AstraZeneca's Class 1 New Drug, CDK9 Inhibitor AZD4573, Granted IND Approval in China for Relapsed/Refractory Peripheral T-Cell Lymphoma

Intelligent Finance APP learned on June 22 that according to the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration, AstraZeneca (AZN.US)’s Class 1 new drug AZD4573 has obtained clinical trial implied permission, intended for development to treat relapsed/refractory peripheral T-cell lymphoma (r/r PTCL). Public information shows that AZD4573 is a CDK9 inhibitor, currently in Phase 2 trials overseas for the treatment of hematologic malignancies.

It is reported that,PTCL accounts for approximately 7% to 10% of non-Hodgkin lymphoma (NHL).The prognosis of such patients is extremely poor, and currently, most subtypes also lack a consensus on standard treatment methods. Patients initially diagnosed with PTCL often receive comprehensive chemotherapy regimens based on anthracyclines, but the remission rate is relatively low, and the recurrence rate is high. The prognosis is even worse for patients with relapsed/refractory disease after initial treatment failure, with a five-year survival rate of less than 30%. Therefore, there is an urgent need in clinical practice to develop effective treatments for relapsed/refractory PTCL.

According to the information on AstraZeneca's official website,AZD4573 is a CDK9 inhibitor suitable for intravenous administration, designed for transient targeted binding in the human body. The transient inhibition of CDK9 by this product provides a mechanism for indirectly downregulating key cell survival proteins (such as Mcl-1) to kill tumor cells.In the biochemical assay (FRET), AZD4573 demonstrated potent inhibition of CDK9 and was selective for all other tested CDKs and kinases.

In mouse xenograft studies, AZD4573 in multiple myeloma (MM), acute myeloid leukemia (AML), and non-Hodgkin lymphoma (NHL) modelsCause lasting regression.In the in vitro and in vivo models of the above three types of tumors, the product alsoSignificantly enhance the anti-tumor activity of the BCL-2 inhibitor venetoclax, as well as enhance the activity of the covalent BTK inhibitor acalabrutinib in NHL cell lines and subcutaneous xenografts.

According to the ClinicalTrials website, AstraZeneca has registered and launched several clinical trials for AZD4573, including: a completed Phase 1 trial in subjects with relapsed or refractory hematologic malignancies; and an ongoing trial of AZD4573 in combination with acalabrutinib (a BTK inhibitor) for the treatment of patients with advanced hematologic malignancies.Phase 1/2 Study; as well as AZD4573 monotherapy or in combination with anticancer drugs for the treatment of patients with relapsed/refractory peripheral T-cell lymphoma or classical Hodgkin's lymphomaPhase 2 Study。