FDA Grants Priority Review to BLA for Orca-T in Hematologic Malignancies

The FDA has accepted a biologics license application (BLA) for Orca-T, an allogeneic T-cell immunotherapy, for priority review as a treatment for multiple hematological malignancies including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndromes (MDS), according to a news release from the drug’s developer, Orca Bio.¹

The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of April 6. 2026 for Orca-T as a treatment for patients with AML, ALL, and MDS.

The BLA acceptance is supported by findings from the phase 3 Precision-T trial (NCT04013685), which evaluated the safety, efficacy, and tolerability of Orca-T with other conventional allogenic hematopoietic stem cell transplantation (HSCT) strategies among patients with AML, ALL, and MDS. The study’s primary end point was met, with a statistically significant improvement in moderate-to-severe graft chronic graft-versus-host disease (cGVHD)–free survival seen with Orca-T vs standard-of-care (SOC) allogenic HSCT.

Efficacy data from the trial revealed that Orca-T exhibited a 1-year GVHD-free survival of 78% (95% CI, 65%-87%) vs 38% (95% CI, 26%-51%) with allogenic HSCT (HR, 0.26; P <.00001).² An estimated 1-year overall-survival (OS) benefit was observed with Orca-T vs SOC, with rates of 94% (95% CI, 86%-97%) vs 83% (95% CI, 73%-90%) with allogenic HSCT (HR, 0.49; P = .11823). Additionally, a cumulative incidence of moderate-to-severe cGVHD at 13% (95% CI, 5%-23%) and 44% (95% CI, 31%-56%) in each of the respective arms was observed (HR, 0.19; P <.00002).

“A stem cell transplant has been the only potentially curative option for many [patients] 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 [GVHD],” Nate Fernhoff, PhD, co-founder and chief executive officer at Orca Bio, stated in the news release on the regulatory decision.¹ “Supported by positive phase 3 clinical data, 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.”

Patients with acute myeloid, lymphoid, or mixed phenotype leukemia in complete remission (CR) or CR with incomplete hematologic recovery and those with MDS and/or therapy-related or secondary MDS with 10% or less blast burden in the bone marrow were enrolled on trial.³ Patients were randomly assigned 1:1 to receive either Orca-T or SOC allogenic HSCT.

Orca-T was given following myeloablative conditioning, and a single-agent GVHD prophylaxis with tacrolimus (Prograf) was administered following infusion. In the SOC arm, an unmanipulated allograft derived from peripheral blood of a matched donor was given after myeloablative conditioning, and a dual-agent prophylaxis composed of tacrolimus plus methotrexate was given on day –3.

Patients in the study had a median age of 43.5 years (range, 19-65). The median follow-up for the study was 11.4 months (range, 0.2-24.3).

The primary end point of the trial was 12-month moderate-to-severe GVHD survival. Secondary end points included 12-month moderate-to severe GVHD event rate, 12-month OS, and 12-month disease-free and relapse-free survival rates.

Safety findings from the trial revealed that no new signals were identified with Orca-T. Additionally, infections of grade 4 or higher in severity per CTCAE criteria were reported in 6% of patients treated with the investigational agent vs 10% of those who received SOC allogenic HSCT.

Reference

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/urwb7244
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/26edwyup
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://tinyurl.com/y9ubftdy