indicate that the median age of onset for CML in China is 45–50 years, whereas in Western countries, it is 67 years.

With the market launch of BCR-ABL-targeted tyrosine kinase inhibitor (TKI) drugs, the treatment landscape for chronic myeloid leukemia (CML) has been revolutionized; however, acquired resistance remains a major challenge in CML management. Mutations in the BCR-ABL kinase domain represent one of the key mechanisms underlying acquired resistance, among which the T315I mutation is a common resistant variant, occurring in approximately 25% of cases with resistant CML. CML patients harboring the T315I mutation are resistant to all currently available first- and second-generation BCR-ABL inhibitors, which has historically posed a significant barrier to long-term survival in this patient population.

Nalikexi is an original Class 1 new drug developed by Ascentage Pharma. It is an oral third-generation BCR-ABL inhibitor and the first third-generation BCR-ABL targeted therapy approved in China for the treatment of resistant chronic myeloid leukemia (CML). It demonstrates outstanding efficacy against BCR-ABL and multiple BCR-ABL mutants, including the T315I mutation, and has received support from the National "Major New Drug Development" Special Project.

In October 2020, Olverembatinib was included in the Priority Review program by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) for the treatment of adult patients with chronic-phase or accelerated-phase chronic myeloid leukemia (CML) who are resistant to tyrosine kinase inhibitors (TKIs) and harbor the T315I mutation. In March 2021, this drug was designated as a Breakthrough Therapy by the CDE. Overseas, the drug received Investigational New Drug (IND) approval from the U.S. Food and Drug Administration (FDA) in July 2019, allowing it to proceed directly into Phase Ib clinical studies. In May 2020, it was granted both Orphan Drug Designation and Fast Track Designation by the U.S. FDA. In November 2021, it received Orphan Drug Designation from the European Union. Furthermore, clinical trials for this drug have been ongoing since 2018, with its findings selected for oral presentation at the American Society of Hematology (ASH) Annual Meeting for four consecutive years, including a nomination for “Best Study” at the 2019 ASH Annual Meeting.

In July 2021, Ascentage Pharma and Innovent Biologics Group (1801.HK) entered into a strategic collaboration for the joint development and co-commercialization of Olverembatinib in the Chinese market.

Ascentage Pharma is a China-based, globally oriented biopharmaceutical company dedicated to developing innovative drugs in the therapeutic areas of oncology, hepatitis B, and age-related diseases. Leveraging its robust R&D capabilities, Ascentage Pharma has established a global intellectual property portfolio and forged worldwide collaborations with leading biotechnology and pharmaceutical companies as well as academic institutions, including UNITY Biotechnology, MD Anderson Cancer Center, Mayo Clinic, Dana-Farber Cancer Institute, Merck & Co., AstraZeneca, and Pfizer. The company has built an international team with extensive experience in original drug discovery and clinical development, while simultaneously establishing high-standard commercial manufacturing and marketing teams for late-stage products. Ascentage Pharma remains committed to enhancing its R&D capabilities and accelerating the clinical development of its product pipeline, thereby fulfilling its mission to “address unmet clinical needs of patients in China and around the world” and benefiting more patients.