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The rolling biologics license application submission to the FDA to support the approval of omidubicel for patients with blood cancers in need of allogenic hematopoietic stem cell transplant has been completed.
The rolling biologics license application (BLA) submission to the FDA to support the approval of omidubicel for patients with blood cancers in need of allogenic hematopoietic stem cell transplant (HSCT) has been completed, according to an announcement from Gamida Cell Ltd.1
The application is supported by data from a phase 3 trial (NCT02730299), which showed that the use of omidubicel in patients with hematologic malignancies who were undergoing allogeneic bone marrow transplant experienced a shorter median time to neutrophil engraftment than those who were transplanted with standard umbilical cord blood (UCB), at 12 days (95% CI, 10-14) vs 22 days (95% CI, 19-25; P < .001).2
Fifty-five percent of those who received omidubicel achieved platelet engraftment by day 42 following transplantation vs 35% of those who received standard treatment (P = .028). Moreover, those in the investigative arm experienced a significant reduction in the cumulative incidence of first grade 2 or 3 bacterial or invasive fungal infections vs those in the control arm, at 37% and 57%, respectively (P = .03).
Hospitalization in the first 100 days following transplant was also reduced in those who received omidubicel. Specifically, the median number of days alive and out of the hospital for those in the investigative and control arms was 61 days and 48 days, respectively (P = .005).
“The BLA submission marks an important milestone for both Gamida and the transplant community, as omidubicel has the potential to be the first approved advanced cell therapy product for allogeneic stem cell transplantation,” Julian Adams, PhD, chief executive officer of Gamida Cell, stated in a press release.
The trial enrolled those with hematologic malignancies who were between the ages of 12 years and 65 years and who were candidates for myeloablative allogeneic HSCT who did not have a matched sibling or matched unrelated adult donor readily available.
To be eligible for enrollment, patients needed to have an available UCB unit HLA-matched at 4 or more loci with a total nucleated cell (TNC) count of 1.8 x 109 or higher, a TNC dose of 1.5 x 107 cells/kg, and a CD34-positive cell count of 8 x 106 or higher. If patients had marked or 3+ bone marrow fibrosis or chronic lymphocytic leukemia, they were excluded from the research.
The intention-to-treat population was comprised of a total of 125 patients who were randomized to the omidubicel arm (n = 62) or with standard cord arm (n = 63). Of these patients, 52 were transplanted with omidubicel in accordance with trial protocol and 55 were transplanted with standard cord. The as-treated population included 108 patients who were assessed according to the treatment they received; 52 were in the investigative arm and 56 were in the control arm.
Cord blood units were selected before randomization, and this was stratified by treatment center, disease risk index, age, and intent to perform single vs double cord transplant in the control arm.
The primary end point of the trial was time to neutrophil engraftment, and key secondary end points included time to platelet engraftment, infections by 100 days following transplant, and hospitalizations, which was defined as the days alive and out of the hospital in the first 100 days following transplant.
Demographic and baseline characteristics were noted to be well balanced across the treatment arms. The majority of patients had acute myeloid leukemia (48%) or acute lymphoblastic leukemia (33%). Moreover, 34% of patients had a moderate disease risk index. Those who received omidubicel underwent transplant at a median of 41 days following randomization vs 26 days for those who received UCB.
Additional data showed that the cumulative incidence of neutrophil engraftment by day 42 following transplant in the investigative and control arms was 96% at a median of 10 days (95% CI, 8-13) vs 89% at a median of 20 days (95% CI, 18-24), respectively (P < .001). Moreover, among those who were transplanted with omidubicel, higher total CD34-positive cell counts and CD34-positive cell doses were linked with reduced time to neutrophil engraftment.
Moreover, the cumulative incidence of platelet engraftment by day 100 following transplantation was 83% at a median of 37 days (95% CI, 33-42) among those transplanted with omidubicel compared with 73% at a median of 50 days (95% CI, 42-58) in those transplanted with UCB (P = .023).
Incidence of grade 2 to 4 acute graft-vs-host (aGVHD) was similar between the investigative (n = 59) and control (n = 58) arms, at 56% and 43%, respectively (95% CI, -6% to 30%; P = .18). At day 100, grade 3 to 4 aGVHD occurred in 14% of those in the investigative arm and 21% of those in the control arm, translating to a difference of -7% (95% CI, -21% to 7%; P = .33).
At 1 year, the cumulative incidence of all aGVHD was 35% and 29%, respectively (95% CI, -14% to 25%; P = .57). The 1-year cumulative incidence of moderate to severe chronic GVHD in the investigative and control arms was 27% and 21%, respectively (95% CI, -11% to 24%; P = .49).
In the ITT population, the cumulative incidence of non-relapse mortality at 210 days following randomization was 11% and 24% in the investigative and control arms, respectively (P = .09). Furthermore, the cumulative incidence of disease relapse at 15 months following randomization was 25% and 17%, respectively (P = .32).
In November 2021, Gamida Cell Ltd., the manufacturer of the advanced cell therapy, completed a Type B Pre-BLA meeting with the FDA to discuss omidubicel as a potential therapeutic option for this patient population.3
In the meeting, the regulatory agency requested that the company provide a revised analysis of the manufacturing information that was produced by the company’s commercial manufacturing facility to demonstrate how it compares with how the product was produced at manufacturing sites used for the phase 3 trial. Additional clinical data to initiate the submission of the application had not been requested.
“Completion of this BLA submission is a key inflection point in our mission to deliver a new treatment option for patients with blood cancers,” Adams added in the release. “We look forward to working closely with the FDA to bring this potentially important therapy to patients.”