Novartis Submits IND for Kymriah (CTL019), the World’s First Approved CAR-T Therapy, in China

Yesterday (August 12), the Center for Drug Evaluation (CDE) of China's National Medical Products Administration officially accepted the clinical trial application for the CAR-T therapy CTL019 (Kymriah) submitted by Novartis (Acceptance Number: JXSL1900067).

In August 2017, CTL019 received approval from the U.S. FDA for the treatment of patients aged 25 years and younger with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or has relapsed two or more times. This marked the first CAR-T therapy approved in human history, as well as the first cell therapy approved by the FDA in the United States.

In May 2018, the FDA announced the approval of CTL019 for the treatment of adult patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) who had previously received two or more lines of systemic therapy, marking the second indication approved by the FDA for CTL019.

CTL019 is an autologous T-cell immunotherapy requiring genetic modification. The treatment process begins with the extraction of T cells from the patient, followed by genetic engineering at a manufacturing center. These T cells are engineered to express a novel chimeric antigen receptor (CAR), enabling them to directly target and destroy leukemia cells bearing the CD19 antigen. Once modified, the T cells are infused back into the patient to eliminate cancerous cells.

Novartis has stated that at its facility in Morris Plains, New Jersey, CTL019 is produced using each patient’s own cells on an individual basis. To date, Novartis has established a robust integrated manufacturing and supply chain platform capable of delivering personalized therapies globally. This process involves cryopreservation of cells collected from patients (or obtained via leukapheresis), thereby enabling treating physicians and centers to flexibly administer CTL019 therapy tailored to each patient’s specific condition.

In addition to imported products, China’s independently developed CAR-T therapies have also made certain progress.

On March [day], 2018, Nanjing Legend Biotech Co., Ltd. officially received the clinical trial approval for LCAR-B38M CAR-T therapy for autologous infusion, granted by the former China Food and Drug Administration (CFDA). This marked the first approval of a CAR-T therapy clinical trial application in China.

Despite subsequent allegations of data fabrication against Legend Biotech, the company still presented the latest safety and efficacy data for its LCAR-B38M therapy at the 60th Annual Meeting of the American Society of Hematology (ASH) in late last year. Clinical study data showed that as of June 25, 2018, 57 patients with advanced multiple myeloma, with a median age of 54 years (range: 27–72 years), had received LCAR-B38M therapy. The overall response rate (ORR) was 88%; 74% (42 patients) achieved complete response (CR), 4% (2 patients) achieved very good partial response (VGPR), and 11% (6 patients) achieved partial response (PR). Flow cytometry analysis indicated that among the 42 patients who achieved CR, 39 were negative for minimal residual disease (MRD). The median time to response was one month.

Meanwhile, the median duration of response (DOR) was 16 months; for patients achieving complete response, the median DOR was 22 months. As of the data cutoff date, disease progression occurred in 18 patients (36%) who had achieved partial response or better. The median progression-free survival (PFS) for all enrolled patients was 15 months, and for those achieving complete response, the median PFS was 24 months.

Furthermore, LCAR-B38M peaks (≥1×10⁴ copies/μg genomic DNA) were detected in blood samples from the majority of patients (n=32). Four months post-treatment, LCAR-B38M CAR-T cells were undetectable in the peripheral blood of 71% of patients, while CAR-T cells remained detectable in five patients at 10 months post-treatment.

This also marks the first presentation by Legend Biotech of the LCAR-B38M study results since the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting. Additionally, another Phase 1/2 clinical trial of LCAR-B38M for the treatment of relapsed/refractory multiple myeloma (Clinical Trial No. NCT03548207) has been conducted in the United States.

To date, more than 10 companies in China have received approval for their CAR-T therapies. According to industry experts, the first domestically developed CAR-T therapy in China is expected to be approved within three years, with prices falling to an affordable range.