New Indication of Olverembatinib Included into China 2024 NRDL

Olverembatinib is a novel drug developed by Ascentage Pharma with support from the National Major New Drug Development Program in China and the first third-generation BCR-ABL inhibitor approved by the China National Medical Products Administration (NMPA). As a novel drug, olverembatinib can effectively target BCR-ABL and a spectrum of BCR-ABL mutants, including the T315I mutation. In November 2021, olverembatinib received its first approval in China, thus became the first therapy approved for the treatment of T315I mutant CML in the country. In November 2023, olverembatinib was approved for the treatment of adult patients with CML-CP resistant and/or intolerant of first-and second-generation TKIs. Olverembatinib is being jointly commercialized in China by Ascentage Pharma and Innovent Biologics.

CML is a hematologic malignancy of the white blood cells. The introduction of BCR-ABL TKIs have significantly improved the management of CML. However, TKI resistance is still a global challenge for CML treatment. 20%-40% of patients fail to achieve desired treatment outcome due to resistance or intolerance to TKIs ^1-3 , thus leading to disease progression or even death. The successful renewal and the inclusion of additional indication of olverembatinib in the NRDL is expected to greatly improve the drug’s accessibility, bringing benefit to more and a broader population of patients with CML in China.

References

1. O’Brien SG, Guilhot F, Larson R, et al. Imatinib      compared with interferon and low-dose cytarabine for newly diagnosed      chronic-phase chronic myeloid leukemia. Engl J Med. 2003 Mar 13;348(11):994-1004.

2. Jabbour      E, Kantarjian H. Chronic myeloid leukemia: 2014 update on diagnosis,      monitoring, and management. Am J Hematol. 2014 May;89(5):547-56.

3. Larson      R, Hochhaus A, Hughes T, et al. Nilotinib vs imatinib in patients with      newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia      in chronic phase: ENESTnd 3-year follow-up. Leukemia. 2012      Oct;26(10):2197-203.

* Olverembatinib is an investigational drug that has not been approved for any indication outside China.

Developed by Ascentage Pharma, the novel drug olverembatinib is an orally-available third-generation tyrosine kinase inhibitor (TKI), and the first China-approved third-generation BCR-ABL inhibitor that can effectively target BCR-ABL and a spectrum of BCR-ABL mutants, including the T315I mutation. Olverembatinib, developed with support from the National Major New Drug Development Program in China, has also been granted Priority Review designations and Breakthrough Therapy designations by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA).

At present, olverembatinib has been approved in China for the treatment of adult patients with TKI-resistant chronic-phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation; and adult patients with CML-CP resistant and/or intolerant of first-and second-generation TKIs.

In addition to CML, olverembatinib has also shown potential clinical benefits to patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). A global registrational Phase III study of olverembatinib in newly diagnosed patients with Ph+ ALL is currently underway, potentially paving the way for olverembatinib become the first China-approved TKI for the treatment of patients with Ph+ ALL in the first-line setting. In the area of solid tumors, olverembatinib is being evaluated in a global registrational Phase III study for the treatment of succinate dehydrogenase- (SDH-) deficient gastrointestinal stromal tumor (GIST) and has already been granted a Breakthrough Therapy designation by the China CDE.

As a novel drug, 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 seven consecutive years. To date, olverembatinib has been granted four Orphan Drug Designations and a Fast Track Designation by the US Food and Drug Administration (FDA), and an Orphan Designation by the EMA of the EU. In February 2024, olverembatinib was cleared by the US FDA to enter a global registrational Phase III study.

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.

In June 2024, Ascentage Pharma and Takeda, a multinational pharmaceutical company, entered into an Exclusive Option Agreement for olverembatinib. If exercised, the Option would allow Takeda to license global rights to develop and commercialize olverembatinib in all territories outside of, among others, China

Ascentage Pharma (6855.HK) is a global, integrated biopharmaceutical company engaged in discovering, developing and commercializing therapies to address global unmet medical needs primarily in malignancies. 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.

The company has built a rich pipeline of innovative drug candidates that includes 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 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 has conducted more than 40 clinical trials in the US, Australia, Europe, and China, including 13 registrational studies (completed/ ongoing/planned).

Olverembatinib, the company’s first lead asset developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company’s first approved product in China, has been granted Priority Review Designations and Breakthrough Therapy Designations by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). To date, the drug had been included into the China National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted Orphan Drug Designations (ODDs) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EMA of the EU.