Orca-T Earns FDA Priority Review in Heme Malignancies

The FDA has accepted for priority review the biologics license application (BLA) for Orca-T, an investigational allogeneic T-cell immunotherapy, for the treatment of hematologic malignancies including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndromes (MDS).¹

The FDA has set a Prescription Drug User Fee Act target action date of April 6, 2026.

“A stem cell transplant has been the only potentially curative option for many people with AML, ALL or MDS; however, treatment-related toxicities too often hinder patient recovery. Acceptance of the Orca-T BLA marks a pivotal moment in our ability to deliver a first-in-class therapy designed to improve survival free from complications like graft-vs-host disease [GVHD],” Nate Fernhoff, PhD, cofounder and CEO at Orca Bio, said a press release.

“Supported by positive phase 3 clinical data [NCT0401368], today’s regulatory milestone reflects important recognition of the transformative potential of Orca-T. We look forward to working collaboratively with the FDA on the review of our application with the goal of advancing Orca-T and making it available to patients in need,” Fernhoff added.

The phase 3 Precision-T study met its primary end point of survival free of chronic GVHD (cGVHD). In the Orca-T arm, 78% (95% CI, 65%-87%) of patients achieved survival free of cGVHD compared with 38% (95% CI, 73%-90%) in patients who underwent allogeneic hematopoietic stem cell transplant (alloHSCT).²

As of March 2025, an interim analysis of the secondary end point of overall survival (OS) showed that OS was 94% (95% CI, 86%-97%) in the Orca-T arm vs 83% (95% CI, 73%-90%) in the alloHSCT arm (HR, 0.49; P =.11823). The rates of cumulative incidence of moderate to severe cGVHD were 13% (95% CI, 5%-23%) in the Orca-T arm vs 44% (95% CI, 31%-56%) in the alloHSCT arm (HR, 0.19; P <.00002).

Precision-T, a randomized, open-label, multicenter study, evaluated the safety, efficacy, and tolerability of Orca-T vs conventional alloHSCT across multiple hematologic malignancies.³ Across both groups, patients received myeloablative conditioning and used a related or unrelated matched donor.

Orca-T was previously granted regenerative medicine advanced therapy and orphan drug designations from the FDA for the prevention of GVHD or death in patients eligible for hematopoietic stem cell transplant.²

Additional findings from Precision-T showed that for exploratory end points at 1 year, the rate of relapse-free survival was 76% vs 74% in the Orca-T and alloHSCT arms, respectively (HR, 0.80; P =.49). In the Orca-T and alloHSCT arms, the cumulative incidence of nonrelapse mortality was 3% and 13%, respectively, and the cumulative incidence of grade 3 or 4 acute GVHD was 6% and 17%, respectively.

There were also no new safety issues seen with Orca-T. Infections deemed grade 4 or greater per CTCAE scoring were observed in 6% and 10% of patients in the Orca-T and alloHSCT arms, respectively.

Data from a retrospective analysis presented at the 2024 American Society of Hematology Annual Meeting and the 2025 Transplantation & Cellular Therapy Tandem Meetings showed that Orca-T yielded improved OS vs posttransplant cyclophosphamide (PTCy).^4,5 The cohorts used for comparison were from a phase 1b study (NCT04013685) and patient data from the Center for International Blood & Marrow Transplant Research registry.

The 1-, 2-, and 3-year OS rates were 96% (95% CI, 88%-99%), 88% (95% CI, 78%-94%), and 86% (95% CI, 73%-92%), respectively, in the cohort of Orca-T–treated patients (n = 77). Patients from the CIBMTR registry who received PTCy after alloHSCT (n = 293) achieved 1-, 2-, and 3-year OS rates of 82% (95% CI, 78%-87%), 73% (95% CI, 68%-79%), and 67% (95% CI, 61%-74%), respectively.

REFERENCES:

1. Orca Bio announces FDA acceptance and priority review of the biologics license application (BLA) for Orca-T to treat hematological malignancies. News release. Orca Bio. October 6, 2025. Accessed October 6, 2025. https://tinyurl.com/mpkppnky

2. Orca Bio announces positive results from the pivotal phase 3 study of investigational Orca-T compared to allogeneic stem cell transplant for the treatment of hematologic malignancies. News release. Orca Bio. March 17, 2025. Accessed October 6, 2025. https://tinyurl.com/yf2mr3kk

3. Precision-T: a randomized study of Orca-T in recipients undergoing allogeneic transplantation for hematologic malignancies (Orca-T). ClinicalTrials.gov. Updated September 26, 2025. Accessed October 6, 2025. https://clinicaltrials.gov/study/NCT05316701

4. Meyer E, Srour S, Oliai C, et al. Observational comparison of overall survival between phase 1b Orca-T and registry-based post-transplant cyclophosphamide patients. Presented at: Presented at: 2025 Transplant and Cellular Therapy Meetings; February 12-15, 2025; Honolulu, HI. Abstract 25027.

5. Oliai CH, Hoeg RT, Gandhi A, et al. Observational comparison of overall survival between phase 1b Orca-T and registry-based post-transplant cyclophosphamide patients. Blood. 2024;144(suppl 1):694. doi:10.1182/blood-2024-205917