On July 19, 2022 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, metabolic, autoimmune, ophthalmology and other major diseases, and Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) has accepted and granted Priority Review designation[1] (in a CDE’s public notice ended on July 18, 2022) to a New Drug Application (NDA) that will support the full approval of olverembatinib in patients with chronic-phase chronic myeloid leukemia (CML-CP) who are resistant and/or intolerant of first- and second-generation tyrosine kinase inhibitors (TKIs) (Press release, Ascentage Pharma, JUL 19, 2022, View Source [SID1234616780]). Following the conditional NDA approval in November 2021, the acceptance for the latest application marks another milestone and will potentially bring olverembatinib to benefit a broader population of patients with CML. Innovent and Ascentage are mutually committed to the commercialization of olverembatinib in the China market.
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In November 2021, the NMPA granted a conditional approval to olverembatinib for the treatment of adult patients with TKI-resistant CML-CP or CML-AP harboring the T315I mutation as confirmed by a validated diagnostic test, thus filling an urgent treatment gap that has long hindered the clinical outcome in Chinese patients with TKI-resistant CML harboring the T315I mutation.
The acceptance and Priority Review designation for this application are based on the results from an open-label, randomized, controlled, confirmatory Phase II pivotal study (study code: HQP1351CC203) which previously served as the basis for a Breakthrough Therapy designation to olverembatinib by the CDE in March 2021. The study is designed to evaluate the efficacy and safety of olverembatinib in patients with CML-CP who are resistant and/or intolerant to first- and second-generation TKIs, with the event-free survival (EFS) as its primary endpoint. A total of 144 patients were enrolled and randomized to either receive olverembatinib or the control group to receive the current best available treatment (BAT). Results show that olverembatinib significantly improved the EFS compared to the control group and has met the pre-specified superiority criteria. Detailed results from this study will be released at an upcoming academic conference.
CML is a hematologic malignancy of the white blood cells. The introduction of BCR-ABL TKIs has significantly improved the clinical practice and management of CML. However, acquired resistance to TKIs remains a major challenge in the treatment of CML. BCR-ABL tyrosine kinase mutations represent a key mechanism of acquired drug resistance and there is an urgent unmet medical need for a safe and effective treatment. Olverembatinib is a potentially global best-in-class drug that has been developed by Ascentage Pharma and supported by the National Major New Drug Discovery and Manufacturing Program in China. As the first and only third-generation BCR-ABL inhibitor approved for the treatment of drug-resistant CML in China, olverembatinib is able to effectively target a spectrum of BCR-ABL mutants, including T315I.
The leading principal investigator of olverembatinib in China, Prof. Xiaojun Huang, MD, Director of the Institute of Hematology, Peking University, Director of the Hematology Department at Peking University People’s Hospital, commented: "The approval for olverembatinib last year has brought a breakthrough therapy for patients with drug-resistant CML harboring the T315I mutation. Meanwhile, many patients who are resistant to first- and second-generation TKIs still lack effective treatment and drug resistance to TKIs and this remains a major clinical challenge in the treatment of CML. In recent years, results from multiple clinical studies have validated olverembatinib’s therapeutic efficacy in CML patients. We hope that the second Priority Review designation granted to olverembatinib will allow more patients with CML to soon benefit from this novel drug."
Dr. Hui Zhou, Senior Vice President of Innovent, stated: "We are pleased about the acceptance and Priority Review designation for the application for olverembatinib, as it will potentially allow a broader population of patients with TKI-resistant CML to benefit from this novel therapeutic. Innovent has established a robust pipeline and franchise in hematology and we are fully committed to bringing forth more ‘high-quality biopharmaceutical products that are affordable to ordinary people’ and serve the unmet medical needs from Chinese patients as early as possible."
Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, commented, "As an innovative biopharmaceutical company dedicated to addressing the unmet medical needs of patients in China and around the world, Ascentage Pharma is forging ahead with its clinical development programs to allow more patients to benefit from our innovative drugs. Having this application for olverembatinib accepted and granted the Priority Review designation by the CDE highlights the authority’s commitment to filling the treatment gap in patients with drug-resistant CML and its strong recognition of olverembatinib’s therapeutic efficacy. We will work closely with the CDE to bring this innovative therapeutic to more patients as soon as possible."
About Chronic Myeloid Leukemia
Chronic myeloid leukemia (CML) is a malignancy caused by the clonal proliferation of hematopoietic stem cell in the bone marrow. Also referred to as chronic myelocytic leukemia, CML is one of the most common subtypes of chronic leukemia, accounting for 15% of all leukemia cases in adults. According to epidemiology data, the onset of CML in Chinese patients happens at a younger age than that in the West; the median age of onset of CML in China is around 45 – 50 years old, while it is 67 years old in the west.
BCR-ABL TKIs have significantly improved the clinical management of CML. However, acquired resistance to TKIs remains a major challenge in the treatment of CML, while BCR-ABL tyrosine kinase mutations represent a key mechanism of acquired drug resistance.
About Olverembatinib
Developed by Ascentage Pharma with support from the National Major New Drug Discovery and Manufacturing Program in China, the orally active, third-generation BCR-ABL inhibitor olverembatinib is the first China-approved third-generation BCR-ABL inhibitor targeting drug-resistant CML. Olverembatinib can effectively target a spectrum of BCR-ABL mutants, including the T315I mutation.
In November 2021, olverembatinib was approved by the NMPA of China for the treatment of adult patients with TKI-resistant CML-CP or CML-AP harboring the T315I mutation as confirmed by a validated diagnostic test. In March 2021, it was granted the Breakthrough Therapy designation by the CDE for the treatment of patients with CML-CP who are resistant and/or intolerant of first- and second-generation TKIs.
In overseas, olverembatinib was cleared by the US FDA in July 2019 to directly enter a Phase Ib study. Since 2018, the clinical results of olverembatinib have been selected for oral presentations at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meetings for four consecutive years, and was nominated for "Best of ASH (Free ASH Whitepaper)" in 2019. To date, olverembatinib has been granted one Fast Track designation and three Orphan Drug designations from the US FDA for the treatment of CML, acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML); and one Orphan Designation from the European Medicines Agency (EMA) of the European Union for the treatment of CML.
In July 2021, Ascentage Pharma (6855.HK) and Innovent Biologics (1801.HK) reached the agreement regarding the joint development and commercialization of olverembatinib in China.
*Olverembatinib has not been approved for any indication in the U.S.