BEIJING – China made strides in the CAR T space this month. The country approved two more candidates to enter clinical trials in December, and forerunner Nanjing Legend Biotech Co. Ltd. said its investigational CAR T therapy LCAR-B38M/JNJ-4528 co-developed with Janssen Biotech Inc. won FDA’s breakthrough therapy designation.

CASI Pharmaceuticals Inc., of Rockville, Md., said the Chinese regulators granted an IND approval to its CNCT-19 in relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL). The application was submitted by its Chinese partner Juventas Cell Therapy Ltd., of Beijing.

Juventas will start clinical development of the CD19-targeted CAR T therapy candidate by enrolling patients early next year, while CASI still holds the worldwide commercial rights to CNCT-19 and plans to manufacture the product in China at a much lower cost than imported therapies.

Three days after the IND approval for CASI’s CNCT-19, Anhui Anke Biotechnology (Group) Co. Ltd. said it also won trial approval for its CD19-targeted CAR T therapy candidate to treat B-ALL. The approval comes almost two years after the IND was submitted to the China’s National Medical Products Administration.

Before adding two more candidates to the trial race this month, China also gave IND approval to Huadao Biopharma’s CD19-targeted therapy and Novartis Pharma AG’s CTL-019 (tisagenlecleucel) in October.

CTL-019 is already marketed as Kymriah in the U.S. Last year, Novartis partnered with Cellular Biomedicine Group to manufacture CTL-019 in China to get ready for commercialization.

Another U.S.-marketed CAR T therapy making its way to the China market – known as Yescarta (axicabtagene ciloleucel) in the U.S. and EU – is Shanghai-based Fosun Kite Biotechnology Co. Ltd.’s FKC-876, which entered clinical trials in China.

Despite the fierce race, the CAR T landscape in China is largely homogenous. CD19 remains a hot target for Chinese competitors, with 13 candidates aiming at this target given approval for trials since 2018. This is compared to a total of 18 CAR T therapies granted IND approvals in China.

The forerunning candidate: LCAR-B38M/JNJ-4528

As yet, the country has not approved any CAR T therapies. The candidate that will most likely score the first approval is Legend’s LCAR-B38M, which also differs from others in the race by taking aim at B-cell maturation antigen (BCMA).

The candidate is being co-developed globally by Legend and Janssen Biotech under a 2017 deal. It is referred to as LCAR-B38M in China, or JNJ-4528 in the rest of world. Both drug products express an identical CAR protein.

This month, JNJ-4528 was granted breakthrough therapy designation for treating relapsed or refractory multiple myeloma by the FDA, followed by orphan drug designation in February and a PRIME designation from the EMA in April.

“This marks an important regulatory milestone,” Legend’s CEO Yuan Xu told BioWorld. He added that the designation will help expedite the development and review of the therapy to treat multiple myeloma, which is seen as an incurable disease.

The designation was supported by a phase Ib/II study, whose initial results were unveiled at the American Society of Hematology (ASH) annual meeting in December.

Robert Brodsky, ASH secretary and Johns Hopkins School of Medicine professor, said they were “very promising early results.” In the study, the CAR T therapy provoked a high response rate through its targeting of BCMA.

At data cutoff, reduction in tumor burden was observed for all patients evaluable for response. The overall response rate stood at 91%, with four stringent complete responses.

The safety and efficacy results from the study were also consistent with the LEGEND-2 study, which is a first-in-human phase I study conducted in China of LCAR-B38M. The China study had enrolled 74 patients with relapsed or refractory multiple myeloma.

The overall response rate (partial response or better) was 88%, and complete response was achieved by 42 patients.

And according to results updated in July this year, the overall best response continued to stand at 88%, and complete response was achieved by 14 out of 17 patients.

“Although the sample size is too small to draw firm conclusions and multiple other factors may contribute, these outcomes suggest that different lymphodepletion regimens may contribute to differences in long-term efficacy,” researchers said at the ASH presentation.

Currently, the CAR T therapy is undergoing a phase II confirmatory trial in China. Patients are being enrolled to further evaluate LCAR-B38M in patients with advanced relapsed or refractory multiple myeloma.

“[LCAR-B38M] could provide a potential meaningful therapeutic option that may achieve and maintain deep and durable responses with a generally tolerable safety profile,” study investigator Jian-Qing Mi told BioWorld.

LCAR-B38M was the first CAR T therapy candidate that China granted IND approval to, and one of the very few that is currently in the phase II stage.

Other BCMA-targeting CAR T therapies granted trial approvals in China include Carsgen Therapeutics Ltd.'s CT-053, Hrain Biotechnology Co. Ltd.'s unnamed therapy, and Nanjing Iaso Biotherapeutics Co. Ltd.’s CT-103A.

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