FDA Approves Tregzi, First Regulatory T‑Cell Immunotherapy to Reduce Chronic GVHD After Donor Stem‑Cell Transplants

The U.S. Food and Drug Administration on Monday approved Tregzi, the first regulatory T cell-based immunotherapy cleared in the United States, for adult patients with blood cancers undergoing donor stem-cell transplantation. The therapy, approved for improving chronic graft-versus-host disease-free survival after allogeneic hematopoietic stem cell transplantation, targets one of transplant medicine’s most serious long-term complications.

That matters because chronic graft-versus-host disease, or cGVHD, can develop when donor immune cells attack a patient’s tissues after transplant. It is a leading cause of illness, disability, reduced quality of life and late death in transplant recipients. The approval went to Orca Biosystems Inc., whose materials had previously referred to the product by its development name, Orca-T. Tregzi is the approved product name.

The FDA described Tregzi as a donor-derived cellular immunotherapy made from the mobilized peripheral blood of an 8/8 HLA-matched related or unrelated donor. In simple terms, it is built from a matched donor’s blood cells and contains three parts: purified hematopoietic stem and progenitor cells, or blood-forming cells; regulatory T cells, or Tregs, which help suppress excessive immune responses and promote immune tolerance; and conventional T cells. Those cells are given after conditioning chemotherapy and stem-cell infusion.

The approval was based on the randomized phase 3 PRECISION-T trial, which enrolled 187 adults with hematologic malignancies, including acute leukemias and myelodysplastic syndrome. Patients were randomly assigned to receive Tregzi, previously called Orca-T, or a standard stem-cell transplant. The trial’s primary endpoint was chronic GVHD-free survival, which the FDA defined as the time from transplant to either death from any cause or the first onset of moderate or severe chronic GVHD within two years.

In the FDA’s analysis, one-year chronic GVHD-free survival was 78.0% in the Tregzi group, compared with 38.4% in the standard-transplant group. After accounting for death as a competing risk, 12.6% of patients who received Tregzi developed moderate or severe chronic GVHD within one year, versus 44% of patients who received a standard transplant. The agency said the results were “highly persuasive and internally consistent.”

On safety, the FDA said adverse events were generally consistent with what is expected in patients undergoing allogeneic stem-cell transplantation, with infections the most common. No patient had a severe infusion reaction during Tregzi infusion in the study period, and no graft failure was observed within the study period, the agency said.

The application had both Orphan Drug designation, which is meant to encourage development of treatments for rare diseases, and Regenerative Medicine Advanced Therapy designation, an FDA program intended to speed the development of promising regenerative medicines.

The approval also marks a milestone beyond transplantation. Regulatory T cells have been studied for years as a way to rein in harmful immune responses, but Treg-based therapies had remained investigational rather than licensed products in the U.S. until now.

“For patients with blood cancers who need stem cell transplantation, chronic graft-versus-host disease has long been one of the most feared and difficult-to-prevent complications,” said Karim Mikhail, acting director of the FDA’s Center for Biologics Evaluation and Research. “Today’s approval offers a genuine new approach that can help reconstitute the immune system while substantially reducing that risk and reflects the promise of what cellular therapy can deliver for patients.”