FDA Approves Orca Bio's Tregzi, First Regulatory T-Cell Therapy for Stem Cell Transplant

The US Food and Drug Administration on June 30 approved Tregzi, a donor-derived cell therapy from Orca Bio, for use in matched-donor hematopoietic stem cell transplantation with a myeloablative preparative regimen in adults with hematological malignancies, to rebuild the blood and immune systems and to improve survival free of chronic graft-versus-host disease (GVHD), according to the FDA's announcement. The agency described it as the first regulatory T (Treg) cell-based immunotherapy for improving chronic GVHD-free survival in this setting.

Chronic GVHD occurs when transplanted donor cells attack the patient's body. Tregzi, known in clinical trials as Orca-T, is manufactured for each patient from the mobilized blood of an 8/8 HLA-matched related or unrelated donor. It combines three components: purified hematopoietic stem and progenitor cells to rebuild the immune system, regulatory T cells intended to suppress GVHD, and conventional T cells meant to speed immune recovery and fight the cancer.

"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," said Karim Mikhail, acting director of the FDA's Center for Biologics Evaluation and Research.

The Precision-T trial

The approval rests on Precision-T (NCT05316701), a randomized, open-label, multicenter Phase 3 trial that enrolled 187 adults with acute myeloid leukemia, acute lymphoblastic leukemia, high-risk myelodysplastic syndrome or mixed-phenotype acute leukemia at 19 US centers. Patients received Tregzi with single-agent tacrolimus or a conventional allogeneic transplant with tacrolimus and methotrexate.

At one year, 78% of patients on Tregzi had achieved chronic GVHD-free survival, the primary endpoint, compared with 38.4% of those who received a standard transplant, the FDA said. Accounting for death as a competing risk, 12.6% of Tregzi patients developed serious chronic GVHD within a year, against 44% in the comparison arm.

In its announcement, Orca Bio reported one-year overall survival of 94% with Tregzi versus 83% with conventional transplant, and non-relapse mortality of 3% versus 13%. The company said results were published in the journal Blood in December 2025.

Safety and designations

The FDA said side effects were generally consistent with those expected in stem cell transplant patients, most commonly infections, and that no patient had a severe infusion reaction and no graft failure was observed during the study period. The prescribing information includes warnings for graft failure, acute and chronic GVHD including fatal cases, infusion reactions, secondary malignancies and transmission of infectious agents, according to Orca Bio.

The application had orphan drug and regenerative medicine advanced therapy designations. The FDA granted the approval to Orca Biosystems, Inc. Tregzi is the first approved therapy for the privately held company, which is based in Menlo Park, California.