FDA Grants Orphan Drug Designation For CT103A in R/R Myeloma

CT103A is a BCMA-targeted genetically modified autologous T cell immunotherapy that is able to identify and eliminate malignant and normal cells expressing BCMA in R/R Myeloma.

Fully human anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy (CT103A) has received orphan drug designation (ODD) from the FDA for the treatment of relapsed and/or refractory multiple myeloma (R/R MM), according to a press release by IASO Biotherapeutics.1

CT103A is a BCMA-targeted genetically modified autologous T cell immunotherapy that is able to identify and eliminate malignant and normal cells expressing BCMA. The customizable therapy was co-created by IASO Bio and Innovent Biologics Inc.

Previous studies have indicated that patients with R/R MM who received high-dose BCMA-targeting CAR T cells may achieve better remission while having worse adverse events. Additionally, when the disease progresses once again, the re-infusion of CAR-T cells will not be effective. CT103A has been developed with the hopes of solving this problem.

"FDA approval of ODD to CT103A is of great significance to patients with multiple myeloma and represents the FDA's recognition of CT103A and the clinical data provided by IASO Bio", said Wen Wang, MD, PhD, chief executive officer and Chief Medical Officer of IASO Bio in the press release.

"Currently, our team is advancing the clinical development of CT103A to the four dimensions of strategy including frontline therapy, combination therapies, indication expansion, and ex-China development. We are looking forward to the launch of CT103A both in China and the US as soon as possible to offer living-saving treatment option to more patients."

The multi-center, single-arm study looks to evaluate CT103A as the first-line treatment in newly diagnosed high-risk multiple myeloma subjects with induction chemotherapy as bridging therapy.2

CTI103A will be infused in the patients at 1.0 x 106 CAR+ T cells/kg via an intravenous drip between 24-72 hours post getting the chemotherapy conditioning regimen.

The study which is expected to start in April 2022 enrolls 20 newly diagnosed high-risk multiple myeloma patients aged 18 to 70. Presence of measurable lesions during screenings as well as an ECOG score of 0 or 1 are required for eligibility.

Primary end points include proportion of minimal residual disease-negative subjects as well as median progression-free survival. Some secondary end points include best overall response, median survival, event-free survival, and duration of response.

Prior to enrollment in the study, an induction therapy for 3 cycles will be given to the subjects. This chemotherapy regimen of will consist of either bortezomib-lenalidomide-dexamethasone, bortezomib-cyclophosphamide-dexamethasone or bortezomib-adriamycin-dexamethasone.

To determine enrollment in the study, an evaluation will be made in regards to whether the subject is intended to have stem cell transplantation or unsuitable for autologous hematopoietic stem cell transplantation or not, after 2 cycles of chemotherapy. If the investigator believes the subject does not meet criteria, they will receive the 3rd cycle of chemotherapy while subjects that meet the inclusion criteria will be enrolled in the study.

In addition, peripheral blood mononuclear cells will be collected to manufacture CT103A. After PBMC is collected, the subject will receive another cycle of chemotherapy and once again, be evaluated.

After CTI103A infusion, subjects will be followed in the study for a minimum of 2 years, and long-term follow-up for lentiviral vector safety will be followed for up to 15 years.

Prior to obtaining orphan drug designation, CT103A was granted breakthrough therapy designation by China's National Medical Products Administration in February 2021.

REFERENCES:
1. U.S. FDA Grants Orphan Drug Designation to BCMA CAR-T Cell Therapy Co-Developed by IASO Bio and Innovent. News Release. IASO Biotherapeutics; February 13, 2022. Accessed February 14, 2022. https://bit.ly/3LC9oGi
2. A Study of Fully Human BCMA CAR-T (CT103A) in Patients With Newly Diagnosed High-risk Multiple Myeloma (FUMANBA-2). ClinicalTrials.gov. Accessed February 14, 2022. https://bit.ly/3oLStHa