The FDA has extended the PDUFA date for the Orca-T BLA to July 6, 2026.
The FDA has extended its review period of the biologics license application (BLA) seeking the approval of Orca-T for the treatment of patients with hematologic malignancies.1
After the FDA
Notably, no additional clinical data were requested by the FDA. Orca Bio—the developer of Orca-T—noted in a news release that the amendment does not appear to affect the risk-benefit conclusion of the application.
"We appreciate the frequent engagement with the FDA throughout the review process,” Nate Fernhoff, cofounder and chief executive officer at Orca Bio, stated in a news release. “Our continued focus is on preparing for the potential approval and commercial launch of Orca-T. We remain committed to working with the agency, physicians, and the broader blood cancer community to deliver this important therapy to patients with hematologic malignancies as quickly as possible.”
The BLA was backed by data from the phase 3 Precision-T trial (NCT04013685), where Orca-T generated a statistically significant improvement in moderate to severe chronic graft-vs-host disease (cGVHD)–free survival compared with conventional allogeneic hematopoietic stem cell transplant (allo-HSCT) in patients with hematologic malignancies, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndromes (MDS).3
Findings showed that patients treated with Orca-T (n = 93) achieved a 1-year moderate to severe cGVHD-free survival rate of 78% (95% CI, 65%-87%) compared with 38% (95% CI, 26%-51%) for patients treated with conventional allo-HSCT (HR, 0.26; P < .00001).2 Overall, moderate-to-severe cGVHD occurred in 13% (95% CI, 5%-23%) of patients in the Orca-T arm vs 44% (95% CI, 31%-56%) of those in the allo-HSCT group (HR, 0.19; P < .00002).
Patients in the Orca-T arm also experienced a 1-year overall survival (OS) rate of 94% (95% CI, 86%-97%) compared with 83% (95% CI, 73%-90%) for those in the allo-HSCT arm (HR, 0.49; P = .11823).
Furthermore, the 1-year relapse-free survival rate was 76% for Orca-T vs 74% in the allo-HSCT arm (HR, 0.80; P = .49). Nonrelapse mortality was reported in 3% of patients treated with Orca-T vs 13% of those given allo-HSCT. Grade 3/4 acute GVHD occurred at respective rates of 6% and 17%.
No new safety signals were reported with Orca-T. The rates of grade 4 or higher infections were 6% for patients in the Orca-T arm vs 10% for patients in the allo-HSCT arm.
Investigators of the open-label, randomized, multicenter, phase 3 study enrolled patients 18 to 65 years of age with acute leukemia in complete remission (CR) or CR with incomplete hematologic recovery; or with MDS indicated for allo-HSCT per 2017 International Expert Panel recommendations and/or therapy-related/secondary MDS, with no more than 10% bone marrow blasts.4 Planned administration of a matched related or unrelated donor allo-HSCT with total body irradiation (TBI) and cyclophosphamide; TBI and etoposide; or busulfan, fludarabine, and thiotepa was required.
Patients also needed to have a resting cardiac ejection fraction of at least 45% or a shortening fraction of at least 27%; alanine aminotransferase and aspartate aminotransferase levels less than 3 times the upper level of normal (ULN); intermediate- or high-risk disease designation; and a total bilirubin level less than the ULN.
Those who underwent prior allo-HSCT were excluded from the study.
Investigators randomly assigned patients to receive Orca-T plus single-agent tacrolimus, or allo-HSCT plus tacrolimus and methotrexate.2 In both arms, patients underwent myeloablative conditioning and used a related or unrelated matched donor.
Moderate to severe cGVHD-free survival at 1 year served as the trial’s primary end point. Secondary end points included time to moderate to severe cGVHD, OS, and the rate of patients free from both cGVHD and relapse at 1 year.4
