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May 16On [date], the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) announced that SHANGHAI UNICAR-THERAPY BIOMED-PHAMACEUTICAL TECHNOLOGY CO., LTD has submitted an application for a product with...Silent Interleukin 6（IL-6）Targeted CD19 Gene-Engineered Autologous T-Cell Injection with Functional ExpressionProposed inclusionBreakthrough Therapy Drug, TargetingRefractory/Relapsed Acute Lymphoblastic Leukemia。Public information shows that this is a product developed by SHANGHAI UNICAR-THERAPY BIOMED-PHAMACEUTICAL TECHNOLOGY CO., LTD.CD19-Targeted CAR-T Cells with IL-6 Knockdown Function (ssCART-19)。
Screenshot source: CDE official website
Leukemia is one of the common hematological malignancies.Acute Lymphoblastic Leukemia(ALL) accounts for approximately 15% of all leukemia cases, among whichB-cell Acute Lymphoblastic Leukemia (B-ALL) accounts for approximately 75% of ALL. Adult B-ALL patients have a poorer overall survival compared to pediatric B-ALL patients, with a high relapse rate after initial treatment; about 60% of patients will eventually progress toRecurrent or RefractoryB-cell Acute Lymphoblastic Leukemia (r/r B-ALL). The prognosis of adult r/r B-ALL patients is extremely poor, posing a serious threat to life, and there is a lack of effective treatment options in clinical practice.According to the public information from UniCAR-Therapy BioMed-Pharmaceutical Technology Co., Ltd., ssCART-19 is the fourth-generation CAR-T product developed by the company.Can simultaneously express CAR structure and IL-6 silencing elements, significantly reducing the release level of IL-6 factor, thereby further decreasing monocyte activation and the release of pro-inflammatory cytokines., to reduce the incidence of severe cytokine release syndrome (CRS) and severe immune effector cell-associated neurotoxicity syndrome (ICANS) at the preventive level, thereby enhancing the safety of CAR-T therapy.ssCART-19 cell injection had previously received CDE approval in 2020 to conduct registration clinical trials for use.Central Nervous System Leukemia (commonly known as "CNSL")The treatment has been granted orphan drug designation by the U.S. FDA. This product is now proposed by the CDE to be included in the breakthrough therapy category, targeting the indication of Acute Lymphoblastic Leukemia (ALL).
In December 2023, SHANGHAI UNICAR-THERAPY BIOMED-PHAMACEUTICAL TECHNOLOGY CO., LTD presented relevant clinical data and the latest progress of ssCART-19 in the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) in an oral presentation and poster at the American Society of Hematology (ASH) Annual Meeting.Among them, the oral report was on the results of a Phase 1/2 clinical study, with 47 cases.r/r B-ALLPatients received ssCART-19 infusion therapy, while 40 patients received cCART-19 (classic CART-19 cells, containing only the CAR structure without IL-6 expression silencing function) infusion therapy. The efficacy and safety of the two treatments were compared. The results showed,The incidence of neutropenia, thrombocytopenia, severe CRS, ICANS, etc. in the ssCART-19 group was significantly lower than that in the control group; the peak levels of IL-6, IL-2, and TNF-α cytokines were significantly lower than those in the control group, and ssCART-19 also demonstrated better safety.。In terms of efficacy, the ssCART-19 groupObjective Response Rate (ORR)Achieve91.49% (vs control group 85%); ssCART-19 GroupMedian Overall Survival (OS) Not Reached (vs Control Group)32.93 unitsMonth); ssCART-19 GroupThe progression-free survival (PFS) at 3 months was significantly higher than that in the cCART-19 group (82.3% vs 66.9%).. According to the conclusions drawn by the researchers,Clinical studies have shown that, compared with classicalCompared with CART-19 cells, ssCART-19 combined with IL-6 gene silencing function showed good performance in terms of efficacy and safety in the treatment of relapsed/refractory B-ALL patients.In addition, UniCAR-Therapy Biomed-Pharmaceutical Technology Co., Ltd. also reported the phase 1 clinical trial data of ssCART-19 in a poster presentation.A total of 12 patients received ssCART-19 reinfusion treatment. The results showed,ORR reached 83.3%, among whichThe complete response (CR) rate was 58.3%.Complete RemissionProportion with incomplete hematologic recovery (CRi)Is 25.0%`, Median Duration of Response (DOR),`Relapse-Free Survival (RFS)Both OS and PFS have not been reached. Additionally,Even patients with central infiltration did not experience any grade of ICANS toxic side effects, demonstrating good safety.
References:
[1] Official website of the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China. Retrieved Mar 16，2024, From https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d
[2]【2023 ASH Preview】SHANGHAI UNICAR-THERAPY BIOMED-PHAMACEUTICAL TECHNOLOGY CO., LTD Announces Clinical Research Results of Innovative CD19-Targeted CAR-T with IL-6 Knockdown Function! Retrieved Dec 11, 2023, From https://mp.weixin.qq.com/s/_31w20CRXaIG86BMzWsvvQ
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