Omidubicel showed encouraging clinical benefit in a phase 3 study vs standard myeloablative umbilical cord blood in patients with blood cancers in need of an allogeneic hematopoietic stem cell transplant. Now, the FDA has approved the agent for this indication.
The FDA has granted approval to omidubicel as treatment for patients with blood cancers in need of allogeneic hematopoietic stem cell transplant (HSCT).1
This approval is supported by results from a pivotal phase 3 trial (NCT02730299). In the trial, patients treated with omidubicel had a median time to neutrophil engraftment of 12 days (95% CI, 10-14) vs 22 days (95% CI, 19-25) among patients given a standard umbilical cord blood (UCB) graft (P <.001).2
Looking at safety, differences in graft-vs-host disease (GVHD) and survival between the 2 arms were not statistically significant. The incidence of grade 2-4 acute GVHD (aGVHD) at day 100 was 56% in the omidubicel arm vs 43% in the control arm (13% difference: 95% CI, −6% to 30%; P = .18).
“With the approval of omidubicel, we have another option. We need to reconsider umbilical cord blood as a stem cell source, in the context of omidubicel, and launch studies to answer important questions as to what the benefits and the disadvantages are, and how this new stem cell product will fit in our field,” Mitchell E. Horwitz, MD, professor of medicine, director, of the Adult Blood and Marrow Transplant Program, Duke Cancer Institute, Duke University Medical Center, told Targeted OncologyTM.
Omidubicel is an advanced cell therapy candidate designed as a potential life-saving allogenic HSCT. Previously in August 2022, the FDA accepted the biologics license application for omidubicel with priority review for this patient population.
The agent was assessed in an open-label, international, multicenter, randomized, phase 3 trial compared with transplantation of 1 or 2 unmanipulated, unrelated cord blood units in patients with various blood cancers. Cancer types consisted of acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML), myelodysplastic syndrome, chronic myeloid leukemia, or lymphoma. Among all cancers, patients must have had disease features which rendered them from being eligible for allogeneic transplantation.
A total of 125 patients were enrolled and randomly assigned across 33 sites in North America, South America, Europe, and Singapore. The population of 125 randomly assigned patients was analyzed as the intent-to-treat population (ITT), using the randomized treatment assignment.
Among thepatients enrolled, 117 patients received an omidubicel or UCB transplant by day 90 after random assignment. The as-treated population consisted of 108 patients analyzed according to treatment received. Then, 52 patients were transplanted with omidubicel and 55 were transplanted with standard UCB.
Patients aged 12-65 years old with high-risk hematologic malignancies who were candidates for myeloablative allogeneic HSCT, had an available UCB unit HLA-matched at 4 or more loci with a total nucleated cell (TNC) count of 1.8 x 109 or greater, a TNC dose of 1.5 x 107cells/kg or higher, a CD34-positive cell count of 8 x 106 or more, and available backup cord blood unit were enrolled in the study.
The primary end point of the trial was median time to neutrophil engraftment, and secondary end points were the proportion of patients who achieved platelet engraftment by day 42, the proportion of patients with grade 2 or 3 bacterial or invasive fungal infections within the first 100 days after transplant, and the number of days alive and out of the hospital within the first 100 days after transplant.
Across treatment arms, patient characteristicswere well balanced. Most patients had AML (48%) or ALL (33%), and 34% of patients had a moderate disease risk index. Patients who received omidubicel underwent transplant at a median of 41 days after randomization vs 26 days among patients who received UCB. For patients treated with omidubicel, 32 patients (52%) were male vs 40 (64%) in the standard UCB arm, most patients were white (57% and 59%), and the median age of patients in the omidubicel arm was 40 (range, 13-62) vs 43 (range, 13-65) in the standard UCB arm.
Other data showed that a cumulative incidence of neutrophil engraftment by day 42 following transplantation in the omidubicel arm was 96% with a median of 10 days (95% CI, 8-13) vs 89% and with median of 20 days (95% CI, 18-24) for patients in the control arm (P < .001). For those treated with omidubicel, patients spent a median of 61 days (range, 0-89) out of the hospital in the first 100 days following transplant. In the control arm, patients spent a median of 48 days in the hospital in the first 100 days after transplant (range, 0-84). Additionally, the median time from transplant to discharge from the hospital was 27 days in the omidubicel arm vs 35 days in the control arm, respectively (P =.005).3,4
For patients in the omidubicel and control arms, the cumulative incidence of first grade 2-3 bacterial or invasive fungal infections were 37% and 57%, respectively (P = .03). The rate of first grade 3 viral infection within the first year after transplantation was 10% among those given omidubicel arm and 26% for those treated with the control, respectively (P = .02).
For safety, the rates of grade 3 to 4 aGVHD at day 100 were 14% and 21%, respectively (–7% difference; 95% CI, −21% to 7%; P =.33). Looking at the cumulative incidence of all chronic GVHD (cGVHD) at 1 year, rates were 35% with omidubicel vs 29% for the control arm (6% difference; 95% CI, −14% to 25%; P =.57). The 1-year incidence of moderate-to-severe cGVHD was 27% vs 21% (6% difference; 95% CI, −11% to 24%; P = .49) between the omidubicel and control arms.
The incidence of serious treatment-emergent adverse events possibly related to the stem cell product was 40% in the omidubicel group vs 41% in the control group. Additionally, following random assignment and prior to the start of pre transplant conditioning, 10 serious adverse events (SAEs) were reported in the omidubicel arm vs 8 SAEs in the control arm.
"Today’s approval is an important advance in cell therapy treatment in patients with blood cancers,” said Peter Marks, MD., PhD, director of the FDA’s Center for Biologics Evaluation and Research, in the press release1. “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.”