On November 8th, 2023, the National Medical Product Administration (NMPA) of China made an announcement that Inaticabtagene Autoleucel had been approved for the treatment of adults with 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 approved for the treatment of leukemia in China.
Leukemia is one of the common blood tumors. Acute lymphoblastic leukemia (ALL) accounts for about 15% of all leukemias, among which B lymphocyte-ALL (B-ALL) accounts for about 75% of ALL. Adult B-ALL patients have worse overall survival than pediatric B-ALL patients. Adult B-ALL has a high recurrence rate after initial treatment, and will eventually progress into r/r B-ALL in about 60% of patients. The prognosis of adult patients with r/r B-ALL is extremely poor and life-threatening, and there is a lack of effective clinical treatments.
Inaticabtagene Autoleucel (CNCT19 cell injection) is a CD19-targeted CAR-T cell therapy product with an innovative CD19 scFv (HI19a) structure. The innovative therapy has been approved for multiple clinical trials in China, and its indications include treatment of relapsed or refractory ALL in adults, treatment of relapsed or refractory aggressive B-cell non-Hodgkin lymphoma, and treatment of children and adolescents Relapsed or refractory B-cell ALL. Among them, this innovative medicine’s application for relapsed or refractory ALL has also been included in the breakthrough therapy category by NMPA.
In December 2022, the Center for Drug Evaluation (CDE) of NMPA officially accepted the new drug marketing application for Inaticabtagene Autoleucel for the treatment of adults with relapsed or refractory B-cell acute lymphoblastic leukemia, it was included in the priority review, this is also the indication for which Inaticabtagene Autoleucel was approved this time.
The marketing application for Inaticabtagene Autoleucel is based on a single-arm, open-label, multi-center pivotal clinical study for the treatment of adults with r/r B-ALL. The study was led by Professor Wang Jianxiang from the Hematology Hospital of the Chinese Academy of Medical Sciences (Institute of Hematology, Chinese Academy of Medical Sciences) as the principal investigator and was conducted at 10 clinical centers in China. The primary endpoint of the study was the overall response rate (ORR) at 3 months after Inaticabtagene Autoleucel as assessed by an independent review committee (IRC), including complete response (CR) and complete response (CRi) with incomplete blood cell recovery. Secondary study endpoints include overall response rate (ORR), minimal residual disease-negative rate (MRD-), duration of response (DOR), relapse-free survival (RFS) and overall survival (OS) within 3 months.
At the 64th American Hematology Annual Meeting (ASH) in December 2022, researchers released this key clinical research data in the form of an oral report at the conference. As of September 27, 2022, 39 adult patients with r/r B-ALL have received infusion of Inaticabtagene Autoleucel. The specific test data are as follows.
- The patients showed a durable and high response rate: the overall response rate (ORR) was 82.1%, and at a median follow-up of 9.3 months, the median duration of response (DOR) had not been reached; among patients who were still in response at 3 months, 1 It is estimated that 80% of patients will be in sustained remission by the year; regardless of whether they receive subsequent hematopoietic stem cell transplantation, all patients will show sustained remission and long-term survival benefits.
- Significantly reduced severity of toxicity related to CAR T-cell therapy: the incidence rate of grade 3 and above cytokine release storm (CRS) was 10.3%; the incidence rate of grade 3 and above immune effector cell-associated neurotoxic syndrome (ICANS) was 7.7%, nothing more than 10.3%. None adverse events related to CD19-targeting CAR-T therapy occurred.
It is worth mentioning that in March this year, the US FDA also approved the IND application for Inaticabtagene Autoleucel, which is intended to be developed for the treatment of adults with r/r B-ALL. We wish that other clinical studies of Inaticabtagene Autoleucel will also proceed well and benefit more patients as soon as possible.