Orca Bio’s Tregzi gets FDA nod as first allogeneic regulatory T cell therapy for transplant patients

Edited by Robert McTiernan··2 min read

The US FDA approved Tregzi (HSPC and T cells-vldq), developed by Orca Bio, for use in matched donor hematopoietic stem cell transplantation with a myeloablative preparative regimen in adults with hematological malignancies. The approval marks the first allogeneic regulatory T cell-based immunotherapy to receive regulatory clearance for this setting, representing a distinct cell engineering approach in a field where chronic graft-versus-host disease (cGVHD) remains a leading cause of non-relapse mortality and long-term morbidity after transplant.

Tregzi is administered as three sequential infusions consisting of hematopoietic stem and progenitor cells and regulatory T cells on day 0, followed by conventional T cells two to three days later. As previously reported, the FDA had extended its review of the biologics license application to July 2026.

The product’s mechanism centers on precision-sorted immune cell populations derived from a matched allogeneic donor. By delivering a defined ratio of Tregs alongside HSPCs and Tcons, the approach is designed to suppress alloreactive T cell responses responsible for cGVHD while preserving the graft-versus-leukemia effect — an immunological balance that conventional pharmacologic prophylaxis has not reliably achieved.

Efficacy was demonstrated in Precision-T (NCT05316701), a multicenter, open-label, randomized, controlled Phase III trial enrolling adults with acute leukemias or myelodysplastic syndrome. The trial randomized 187 adults with acute leukemia or myelodysplastic syndrome to receive either Tregzi plus tacrolimus alone or an unmanipulated allograft followed by tacrolimus and methotrexate.

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The primary endpoint — cGVHD-free survival (cGFS), defined as time to death from any cause or moderate-to-severe cGVHD — strongly favored Tregzi. Median cGFS was not estimable in the Tregzi arm versus 7.3 months in the control arm (HR 0.26; 95% CI: 0.14, 0.47; P < .00001). The 12-month cumulative incidence of moderate-to-severe cGVHD was 12.6% with Tregzi versus 44.0% in the control arm (HR 0.19; P = .00002). All 88 evaluable patients achieved neutrophil engraftment within 28 days, confirming reliable hematopoietic reconstitution.

The approval positions Tregzi in a landscape where prophylactic options have been limited. Bristol Myers Squibb’s abatacept (Orencia) is the only other FDA-approved agent specifically indicated for GVHD prophylaxis in the allogeneic HSCT setting, approved in 2021 for acute GVHD prevention in matched or one-allele mismatched unrelated donor transplants. Tregzi’s approval extends the prophylactic endpoint to chronic GVHD-free survival, addressing a clinically distinct and longer-term complication. In the broader GVHD treatment space, ruxolitinib and other JAK inhibitors address established disease rather than prevention. In the cell therapy space, dorocubicel (Zemcelpro) is another investigational cell therapy being developed for allogeneic HSCT recipients, with Phase II data suggesting low rates of moderate-to-severe cGVHD, though it has not yet received FDA approval.

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