Biologics license application for Orca-T for hematological malignancies granted priority review by FDA

The U.S. Food and Drug Administration (FDA) has granted priority review to a biologics license application (BLA) seeking approval of the allogeneic T-cell immunotherapy Orca-T for the treatment of hematologic malignancies, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndromes (MDS).¹ 

The FDA assigned a target action date for the BLA of April 6, 2026, under the Prescription Drug User Fee Act (PDUFA).¹ The BLA submission is based on data from the pivotal phase III study, Precision-T (NCT04013685), a randomized, open-label, multicenter study evaluating Orca-T compared with conventional allogeneic hematopoietic stem cell transplant (allo-HSCT) for the treatment of AML, ALL, high-risk MDS, and mixed-phenotype acute leukemia.^1,2 

Precision-T key data²

Patients (N = 187) were randomized to receive Orca-T plus single-agent tacrolimus (Tac) or allo-HSCT + Tac + methotrexate. Both groups received myeloablative conditioning and received transplantation from a related or unrelated matched donor. The median follow-up was 11.4 months across both treatment arms. 

• The primary endpoint of survival free of chronic graft-versus-host disease (cGvHD) was 78% in patients who received Orca-T (n = 93) vs 38% in patients who received conventional allo-HSCT (n = 94); 95% confidence intervals [CIs], 65–87% and 26–51%, respectively.
• The estimated overall survival (OS) rates in the interim analysis were 94% and 83% in the Orca-T and allo-HSCT arms, respectively (95% CI, 86–97% and 73–90%; hazard ratio [HR], 0.49; p = 0.11823).
• The secondary endpoint of cumulative incidence of moderate-to-severe cGvHD was 13%  in the Orca-T arm (95% CI, 5–23%) vs 44%  in the allo-HSCT arm (95% CI, 31–56%).
• The cumulative incidence of Grade 3 or 4 GvHD was 6% in the Orca-T arm vs 17% in the allo-HSCT arms.
• The relapse-free survival rate was 76% in patients treated with Orca-T vs 74% in those who received allo-HSCT (HR, 0.80; p = 0.49).
• No new safety issues were reported with Orca-T; 6% of patients in the Orca-T arm and 10% of patients in the allo-HSCT arm experienced Grade ≥4 infections. 

Following positive results of the Precision-T study, acceptance of the Orca-T BLA marks an important clinical development for patients with AML, ALL, and MDS.