Fate Therapeutics’ iPSC-derived CAR-T FT819 Nabs FDA RMAT Designation for Lupus
FT819 is currently being evaluated in a multicenter phase 1 clinical trial.
Fate Therapeutics’ FT819, an investigational allogeneic induced pluripotent stem cell (iPSC)-derived chimeric antigen receptor T-cell (CAR-T) therapy, has garnered regenerative medicine advanced therapy (RMAT) designation from the FDA for active moderate to severe systemic lupus erythematosus (SLE), including lupus nephritis (LN).1
FT819, the development of which is supported by a California Institute of Regenerative Medicine grant that provides $7.9 million in funding, is currently being evaluated in a multicenter phase 1 clinical trial (NCT06308978) for the aforementioned SLE indications. Notably, patients in the study are receiving FT819 after a conditioning regimen that consists of either bendamustine alone or cyclophosphamide alone. Dose expansion in up to 10 patients is currently underway at a dose of 360 million cells and a dose of 900 million cells is being assessed in dose escalation. Initial clinical safety and activity data from the trial informed the FDA’s decision to provide the RMAT designation. Fate expends that additional data from the study will be announced at medical conferences this year.
“RMAT designation recognizes the unique therapeutic potential of our off-the-shelf CAR T-cell therapy to address the unmet need of a wide range of lupus patients,” Bob Valamehr, PhD, MBA, the president and chief executive officer of Fate Therapeutics, said in a statement.1 “We believe our current development strategy for FT819, which is designed to provide CAR T-cell therapy on-demand in a cost-effective manner and alleviate patient burden associated with intense conditioning chemotherapy and extended hospitalization, may enable treatment in the community setting and access to patients in underserved areas. With this designation, we look forward to working closely with the FDA as we seek to accelerate development of FT819 to bring this unique treatment to patients across the continuum of care.”
Data from the phase 1 trial were previously presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 7-10, 2024, in San Diego, California.2 Among 3 patients who had active LN following prior treatment with more than 1 standard of care option,“rapid, deep, and sustained” elimination of CD19+ B-cells was reported within the first month following treatment with FT819. Fate additionally noted that the first patient, who had reached at least 6 months of follow-up, maintained Definitions Of Remission In Systemic Lupus Erythematosus (DORIS) clinical remission and was not on any immunosuppressive therapies. With regard to safety, there were no dose-limiting toxicities and no cases of cytokine release syndrome, immune effector-cell associated neurotoxicity syndrome, or graft-versus-host disease reported in the 3 patients.
“We continue to be very pleased with early clinical observations of fludarabine-free conditioning and FT819 off-the-shelf, CAR T-cell therapy in patients with moderate-to-severe SLE,” Valamehr said in a December 2024 statement.2 “The remarkable experience of the first patient treated in April is ongoing, as the patient remains on-study in drug-free clinical remission. In addition, the initial clinical and translational data from the 2 additional patients treated at the first dose level continue to support the potential for disease transformation. We are now initiating dose expansion at this first dose level to accelerate development, and are also escalating dose based on the favorable safety profile observed. In addition, I am pleased to announce that the first patient has now been treated with FT819 as an add-on to maintenance therapy without conditioning chemotherapy. We believe our therapeutic approach is highly-differentiated and has the potential to transform disease outcomes without requiring patient apheresis, discontinuation of maintenance therapy, intense conditioning chemotherapy, and extended hospitalization.”
