First FDA-Approved Cell Therapy to Reduce Chronic Graft-Versus-Host Disease

TREGZI (allogeneic regulatory T cell immunotherapy with HSPC and T cells-vldq) is a donor-matched cell therapy given as sequential intravenous infusions. On the US Package Insert it is indicated for use in matched donor hematopoietic stem cell transplantation with myeloablative preparative regimen, for hematopoietic and immunologic reconstitution and to improve chronic graft-versus-host disease-free survival, in the treatment of adults with hematological malignancies.

This is a traditional FDA approval (Priority Review, Orphan Drug, and Regenerative Medicine Advanced Therapy designations) — not an accelerated approval.

Distinct path — not this carton (fact-only): A conventional unmanipulated matched-donor allograft with tacrolimus plus methotrexate is not this four-bag TREGZI product. Autologous gene therapies and haploidentical or mismatched-donor grafts are not this labelled 8/8 HLA-matched door. Today’s US labelled Treg-based precision allograft door for adults with hematologic malignancies undergoing matched-donor myeloablative transplant is Orca Biosystems TREGZI STN 125868.

The FDA approved STN BL 125868/0 on 30 June 2026. A replacement approval letter dated 1 July 2026 corrects the manufacturing site to Sacramento, CA; the effective approval date remains 30 June 2026. Approval letter issues U.S. License Number 2404 to Orca Biosystems Inc., Menlo Park, CA. Letter attention: Karin Mcintosh, MPharm, RAC. Associated NCT numbers on the letter: NCT04013685, NCT05316701. Package Insert revised 06/2026. Manufactured by Orca Biosystems Inc., 7910 Metro Air Parkway, Sacramento, CA 95837.

Where this is taking place

Commercial labelled door today: United States — FDA-labelled TREGZI for adults with hematologic malignancies undergoing matched-donor HSCT after a myeloablative preparative regimen, administered at a transplant centre that can receive the four patient-specific infusion bags (HSPCs, Tregs, Tcons, Tcon diluent), give Day 0 and Day +2/+3 infusions, and start tacrolimus prophylaxis. Company and trade coverage after approval described a phased commercial start at a handful of centres with a planned ramp toward about 25 centres by the end of 2026. Treat mid-September 2026 as a launch-window / referral conversation, not a guarantee every transplant hospital can infuse TREGZI this week. This is a bone-marrow transplant / cell-therapy conversation — not a retail pickup and not a DIY import.

Outside the United States: As of this draft, no confirmed Health Canada Notice of Compliance, European Commission marketing authorisation, MHRA licence, TGA listing, Swissmedic authorisation, or PMDA/MHLW licence for TREGZI / Orca-T. Do not import on your own.

Precision-T — NCT05316701 — Randomized, open-label, multicenter Phase 3 study. Lead sponsor: Orca Biosystems, Inc. CT.gov status at draft time: ACTIVE, NOT RECRUITING. Actual enrolment 187. Actual start 21 Jun 2022; actual primary completion 15 Jul 2024; estimated study completion Jul 2026. Locations listed: United States only (19 centres on the record retrieved). Expanded access on this record: CT.gov reports hasExpandedAccess: false. Honesty: The labelled efficacy set is a completed primary analysis within follow-up — that is not open new-enrolment, and it is not the same sentence as “walk into any transplant ward for TREGZI.”

NCT04013685 — Phase 1b program associated on the approval letter. CT.gov status: ACTIVE, NOT RECRUITING. Actual enrolment 155. United States sites. This record lists expanded access NCT07346105 as AVAILABLE.

NCT07346105 — Expanded-access record for commercially prescribed Orca-T that does not meet commercial release specifications or is delivered past expiry, when remanufacturing is not clinically appropriate. Contacts on the record: James S. McClellan, MD, PhD and Anna Pavlova, MD, PhD, 530-414-9723, info@orcabio.com. Honesty: This is not a general compassionate-access program for people who cannot get commercial TREGZI. It is a manufacturing out-of-specification path for a product already prescribed.

The practical commercial door in the US is a transplant / hematology centre working with Orca Bio to confirm an 8/8 HLA-matched sibling or unrelated donor, plan myeloablative conditioning, receive the four patient-specific bags, infuse on the labelled Day 0 / Day +2–+3 schedule, and monitor for graft failure, GVHD, infection, and infusion reactions — not treating ACTIVE_NOT_RECRUITING as open enrolment.

Approval matrix

Access by country

• United States: Ask a transplant / hematology clinic about referral for FDA-labelled TREGZI. Labelled 30 June 2026 for adults with hematological malignancies undergoing matched-donor HSCT after a myeloablative preparative regimen, to reconstitute blood/immune function and improve cGVHD-free survival. Path: 8/8 HLA-matched sibling or unrelated donor apheresis → Orca Bio manufacture (HSPC/Treg dating 72 hours from first apheresis at 2–8 °C; Tcon 7 days frozen below −125 °C) → myeloablative conditioning → HSPC then Treg IV on Day 0, Tcon (with diluent) IV on Day +2 to +3 if no uncontrolled infection and Karnofsky ≥30% → tacrolimus within 12 hours after Tcon. Verify patient identity on every bag. Do not use a leukodepleting filter. Kit NDC 85866-223-04. Suspected adverse reactions: Orca Bio 1-877-290-6722 or FDA MedWatch 1-800-FDA-1088. Secondary malignancy or donor-origin malignancy, and pregnancies after TREGZI: Orca Bio 1-877-411-6722 (Package Insert). No list price or copay dollars in this article. Company/trade coverage may discuss centre count — disclose the phased launch honestly with the centre. This is US labelled supply through transplant centres, not a DIY import.

• Canada: TREGZI authorisation not confirmed. Ask the Canadian transplant clinic what legal paths exist in Canada when a Canadian TREGZI label does not yet exist.

• European Union / United Kingdom / Australia / Japan / other countries: Regulator authorisation not confirmed in this draft. US trial sites are not a commercial foreign carton. Do not import on your own.

• If your regulator has not authorised it: do not import on your own. Ask the local clinician about documented special-access / named-patient rules, referral to a centre in a labelled country, or waiting — without treating a US four-bag product as a foreign carton.

Who is eligible (from the US label)

This is an adult matched-donor myeloablative transplant conversation on the Package Insert — sequential HSPC / Treg / Tcon infusions — not a pediatric carton and not a haploidentical or mismatched-donor claim.

United States (Package Insert, revised June 2026):

• Indication: Matched-donor HSCT with myeloablative preparative regimen, for hematopoietic and immunologic reconstitution and to improve cGVHD-free survival, in adults with hematological malignancies.
• Recommended dosage: HSPC ≥1.0×10⁶ viable cells/kg IV Day 0; Treg 1.3×10⁶–3.5×10⁶/kg IV Day 0 immediately after HSPCs; Tcon 1.3×10⁶–6.9×10⁶/kg IV Day +2 to +3 (after start of HSPC infusion on Day 0), diluted with Tcon diluent. Patient-specific Certificate of Analysis governs the batch.
• Contraindication: None listed on Highlights.
• Warnings: Graft failure (screen for antidonor antibodies; monitor recovery); acute and chronic GVHD including life-threatening cases (single-agent calcineurin-inhibitor prophylaxis); infusion reactions including hypersensitivity to DMSO, albumin, dextran, or murine protein (premedicate with antipyretics and histamine antagonists); secondary malignancies and malignancies of donor origin (including PTLD risk after transplant in general; no PTLD in TREGZI-treated patients on PI); transmission of infectious agents from donor blood and animal-derived reagents.
• Most common adverse reactions (≥20%): mucositis, diarrhea, rash, viral infections, infections-pathogen unspecified, abdominal pain, vomiting, nausea, bacterial infections, hemorrhage, acute GVHD, edema, fungal infections.
• Most common Grade 3–4 laboratory abnormalities (≥20%): lymphocyte count decreased, platelet count decreased, leukocyte count decreased, neutrophil count decreased, hemoglobin decreased.
• Pregnancy / lactation / contraception: Use during pregnancy only if potential benefit justifies potential risk to the fetus; report pregnancies to Orca Bio 1-877-411-6722. Contraception duration after TREGZI is not separately specified — follow the selected conditioning-regimen prescribing information. Fertility effects unknown.
• Pediatrics: Safety and effectiveness not established.
• Geriatrics: Precision-T did not include patients ≥65; other studies enrolled some adults over 65 but numbers were inadequate for a labelled geriatric recommendation.

Precision-T trial context (USPI): Adults with ALL, AML, mixed-phenotype/undifferentiated leukemia in CR/CRi, or MDS meeting labelled high-risk criteria; no prior allogeneic HSCT; 8/8 HLA-matched sibling or unrelated donor; myeloablative TBI-based or chemotherapy-based conditioning. Median age 44 years (range 19–65); 54% AML, 31% ALL, 12% MDS, 4% MPAL.

Not labelled on sources confirmed for this draft:

• Children and adolescents.
• Patients without an 8/8 HLA-matched sibling or unrelated donor.
• Reduced-intensity conditioning as a labelled TREGZI door (geriatric RIC mentioned only as inadequate for a recommendation).
• Canadian, EU, UK, Japanese, Australian, or Swiss TREGZI marketing authorisations (not confirmed here).
• Treating NCT05316701 follow-up as open commercial enrolment.
• Treating NCT07346105 as a general compassionate-access program.

What the pivotal study showed (Prescribing Information)

Use the Package Insert for a prescription conversation. Journals are supportive reading.

Precision-T — NCT05316701 (USPI Study):

• Open-label, randomized, controlled, multicenter; TREGZI + tacrolimus vs unmanipulated allograft + tacrolimus/methotrexate.
• Randomized 187 (TREGZI 93 / control 94); 88 received TREGZI.

USPI efficacy (intention-to-treat):

Median follow-up 8.48 months (TREGZI) vs 9.03 months (control). Neutrophil ≥500/mm³ within 28 days: 88/88 (100%) treated with TREGZI. Non-relapse deaths at 12 months: 3/88 (3.4%) TREGZI vs 11/94 (11.7%) control.

Trial-status honesty: CT.gov status ACTIVE, NOT RECRUITING at draft time. Traditional approval ≠ every transplant centre can infuse this week.

How it is taken (US label — keep this exact)

Research team (from primary sources only)

• Applicant / manufacturer: Orca Biosystems Inc. — Menlo Park, CA (license holder); Sacramento, CA manufacturing (7910 Metro Air Parkway); U.S. License 2404.
• Pivotal study sponsor: Orca Biosystems, Inc. (NCT05316701 / Precision-T).
• Letter attention: Karin Mcintosh, MPharm, RAC (replacement approval letter 1 Jul 2026).
• OOS expanded-access contacts (NCT07346105): James S. McClellan, MD, PhD; Anna Pavlova, MD, PhD — 530-414-9723, info@orcabio.com.
• Patient / AE contacts on label: Orca Bio 1-877-290-6722 (suspected adverse reactions); 1-877-411-6722 (secondary malignancy / donor-origin malignancy / pregnancy).
• Names and phones below are limited to what appears on the Package Insert, FDA approval notice / letter, ClinicalTrials.gov, and clearly labelled company materials.

Sources

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 (30 Jun 2026).
2. FDA — FDA Approves New Treatment That Uses Donor Immune Cells to Prevent Serious Complications in Blood Cancer Patients (press, 30 Jun 2026).
3. FDA — July 1, 2026 Approval Letter — TREGZI (STN BL 125868/0; License 2404; effective 30 Jun 2026).
4. FDA — TREGZI Package Insert (revised 6/2026).
5. ClinicalTrials.gov — NCT05316701 (Precision-T); NCT04013685; NCT07346105.
6. Orca Bio — FDA approval company announcement (30 Jun 2026).

Not medical advice. Talk with a clinician who knows the full history before any treatment decision. Authorized is not funded.