▎WuXi AppTec Content Team Report

Today(November 8), the official website of China's National Medical Products Administration (NMPA) announced,Juventas SubmittedCAR-T ProductsNaciorl Injection(Former name: Heceloncell)The marketing application has been approved.For the treatment of adult relapsed or refractory B-cell acute lymphoblastic leukemia（r/r B-ALL）. It is worth mentioning that,This is also the first CAR-T product for the treatment of leukemia to be approved for marketing in China.。

Screenshot source: NMPA official website

Leukemia is one of the common hematological malignancies, with acute lymphoblastic leukemia (ALL) accounting for approximately 15% of all leukemia cases. Among these, B-cell acute lymphoblastic leukemia (B-ALL) comprises about 75% of ALL cases.Adult B-ALL patients have poorer overall survival compared to pediatric B-ALL patients.The relapse rate of adult B-ALL after initial treatment is high, with approximately 60% of patients eventually progressing to r/r B-ALL.Adult patients with r/r B-ALL have a very poor prognosis, posing a serious threat to life, and there is a lack of effective treatment options in clinical practice.

Naciorl Injection(CNCT19 Cell Injection, Inaticabtagene Autoleucel) isA CAR-T cell therapy product targeting CD19, featuring an innovative CD19 scFv (HI19a) structure. The drug has been approved for multiple clinical trials in China, targeting indications including: treatment for adult relapsed or refractoryALL、Treatment of relapsed or refractory aggressive B-cell non-Hodgkin lymphoma and treatment of relapsed or refractory B-cell type in children and adolescentsALL. Among them, the drug is aimed atRecurrent or RefractoryThe application for ALL was alsoIncluded in the NMPA Breakthrough Therapy Designation.

December 2022,Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of ChinaOfficially Accepted the Natriolone InjectionNew Drug Application for the Treatment of Adult Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia, and it has been included in the priority review, which is also the indication for this drug's approval.

Screenshot source:CDE Official Website

The Marketing Application of NaciorlsonIt is based on a single-arm, open-label, multi-center pivotal clinical study for the treatment of adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia. The study was conducted by the Hematology Hospital of the Chinese Academy of Medical Sciences (CAMS) Institute of Hematology).Professor Wang JianxiangServe as the principal investigator, conducted across 10 clinical centers in China.The primary endpoint was the overall response rate (ORR) at 3 months after infusion of naciorlucel assessed by an independent review committee (IRC)., including complete remission (CR) and complete remission with incomplete hematologic recovery (CRi). Secondary endpoints included overall response rate (ORR) within 3 months, minimal residual disease-negative rate (MRD-), duration of response (DOR), relapse-free survival (RFS), and overall survival (OS).

At the 64th American Society of Hematology (ASH) Annual Meeting held in December 2022, researchers presented this pivotal clinical study data in an oral presentation.As of September 27, 2022, 39 adult patients with r/r B-ALL had received the infusion of NKR-201.. The specific experimental data are as follows.

• The patient showed a sustained high remission rate.：Overall Response Rate (ORR) Reached 82.1%, the median duration of response (DOR) has not been reached at a median follow-up of 9.3 months;Among patients who still had remission at 3 months, it is estimated that 80% of the patients will remain in continuous remission at 1 year.; Whether or not they subsequently undergo hematopoietic stem cell transplantation, they can exhibit sustained remission and long-term survival benefits.

• Significantly Reduced Severity of CAR-T Treatment-Related Toxicity: The incidence of Grade 3 or higher cytokine release syndrome (CRS) was 10.3%; the incidence of Grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS) was 7.7%, with no unexpected adverse events related to CD19 CAR-T therapy observed.

It is worth mentioning that, in March this year, the U.S. FDA also approvedNakio Cell InjectionIND Application for the Treatment of Adult Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia (B-ALL)NakiOther clinical studies of Olensai Injection are proceeding smoothly, benefiting more patients as soon as possible.

‍References:
[1]NMPA Conditionally Approves Juventas' Naciorlcel Injection for Marketing . Retrieved Nov 8， 2023, from https://www.nmpa.gov.cn/zhuanti/cxylqx/cxypxx/20231108092415187.html

[2] Long-term Remission of Leukemia with Long-term Survival Benefits:Juventas' Key Clinical Study Data of HJL-Cell Injection Released Globally at the 2022 ASH Annual Meeting. Retrieved Dec 12, 2022. From https://mp.weixin.qq.com/s/cnaiwst51316sJN4pmwXgg
‍[3]Juventas' New Drug Application for Heceloncel Injection Accepted by the National Medical Products Administration. Retrieved Dec 14, 2022. From https://mp.weixin.qq.com/s/1vBGtbZrvffxJkEe3pqK9A
[4]Juventas' CAR-T New Drug, HJLC Injection, IND Application Approved by U.S. FDA. Retrieved Mar 14, 2023. From https://mp.weixin.qq.com/s/IZ9WyevsyrHy80dz8SItAQ