The FDA has approved omidubicel-onlv (Omisirge) to quicken the recovery of neutrophils in the body and reduce the risk of infection in adults and pediatric patients aged 12 years and older with blood cancers who are slated to undergo umbilical cord blood transplantation after a myeloablative conditioning regimen.
The FDA has approved omidubicel-onlv (Omisirge) to quicken the recovery of neutrophils in the body and reduce the risk of infection in adult and pediatric patients aged 12 years and older with blood cancers who are slated to undergo umbilical cord blood transplantation after a myeloablative conditioning regimen.1
The regulatory decision was supported by findings from a randomized, multicenter, phase 3 study (NCT02730299) that compared transplantation of omidubicel with transplantation of umbilical cord blood in 125 patients with blood cancers aged 12 years to 65 years.
Eighty-seven percent of those who received omidubicel (n = 62) achieved neutrophil recovery at a median of 12 days (95% CI, 10-14) vs 83% of those who received standard UCB (n = 63) at a median of 22 days (95% CI, 19-25; P < .001).2 Moreover, at 100 days after transplantation, bacterial or fungal infections were observed in 39% of those who received omidubicel vs 60% of those who received UCB.
“Today’s approval is an important advance in cell therapy treatment in patients with blood cancers,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated in a press release. “Hastening the return of the body’s white blood cells can reduce the possibility of serious or overwhelming infection associated with stem cell transplantation. This approval reflects the FDA’s continued commitment to supporting development of innovative therapies for life-threatening cancers.”
The phase 3 study enrolled patients with hematologic malignancies who were candidates for myeloablative allogeneic allogenic hematopoietic stem cell transplant and who did not have a matched sibling or matched unrelated adult donor readily available.
To be eligible for enrollment, patients were required 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. Those who had marked or 3+ bone marrow fibrosis or chronic lymphocytic leukemia were excluded.
Fifty-two patients were transplanted with omidubicel and 55 were transplanted with standard UCB. The as-treated population included 108 patients who were evaluated according to the treatment they received; 52 of these patients were in the investigative arm and 56 were in the control arm.
Time to neutrophil engraftment served as the primary end point of the trial. Key secondary end points included time to platelet engraftment, infections by 100 days following transplant, and days alive and out of the hospital in the first 100 days following transplant.
Additional findings indicated that the cumulative incidence of neutrophil engraftment by day 42 after transplant was 96% at a median of 10 days (95% CI, 8-13) in the omidubicel arm vs 89% at a median of 20 days (95% CI, 18-24) in the control arm (P < .001).
Moreover, the cumulative incidence of platelet engraftment by day 100 after transplantation in the experimental arm was 83% at a median of 37 days (95% CI, 33-42) compared with 73% at a median of 50 days (95% CI, 42-58) for those transplanted with UCB (P = .023).
The most common adverse reactions linked with omidubicel included infections, graft-vs-host disease (GVHD), and infusion reactions. According to the FDA, those who receive the cell therapy should be monitored for signs and symptoms of the following: infusion reactions, GVHD, engraftment syndrome, graft failure, transmission of serious infections or rare genetic diseases from the donor cells, as well as life-long for secondary malignancies.1
Incidence of grade 2 to 4 acute GVHD (aGVHD) was 56% in the omidubicel arm (n = 59) vs 43% in the control arm (n = 58; 13% difference; 95% CI, -6% to 30%; P = .18).2 At day 100, grade 3/4 aGVHD was observed in 14% of patients who received omidubicel and 21% of those who received the control (-7% difference; 95% CI, -21% to 7%; P = .33).
The cumulative incidence of all aGVHD at 1 year was 35% in the investigative arm and 29% in the control arm (6% difference; 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 (6% difference; 95% CI, -11% to 24%; P = .49).
Furthermore, in the intention-to-treat population, the cumulative incidence of non-relapse mortality at 210 days after randomization was 11% with omidubicel vs 24% with standard UCB (P = .09). The cumulative incidence of disease relapse at 15 months post randomization was 25% in the investigative arm and 17% in the control arm (P = .32).
The original Prescription Drug User Fee Act date for the biologics license application seeking the approval of omidubicel was January 20, 2023.3 In November 2022, the regulatory agency extended the goal date to May 1, 2023, citing the need for additional information from Gamida Cell Ltd.4
Specifically, they requested laboratory results from intermediate time points for participants enrolled in the phase 3 trial. According to the company, the additional information provided to the FDA were consistent with previous submissions.