FDA Approves Tregzi, First Regulatory T-Cell Immunotherapy to Reduce Chronic Graft-Versus-Host Disease in Allogeneic Stem Cell Transplantation

FDA has approved Orca Biosystems’ Tregzi, an allogeneic regulatory T cell immunotherapy with hematopoietic stem and progenitor cells (HSPC) and T cells-vldq, making it the first regulatory T (Treg) cell–based immunotherapy indicated to improve chronic graft-versus-host disease (GVHD)-free survival in adult patients with blood cancers who are undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). The approval, supported by data from the randomized PRECISION-T trial, addresses a significant complication of allo-HSCT, chronic GVHD. The complication causes debilitating systemic inflammation when transplanted donor immune cells attack recipient tissues.¹

"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 FDA’s Center for Biologics Evaluation and Research, in an agency press release.¹ "[This] approval offers a genuine new approach that can help reconstitute the immune system while substantially reducing that risk."

What did the PRECISION-T trial demonstrate regarding Tregzi's efficacy and safety?

PRECISION-T was a randomized controlled trial enrolling 187 adult patients with blood cancers, including acute leukemia and myelodysplastic syndrome. The patients were assigned to receive either Tregzi or a standard stem cell transplant. The primary endpoint was chronic GVHD-free survival, defined as time from allo-HSCT to death from any cause or first onset of moderate or severe chronic GVHD within 2 years. At 1 year, 78.0% of Tregzi recipients achieved chronic GVHD-free survival versus 38.4% of standard transplant recipients.

After accounting for death as a competing risk, serious chronic GVHD developed in 12.6% of Tregzi-treated patients versus 44.0% in the control arm. No severe infusion reactions occurred, and no cases of graft failure were observed. Adverse events were consistent with the established allo-HSCT profile, with infections as the most common finding, according to the agency.¹

What is Tregzi's composition and mechanism, and how does it differ from standard stem cell transplant approaches?

Tregzi is a donor-derived cellular immunotherapy comprising 3 components from mobilized peripheral blood of an 8/8 human leukocyte antigen (HLA)-matched related or unrelated donor. The components include purified HSPCs, Treg cells, and conventional T (Tcon) cells. Treg cells are a specialized CD4+ subset that maintain peripheral immune tolerance by suppressing alloreactive immune responses.²

In conventional allo-HSCT grafts, relative Treg cell scarcity is hypothesized to permit unchecked Tcon cell–mediated alloreactivity against host tissues, producing chronic GVHD.³ By supplementing the graft with purified donor-derived Treg cells, Tregzi aims to rebalance immune reconstitution toward tolerance while preserving the graft-versus-leukemia effect.³

What is the unmet need in allo-HSCT, and what limitations apply to this approval?

Chronic GVHD affects an estimated 30% to 70% of allo-HSCT recipients and is the leading cause of non-relapse mortality and long-term disability in transplant survivors.⁴ Existing pharmacologic prophylaxis strategies reduce but do not eliminate risk, and treatment of established chronic GVHD remains difficult.⁵

PRECISION-T enrolled patients receiving 8/8 HLA-matched grafts, which limits generalizability to mismatched or haploidentical transplant settings. Longer follow-up would be needed to characterize overall survival benefit and relapse rates beyond the trial window. As a complex multi-component cellular product, Tregzi would require careful logistical implementation across transplant centers, including apheresis coordination and cell processing infrastructure. Tregzi was granted orphan drug and regenerative medicine advanced therapy (RMAT) designations by FDA.¹

References

1. FDA. FDA approves new treatment that uses donor immune cells to prevent serious complications in blood cancer patients. Published June 30, 2026. Accessed July 1, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-uses-donor-immune-cells-prevent-serious-complications-blood-cancer
2. Sakaguchi S, Mikami N, Wing JB, Tanaka A, Ichiyama K, Ohkura N. Regulatory T cells and human disease. Annu Rev Immunol. 2020;38:541-566. doi:10.1146/annurev-immunol-042718-041717
3. Edinger M, Hoffmann P. Regulatory T cells in stem cell transplantation: strategies and first clinical experiences. Curr Opin Immunol. 2011;23(5):679-684. doi:10.1016/j.coi.2011.06.006
4. Zeiser R, Blazar BR. Pathophysiology of chronic graft-versus-host disease and therapeutic targets. N Engl J Med. 2017;377(26):2565-2579. doi:10.1056/NEJMra1703472
5. Wolff D, Radojcic V, Lafyatis R, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease : IV. The 2020 Highly morbid forms report. Transplant Cell Ther. 2021 Oct;27(10):817-835. doi:10.1016/j.jtct.2021.06.001