1st CAR T-Cell Therapy in China for Myeloma Now Under Review
The China National Medical Products Administration (NMPA) has agreed to review an application for Equecabtagene autoleucel — the country’s first chimeric antigen receptor (CAR) T-cell therapy — for relapsed or refractory multiple myeloma.
The CAR T-cell therapy, the first to be developed domestically in China, was awarded breakthrough therapy designation (BTD) by the NMPA in February 2021.
Equecabtagene autoleucel also was granted orphan drug designation by the U.S. Food and Drug Administration in February 2022.
Its developers, IASO Biotherapeutics and Innovent Biologics, submitted the new drug application (NDA) in China based on promising results from a multicenter Phase 1/2 study in patients with myeloma that had relapsed or was hard to treat (refractory).
“We are glad about the NDA acceptance of Equecabtagene autoleucel,” Yongjun Liu, MD, PhD, Innovent’s president, said in a press release, noting that the therapy “demonstrated impressive efficacy and favourable safety profiles” in clinical trials.
“We hope that this breakthrough therapy could be approved in the near future, and we will actively coordinate with all parties including the government authorities, hospitals, commercial insurance and charity funds to bring benefit to more multiple myeloma patients,” Liu said.
The research into Equecabtagene autoleucel — first launched in 2018 — was led by Lugui Giu, MD, and Chunrui Li, MD, PhD, the principal investigators at the trial’s two study sites. Giu oversaw the research at the Chinese Academy of Medical Science Hematology Hospital, in Beijing, while Li led the study at the Tongji Hosptial Tongji Medical College, in Shanghai.
CAR T-cell therapy uses a patient’s own immune cells to fight cancer. The therapy involves collecting the patient’s T cells — a type of immune cell — and genetically modifying them to produce a chimeric antigen receptor, or CAR, that targets a specific cancer protein. In this case, the target is the BCMA protein, found at significantly higher levels in people with multiple myeloma.
According to the scientists, this therapy has been shown to be particularly useful for patients who do not respond to available treatments.
“Although the survival in [myeloma] patients has been dramatically extended to 7-10 years on average with recent drug development, the disease is still incurable, and relapse or refractory after standard therapies is common for most [myeloma patients],” Giu and Li said in a joint statement.
Usually, the median progression-free survival of myeloma patients who receive three or more lines of therapy is three to six months, and overall survival time is less than one year, the team noted.
“The first patient of the study has maintained strict complete remission for over 40 months,” said Wen (Maxwell) Wang, MD, PhD, CEO and chief medical officer of IASO Bio.
“Equecabtagene autoleucel is China’s first domestically developed CAR T-cell therapy with global intellectual property rights and the first BCMA-targeting CAR T-cell therapy with its NDA formally accepted by the NMPA,” Wang said, adding, “This is a significant milestone for IASO Bio.”
The multicenter Phase 1/2 study enrolled 79 patients with multiple myeloma who had received at least three lines of prior therapy containing at least a proteasome inhibitor and an immunomodulatory agent. None of the patients responded to their last line of treatment.
Among them, the overall response rate (ORR) was 94.9% and the complete response/stringent complete response (CR/sCR) rate was 58.2%.
The median time to recovery was 16 days and the median time to CR/sCR was 95 days. For 13 patients who had previously received CAR-T therapy, ORR was 98.5%, with six patients achieving CR/sCR. Additionally, for 11 patients with extramedullary multiple myeloma at baseline, ORR was 100%, with nine patients achieving CR/sCR.
The most common treatment-related adverse events were low neutrophil, leukocyte, lymphocyte, and platelet counts, and anemia.
“These results suggest that Equecabtagene autoleucel is potentially a new and effective immunotherapy treatment option for patients with [myeloma]. We hope that Equecabtagene autoleucel can be launched in China soon, bringing long-term benefits to patients,” Giu and Li said.
China’s NMPA also is reviewing the use of Equecabtagene autoleucel as a treatment for neuromyelitis optica spectrum disorder, a type of autoimmune disease.