China's First and Only Approved Third-Generation BCR-ABL Inhibitor Olverembatinib Included into the 2022 National Reimbursement Drug List

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Jan 18, 2023, 22:45 ET

SUZHOU, China, and ROCKVILLE, MD, Jan. 18, 2023 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, and Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), today announced that the novel drug olverembatinib has been included into the China 2022 National Reimbursement Drug List（NRDL), for the treatment of T315I-mutant chronic-phase chronic myeloid leukemia (CML-CP) and accelerated-phase CML (CML-AP). The new version of the NRDL will take effect on Mar 1^st, 2023.

Developed by Ascentage Pharma with support from the National Major New Drug Discovery and Manufacturing program, olverembatinib is the first and only approved third-generation BCR-ABL inhibitor in China. It is, also the only approved therapy for CML harboring the T315I mutation, with clear global best-in-class potential. Olverembatinib was approved in China in November 2021 and is being jointly commercialized in China by Ascentage Pharma and Innovent. At present, clinical studies of olverembatinib are being conducted in the US to fast track the drug's journey to market in the country and allow more patients from around the world to benefit from it.

This inclusion into the NRDL in China is another milestone validating olverembatinib as an effective and safe innovative therapy addressing an urgent unmet medical need. The inclusion will bolster the accessibility of olverembatinib, allowing more patients with CML to easily and affordably access a novel therapeutic that can help to extend patients' lives and enable them to live a more fulfilling life with their families and communities.

CML is a malignancy caused by the clonal proliferation of hematopoietic stem cell in the bone marrow. It is one of the most common subtypes of chronic leukemia, accounting for 15% of all leukemia cases in adults^1-2. According to epidemiology data, the median age of onset of CML in Chinese patients is 45-50 years old, about 20 years younger than that of the Western patients³, which are among the prime years for many who have families to support.

The introduction of BCR-ABL-targeted TKIs has brought marked improvement to the clinical treatment of CML in recent years, allowing treatment-compliant patients to achieve long-term survival and the ability to live a normal and productive live. However, acquired resistance to TKIs remains a major challenge in the treatment of CML, and many patients resistant to both first- and second-generation BCR-ABL inhibitors due to their T315I mutations have long lacked an effective alternative treatment. As the first and only approved third-generation BCR-ABL inhibitor in China and the only therapy for CML harboring the T315I mutation, olverembatinib fulfills the treatment gap in T315I-mutant CML and opens the era of precision medicine for the treatment of CML in China.

In July 2022, the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) accepted and granted Priority Review designation to a New Drug Application (NDA) that will support the full approval of olverembatinib in patients with CML-CP who are resistant and/or intolerant of first- and second-generation TKIs. The potential approval of this NDA could allow olverembatinib to benefit a broader population of patients with CML in China.

"Approval by the National Healthcare Security Administration for inclusion in the NRDL will help both patients as well as China's Healthcare System," said Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma. "The NRDL inclusion will drastically improve the accessibility of olverembatinib, allowing many more Chinese patients to affordably access a novel therapy that can help restore normalcy to their lives. Remaining steadfastly committed to our mission of addressing unmet clinical needs in China and around the world for the benefit of more patients, we will continue to explore olverembatinib's efficacy and safety in other indications with the hope of benefiting more patients."

Dr. Michael Yu, Founder, Chairman and CEO of Innovent, stated: "We are glad that olverembatinib is successfully included in the NRDL, which will further alleviate the financial burden for CML patients. Innovent has always been devoted to the national health care reform, and working toward improving drug accessibility and affordability to patients. Innovent has established a well-diversified novel pipeline and a professional commercial team in hematology area, and we will proactively support the work of the government departments for the implementation of medical insurance policies to let olverembatinib benefits more Chinese patients and their families as soon as possible."

About Olverembatinib

Developed by Ascentage Pharma with support from the National Major New Drug Discovery and Manufacturing Program in China, the third-generation BCR-ABL inhibitor olverembatinib is the first and only China-approved third-generation BCR-ABL inhibitor. Olverembatinib has been granted Priority Review and Breakthrough Therapy designations by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA).

On November 25, 2021, olverembatinib was approved in China for the treatment of adult patients with tyrosine kinase inhibitor (TKI)-resistant chronic-phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation as confirmed by a validated diagnostic test. This effectively filled a long-time treatment gap in Chinese patients with TKI-resistant CML harboring the T315I mutation, thus creating enormous value for patients and the society as a whole.

As a China-developed novel drug with global best-in-class potential, olverembatinib has received widespread interest from the global hematology community. The clinical results of olverembatinib have been selected for oral presentations at the American Society of Hematology (ASH) Annual Meetings for five consecutive years, and was nominated for "Best of ASH" in 2019. In 2022, results from multiple clinical studies of olverembatinib were selected for 3 Oral Presentations at the 64^th ASH Annual Meeting^4-9.

In addition, data presented at the 64^th ASH Annual Meeting showed that olverembatinib monotherapy was efficacious and well tolerated in patients with TKI-refractory Ph+ ALL⁵. Furthermore, results from a preclinical study of olverembatinib was published in the renowned scientific journal EMBO Molecular Medicine, showing olverembatinib's therapeutic potential for the treatment of COVID-19 infections¹⁰.

To date, olverembatinib has been granted 4 Orphan Drug Designations and 1 Fast Track Designation by the US Food and Drug Administration (FDA), and 1 Orphan Designation by the European Medicines Agency (EMA) of the European Union.

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.

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 only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company is conducting more than 50 Phase I/II clinical trials 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, has been granted Priority Review designations and a Breakthrough Therapy designation by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). Furthermore, it 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 MD Anderson Cancer Center, Mayo Clinic, Dana-Farber Cancer Institute, MSD, and AstraZeneca, Pfizer and UNITY Biotechnology. 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.

About Innovent

Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines for the treatment of cancer, autoimmune disease, metabolic disorder and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 01801.HK.

Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 36 valuable assets in the fields of cancer, metabolic disorder, autoimmune disease and other major therapeutic areas, with 8 approved products on the market. These include: TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection), HALPRYZA® (rituximab biosimilar injection) , Pemazyre® (pemigatinib oral inhibitor), olverembatinib (BCR-ABL TKI) , Cyramza® (ramucirumab) and Retsevmo® (selpercatinib). An additional 3 assets are under NMPA NDA review, 5 assets are in Phase 3 or pivotal clinical trials, and 20 more molecules are in clinical studies.

Innovent has built an international team with advanced talent in high-end biological drug development and commercialization, including many global experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Sanofi, Adimab, Incyte, MD Anderson Cancer Center and other international partners. Innovent strives to work with many collaborators to help advance China's biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives. For more information, please visit: www.innoventbio.com. and www.linkedin.com/company/innovent-biologics/.

Ascentage Pharma's Forward-Looking Statement

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.

Innovent Biologics Forward-looking statement

This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. The Company does not intend to update these forward-looking statements regularly.

These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of the Company with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond the Company's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, the Company's competitive environment and political, economic, legal and social conditions.

The Company, the Directors and the employees of the Company assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialise or turn out to be incorrect.

References

1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Chronic Myelogenous Leukemia, V.2.2008[DB/OL]. NCCN Web Site. 8-28-2007.[2007-10-25]

2. HehlmannR, HochhausA, BaccaraniM, et al. Chronic myeloid leukaemia[J]. Lancet, 2007, 370（9584）: 342-350.

3. The guidelines for diagnosis and treatment of chronic myelogenous leukemia in China (2020 edition). Zhonghua Xue Ye Xue Za Zhi. 2020 May; 41(5): 353–364.

4. Jabbour E, Koller PB, Oehler VG, et al. Olverembatinib (HQP1351) Overcomes Ponatinib Resistance in Patients with Heavily Pretreated/Refractory Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL). Blood 2022;140 (Supplement_1):200-202. https://doi.org/10.1182/blood-2022-162387

5. Jabbour E, Koller PB, Oehler VG, et al. Olverembatinib (HQP1351) overcomes ponatinib resistance in patients with heavily pretreated/refractory chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Oral presentation 82.

6. Jiang Q, Li Z, Hou Y, et al. Updated Results of Pivotal Phase 2 Trials of Olverembatinib (HQP1351) in Patients (Pts) with Tyrosine Kinase Inhibitor (TKI)-Resistant Chronic- and Accelerated-Phase Chronic Myeloid Leukemia (CML-CP and CML-AP) with T315I Mutation. Blood 2022;140 (Supplement_1):203-204. https://doi.org/10.1182/blood-2022-170698

7. Jiang Q, Li Z, Hou Y, et al. Updated results of pivotal phase 2 trials of olverembatinib (HQP1351) in patients (Pts) with tyrosine kinase inhibitor (TKI)-resistant chronic- and accelerated-phase chronic myeloid leukemia (CML-CP and CML-AP) with T315I mutation. Oral presentation 83.

8. Jiang Q, Li Z, Qin Y, et al. A Five-Year Follow-up on Safety and Efficacy of Olverembatinib (HQP1351), a Novel Third-Generation BCR-ABL Tyrosine Kinase Inhibitor (TKI), in Patients with TKI-Resistant Chronic Myeloid Leukemia (CML) in China. Blood 2022;140 (Supplement_1):198-199. https://doi.org/10.1182/blood-2022-170868

9. Jiang Q, Li Z, Qin Y, et al. A five-year follow-up on safety and efficacy of olverembatinib (HQP1351), a novel third-generation BCR-ABL tyrosine kinase inhibitor (TKI), in patients with TKI-resistant chronic myeloid leukemia (CML) in China. Oral presentation 81.

10. Chan M, Holland EC, Gujral T. Olverembatinib inhibits SARS-CoV-2-Omicron variant-mediated cytokine release in human peripheral blood mononuclear cells. EMBO Mol Med. 2022 May 17;e15919.

SOURCE Ascentage Pharma