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High-Cost Therapy Profile: March 2026

Allogeneic T-cell immunotherapy (Orca-T) Intravenous (IV) | Orca Bio  

Oncology-Gene therapy 
March 11, 2026

Proposed indications 

Hematological malignancies, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and myelodysplastic syndromes (MDS). 

FDA approval timeline

April 6, 2026 

  • Priority Review 
  • Orphan Drug
  •  Regenerative Medicine Advanced Therapy (RMAT)

Place in therapy 

Orca-T is an allogeneic T cell immunotherapy that contains purified regulatory T cells, hematopoietic stem cells and conventional T cells derived from peripheral blood from either related or unrelated matched donors.  

  • If approved, Orca-T, a precision-engineered graft, will be the first allogeneic T cell immunotherapy for the treatment of hematologic malignancies, including AML, ALL and MDS. 
  • If approved, Orca-T may improve outcomes compared to traditional allogeneic hematopoietic stem cell transplants (allo-HSCT) in adults with high-risk hematologic cancers. 
  • In the Precision-T trial, a regimen of Orca-T with tacrolimus led to significantly fewer cases of chronic graft versus host disease (GVHD) at 12 months and fewer serious side effects compared to a regimen of allo-HSCT with tacrolimus and methotrexate in patients with AML, ALL or MDS. 
  • Like allo-HSCT, Orca-T is derived from allogeneic donors, and both use conventional T cells. Orca-T differentiates itself from allo-HSCT with the addition of highly purified, polyclonal donor regulatory T cells to prevent GVHD with significantly less immunosuppression. The main components of Orca-T are delivered in separate sequential steps with first migration of regulatory T cells, allowing for immune barrier protection prior to delivery of conventional T cells. 
  • After the manufacturing of Orca-T, the product was consistently distributed and infused in less than 72 hours for vein-to-vein time between end of donor apheresis to start of recipient’s infusion.  

Understanding your data

Orca-T is a high-precision engineered cell therapy that is made of stem and immune cells taken from a related or unrelated matched donor. The use of highly purified, polyclonal donor regulatory T cells helps to control alloreactive immune responses. Studies evaluating Orca-T in improving survival without the complication of GVHD include the following: 

  • NCT04013685 Precision-T: A Phase 1b trial of patients with advanced hematologic malignancies undergoing allogeneic hematopoietic cell transplantation with either Orca-T, a T-cell-depleted graft with additional infusion of conventional T cells and regulatory T cells or standard-of-care allogeneic graft. 
  • NCT05316701 Precision-T: A randomized Phase 3 trial of patients with advanced hematologic malignancies undergoing allogeneic hematopoietic cell transplantation with either Orca-T, a T-cell-depleted graft with additional infusion of conventional T cells and regulatory T cells, or standard-of-care allogeneic graft. 
  • NCT07216443: A Phase 2 trial of Orca-T following reduced intensity or nonmyeloablative conditioning in patients with acute myeloid leukemia or myelodysplastic syndrome. 
  • NCT06195891: A single center, non-randomized, Phase 1b study of Orca-T following escalated dose of total marrow and lymphoid irradiation in patients with acute leukemias and MDS. 

Identification of patients would reflect the clinical trials criteria listed in the studies above, as well as diagnosis codes identified from claims data requiring among others: 

Common Measurable Inclusion Criteria: 

  • Age ≥ 18 years. 
  • Diagnosis of acute myeloid, lymphoid, or mixed phenotype/undifferentiated leukemia. 
  • Diagnosis of myelodysplastic syndrome. 
  • Diagnosis of blastic plasmacytoid dendritic cell neoplasm. 
  • Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min. 

Common Measurable Exclusion Criteria: 

  • Prior allo-HSCT. 
  • Recipient is positive for anti-donor human leukocyte antigen (HLA) antibodies. 
  • Human immunodeficiency virus 1 and 2 (HIV-1/HIV-2); Human T-lymphotropic virus 1 and 2 (HTLV-1/HTLV-2). 
  • Pregnancy or lactation. 

Appendix


Category Procedure codes
Hematologic malignancies International Classification of Diseases, Tenth Revision (ICD-10): C86.4, C91, C92, C94.6, C95, D46
eGFR < 60 mL/min ICD-10: N18.3, N18.4, N18.5, N18.6, Z49
allo-HSCT ICD-10:Z94.84
Current Procedural Terminology (CPT): 38240
ICD-Procedure Coding System (PCS) ICD-10-PCS: 30233X2, 30233X3, 30243X2, 30243X3
HIV-1 and HIV-2 ICD-10: B20, B97.35, Z21
HTLV-1 and HTLV-2 ICD-10: C91.5, B97.33, B97.34
Pregnancy and lactation ICD-10:Z34.00, Z34.8, Z34.90, Z33.1, O09.00, O09.10, O09.291, O09.40, O09.211, O09.30, O09.511, O09.521, O09.611, O09.621, O09.819, O09.821, O09.822, O09.823, O09.829, O36.80x0, O09.891, O09.892, O09.893, O09.899, Z39.0, Z39.1, Z39.2, Z36, Z37, Z37.1, Z37.2, Z37.3, Z37.4, Z37.59, Z37.69, Z37.7, Z37.9, Z64.0, Z32.01, O30.009, O30.019, O30.039, O30.049, O30.099, O30.109, O30.119, O30.129, O30.199, O30.209, O30.219, O30.229, O30.299, O30.809, O30.819, O30.829, O30.899, O20.0, O44.01, O44.02, O44.03, O10.011, O10.012, O10.013, O10.02, O10.911, O10.912, O10.913, O10.92, O10.03, O21.0, O60.12X0, O60.13X0, O60.14X0, O48.0, O31.01X0, O31.02X0, O31.03X0, O98.111, O98.112, O98.113, O98.12, O98.13, O24.32, O24.911, O24.912, O24.913, O24.92, O24.93, O99.331, O99.332, O99.333, O99.334, O99.335, O80, O30.001, O30.002, O30.003, O32.0XX0, O33.0, O34.01, O34.02, O34.03, O34.01, O34.02, O34.03, O35.0XX0, O43.011, O36.0110, O36.0120, O36.0130, O36.0910, O36.0920, O36.0930, O36.1110, O36.1120, O36.1130, O36.1910, O36.1920, O36.1930, O68, O36.5110, O36.5120, O36.5130, O36.5910, O36.5920, O36.5930, O36.61X0, O36.62X0, O36.63X0, O43.101, O43.102, O43.103, O43.811, O43.812, O43.813, O43.91, O43.92, O43.93, O36.8910, O36.8920, O36.8930, O68, O77.0, O36.91X0, O36.92X0, O36.93X0, O40.1XX0, O40.2XX0, O40.3XX0, O41.01X0, O41.02X0, O41.03X0, O61.1, O64.9XX0, O62.0, O63.0, O70.0, O71.02, O71.03, O72.0, O43.211, O43.212, O43.213, O43.221, O43.222, O43.231, O43.232, O43.233, O73, O74.1, O89.09, O75.0, O86.89, O22.01, O22.02, O22.03, O87.4, O86.4, O88.011, O88.012, O88.013, O88.02, O88.03, O99.411, O99.412, O99.413, O99.42, O99.43, O91.011, O91.012, O91.013, O91.02, O92.011, O92.012, O92.013,O92.03, O35.8XX0, O36.8210, O36.8220, O36.8230, O75.89, Z37.0, Z37.2, Z37.3, Z37.59, Z37.69, O86.12, O85, O86.81, O86.89

Clinical deep dive 

Disease state overview

Hematologic malignancies are cancers originating from blood forming cells that affect the blood, bone marrow or lymphatic system and include AML, ALL and MDS. These cancers occur when abnormal, immature white blood cells overgrow, bone marrow produces excessive immature lymphocytes or immature blood cells fail to mature, respectively, overtaking normal blood cell development. Hematologic malignancies are the most frequent indications for an allo-HSCT. An allo-HSCT is a procedure that replaces diseased stem cells with related or unrelated healthy donor stem cells collected from blood, bone marrow or umbilical cord blood. These stem cells will be infused into the bloodstream, travel to the bone marrow and give rise to new blood cells.  

GVHD is a life-threatening multisystem complication of allo-HSCT. GVHD impacts transplantation-related mortality, relapse rate and overall survival. It is divided into two main categories based on signs and symptoms (no longer based on time of onset), such as acute GVHD and chronic GVHD. Acute GVHD is driven mainly by mature donor T cells and is represented by rapid onset because of a cytokine storm that manifests in three organs (skin, liver and gastrointestinal [GI] tract). Patients can exhibit a maculopapular skin rash, bile duct damage leading to cholestasis and jaundice, nausea and upper GI symptoms (vomiting, anorexia) and lower GI symptoms (watery or bloody diarrhea, abdominal pain). 

Epidemiology 

In the U. S., about 46,000 persons are diagnosed with AML, ALL and MDS each year. Only a fraction of hematologic malignancies will receive an allo-HCST. Approximately 8,000 people receive allo-HSCT each year in the US. 

Treatment

Allo-HSCT is a potentially curative treatment for patients with high-risk hematological malignancies, including AML, ALL and MDS. Patients scheduled for allo-HSCT receive cytotoxic conditioning regimens to eradicate residual malignant cells in the bone marrow and to suppress the immune system to allow for engraftment of healthy donor cells to take place. However, despite immune suppression, GVHD remains a major complication following allo-HSCT. 

Drug and clinical trial overview 

The ongoing, open-label Phase 3 Precision-T trial compared efficacy and safety of Orca-T to conventional allo-HSCT in adults with acute leukemias or MDS undergoing myeloablative conditioning. A total of 187 adults were randomized to Orca-T with tacrolimus or conventional allo-HSCT with tacrolimus and methotrexate (Tac/MTX), using granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood from HLA-matched donors. Patients were followed for up to 730 days after transplantation. In the Precision-T trial, Orca-T is administered via IV infusion after myeloablative conditioning followed by single-agent tacrolimus. The primary endpoint of moderate-to-severe chronic GVHD-free survival at 12 months was achieved in significantly more patients who received Orca-T than those who received allo-HSCT (78% versus 38.4%, respectively; hazard ratio, 0.26; p<0.00001). The secondary endpoint of GVHD-free and relapse-free survival at 12 months was significantly greater with Orca-T compared to allo-HSCT (63.1% versus 30.9%, respectively; p=0.00003). In addition, non-relapse mortality was 3.4% in the Orca-T arm compared to 13.2% in the allo-HSCT arm (p=0.03). However, the overall survival (OS) and relapse-free survival (RFS) at 12 months did not differ significantly between the groups (OS, 93.7% versus 83.2%, respectively; RFS, 75.5% versus 74.1%, respectively). The overall incidence of grade 3/4 adverse events, including severe infection and severe acute GVHD, were lower with Orca-T compared to allo-HSCT. The final completion of the Precision-T trial is estimated to be in July 2026. 

Pipeline (late-stage development)

Name Manufacturer Route of administration Mechanism of action Proposed / studied indication Status
5F9 (ONO-7913) in combination with azacitidine Forty-Seven/Gilead IV anti-CD47 antibody MDS Phase 1b
APR-246 in combination with azacitidine Aprea IV P53 reactivator MDS with TP53 mutation Phase 3

The information provided has been developed based on available information as of March 2, 2026. This therapy is NOT FDA approved, and content may change as more information becomes available. Caution should be used when developing formulary and utilization management strategies. 

The information contained in this report is intended for educational purposes only and is not intended to define a standard of care or exclusive course of treatment, nor be a substitute for treatment.

All brand names are property of their respective owners. 

References 

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