FDA Approves Tregzi for Matched Donor HSCT in Hematologic Malignancies

The FDA approved allogeneic regulatory T cell-based immunotherapy with hematopoietic stem and progenitor cell (HSPC) and T cells-vldq (Tregzi; Orca Bio) on June 30, 2026, for use in matched donor hematopoietic stem cell transplantation (HSCT) with a myeloablative preparative regimen, for hematopoietic and immunologic reconstitution, and to improve chronic graft-versus-host disease (cGVHD)-free survival in adults with hematological malignancies.¹

Tregzi received regenerative medicine advanced therapy (RMAT) and orphan drug designations from the FDA for the prevention of GVHD or death in patients eligible for HSCT. The approval marks the first allogeneic regulatory T cell-based immunotherapy to receive FDA authorization, offering transplant physicians a precision-engineered cell therapy alternative to conventional alloHSCT for patients with AML, ALL, high-risk MDS, and mixed-phenotype acute leukemia.

Precision-T phase 3 trial design and cGVHD-free survival results

The approval was supported by data from the phase 3 Precision-T trial (NCT04013685), a randomized, open-label, multicenter study evaluating Tregzi against conventional alloHSCT strategies in adults with hematological malignancies. All patients (n = 187) with a median age of 43.5 years (range, 19–65 years) were randomized 1:1 to Tregzi plus single-agent tacrolimus (TAC) or standard alloHSCT plus TAC/methotrexate (TAC/MTX).²

Tregzi is manufactured from mobilized peripheral blood of matched related or unrelated donors and consists of individually formulated highly purified regulatory T cells (Tregs), hematopoietic stem and progenitor cells, and conventional T cells (Tcons), produced at a centralized Good Manufacturing Practices facility. This centralized manufacturing model scales the precision Treg-based approach beyond single-institution use for the first time.

The 1-year cGVHD-free survival rate was 78% (95% CI, 65%–87%) with Tregzi vs 38% (95% CI, 26%–51%) with alloHSCT alone (HR, 0.26; P < .00001). The cumulative incidence of moderate to severe chronic GVHD was 13% (95% CI, 5%–23%) with Tregzi vs 44% (95% CI, 31%–56%) with alloHSCT (HR, 0.19; P < .00002).²

Overall survival, secondary outcomes, and safety in Precision-T

The estimated 1-year overall survival (OS) rate was 94% (95% CI, 86%–97%) with Tregzi vs 83% (95% CI, 73%–90%) with alloHSCT alone (HR, 0.49; P = .11823). The GVHD and relapse-free survival (GRFS) rate at 1 year was 63% with Tregzi vs 31% in the control group, and the relapse-free survival rate with Tregzi was 76%.²

Secondary outcomes showed fewer rehospitalizations due to safety events and reduced rates of non-relapse mortality with Tregzi vs conventional alloHSCT, though the OS difference did not reach statistical significance at 1 year. No new safety signals were identified with Tregzi in the Precision-T trial. Serious infection rates and non-relapse mortality were lower in the Tregzi arm compared with the TAC/MTX control.

"Today, treating patients with serious blood cancers using allogeneic stem cell transplants often forces a difficult risk–benefit trade-off, as clinicians work to cure the disease while avoiding life-threatening complications like GvHD," Everett Meyer, MD, PhD, hematologist and associate professor of medicine in Blood and Marrow Transplantation and Cellular Therapy at Stanford Medicine, said in a statement. "The Precision-T results showed Orca-T can meaningfully shift that balance, delivering improved GvHD-free survival alongside less toxicity, including fewer serious infections and lower non-relapse mortality."

Tregzi's mechanism centers on the role of donor-derived, polyclonal CD4+CD25+FoxP3+ Tregs in modulating T-cell alloreactivity to mitigate GVHD while maintaining graft-versus-leukemia activity and promoting immune reconstitution. The approval converts a concept previously limited to single-institution studies into a commercially scalable therapy, removing a longstanding barrier to broader clinical adoption of Treg-based transplantation.

References

1. FDA. FDA approves allogeneic regulatory T cell-based immunotherapy with HSPC and T cells-vldq for use in matched donor hematopoietic stem cell transplantation for adults with hematologic malignancies. June 30, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-allogeneic-regulatory-t-cell-based-immunotherapy-hspc-and-t-cells-vldq-use-matched

2. Meyer E, et al. Orca-T vs allogeneic hematopoietic stem cell transplantation (Precision-T): a multicenter, randomized phase 3 trial. Blood. 2026;147(11):1168. doi:10.1182/blood.2025027894