FDA Grants Orphan Drug Designation to CT120 Dual-Targeted CAR-T Therapy for Acute Lymphoblastic Leukemia
核心洞察
The FDA has granted orphan drug designation to CT120, a fully human CD19 (搜索)/CD22 (搜索) dual-targeted CAR-T cell therapy developed by IASO Biotherapeutics (搜索) for treating acute lymphoblastic leukemia.
In an investigator-initiated clinical study, all 4 subjects with B-cell ALL achieved complete response after CT120 treatment, with a 100% complete remission rate and no Grade 3 or higher cytokine release syndrome or neurotoxicity observed.
The orphan drug designation provides CT120 with several advantages including FDA support for clinical research, fee waivers, and seven years of marketing exclusivity upon approval.
The FDA has granted orphan drug designation to CT120, a novel fully human CD19 (搜索)/CD22 (搜索) dual-targeted chimeric antigen receptor (CAR)-T cell therapy developed by IASO Biotherapeutics (搜索) for the treatment of acute lymphoblastic leukemia (ALL). The designation is expected to accelerate the registration and launch of CT120 in the United States, providing the therapy with several preferential policies including FDA support for clinical research, fee waivers, and seven years of marketing exclusivity upon product approval.
Clinical Efficacy Demonstrates Promise
The orphan drug designation is based on proven clinical safety and efficacy data from CT120. In an investigator-initiated clinical study (Registration No: ChiCTR2000038641), all 4 subjects with B-cell ALL achieved complete response (CR) after treatment with CT120, resulting in a complete remission rate of 100%. Notably, no Grade 3 or higher cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in the study.
"CT120 is the first dual-targeted CAR-T cell therapy. The ODD granted to CT120 demonstrates the FDA's recognition and expectation of the product," said Dr. Wen (Maxwell) Wang, CEO of IASO Bio. "CT120 has obtained two IND approvals for B-NHL and B-ALL in China, and the clinical trial for the treatment of B-NHL is going well."
Innovative Dual-Target Mechanism
CT120 represents an autologous dual-target CAR-T therapy with a unique design. Its extracellular domain contains two fully human single-chain fragment variable (scFv) sequences that can specifically bind to CD19 (搜索) and CD22 (搜索), identifying tumor cells with CD19 and CD22 expressions. This dual-targeting approach reduces tumor escape caused by the loss of target antigen, a common challenge in CAR-T therapy.
The therapy's fully human design provides low immunogenicity, reduces the antibody-drug antibody (ADA) effect, and improves CAR-T cell viability. Compared to the intracellular costimulatory signal CD28, CT120's intracellular costimulatory signal 4-1BB (搜索) and CD3ζ (搜索) demonstrate lower neurotoxicity and improved viability of CAR-T cells, resulting in more durable efficacy.
Ongoing Clinical Development
A single-armed, open-label, multicenter phase 1/2 study of CT120 is currently underway for the treatment of patients with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL). The study targets enrollment of 125 patients and will assess coprimary endpoints including the incidence of dose-limiting toxicities and adverse events in phase 1, and overall response rate at day 90 during phase 2.
The study protocol involves leukapheresis to manufacture the CAR-T cells, with bridging therapy allowed between peripheral blood mononuclear cell collection and lymphodepletion. Lymphodepletion with fludarabine and cyclophosphamide is performed for 3 consecutive days followed by 1 day of rest before CT120 infusion. Patients receive either 1.0 x 10⁶, 3.0 x 10⁶, or 6.0 x 10⁶ CAR-positive T cells/kg.
Market Context and Patient Population
According to SEER data in the United States, the annual incidence of ALL is 1.8 per 100,000, with a mortality rate of 0.4 per 100,000 and a five-year survival rate of 69.9%. The number of patients with ALL in the United States in 2021 is estimated at 115,000. In China, the five-year survival rate of leukemia patients is significantly lower at 25.4%, with 12,800 new ALL cases in 2020 and a total patient population of 143,900, expected to rise to 150,300 in 2025.
"The company is advancing the development of the product in China and United States. We look forward to the launch of this innovative therapy to cure more patients," Wang stated. The orphan drug designation positions CT120 as a potentially transformative treatment option for patients with relapsed/refractory B-ALL, addressing a significant unmet medical need in this rare disease population.