Pivotal phase 3 result have led the FDA to accept a biologics license applications for omidubicel as treatment of patients with blood cancers requiring allogenic hematopoietic stem cell transplant. The applications has been accepted for priority review.
The FDA has accepted the biologics license application (BLA) for omidubicel with priority review as treatment for patients with blood cancers in need of allogenic hematopoietic stem cell transplant (HSCT), according to Gamida Cell Ltd.1
The basis of the BLA comes following results from a pivotal phase 3 trial (NCT02730299) in which patients who were given omidubicel had a median time to neutrophil engraftment of 12 days (95% CI, 10-14) vs 22 days (95% CI, 19-25) in patients who received a standard umbilical cord blood (UCB) graft (P < .001).2
Omidubicel is an advanced cell therapy candidate designed as a potential life-saving allogenic HSCT. A Prescription Drug User Fee Act target action date of January 30, 2023, has been set by the FDA in order to rule on the BLA.
“The FDA’s acceptance of our BLA with priority review signifies a critical milestone in our mission to deliver a new stem cell therapy option for patients in need of a donor for an allogeneic stem cell transplant,” said Julian Adams, PhD, chief executive officer of Gamida Cell Ltd, in a press release.
In the open-label, international, multicenter, randomized, phase 3 trial, omidubicel,is being evaluated vs transplantation of 1 or 2 unmanipulated, unrelated cord blood units in patients with various blood cancers, including acute lymphoblastic leukemia or acute myeloid leukemia, myelodysplastic syndrome, chronic myeloid leukemia or lymphoma, all who which have disease features rendering them from being eligible for allogeneic transplantation.
Enrollment in the trial was open to patients aged 12 to 65 years with high-risk hematologic malignancies who were also candidates for myeloablative allogeneic HSCT.3 Patients must not have had a matched sibling or matched unrelated adult donor readily available. Additional requirements included 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 patients were also required to have available backup cord blood unit.
The study enrolled and randomly assigned 125 patients at 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, and of the 125, 117 patients received an omidubicel or UCB transplant by day 90 after random assignment. The as-treated population included 108 patients analyzed according to treatment received.
Of those enrolled, 52 patients were transplanted with omidubicel and 55 with standard UCB. The primary end point of the trial was median time to neutrophil engraftment with secondary end points including 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.
Patient characteristics were well balanced across the treatment arms with the majority of patients having acute myeloid leukemia (48%) or acute lymphoblastic leukemia (33%). Additionally, 34% of patients had a moderate disease risk index. Patients treated with omidubicel underwent transplant at a median of 41 days following randomization compared with 26 days for those who received UCB. In the omidubicel arm, 32 patients (52%) were male vs 40 (64%) in the standard UCB arm. A majority of patients were white (57% and 59%), and the median age of patients who received omidubicel was 40 (range, 13-62) and 43 (range, 13-65) for those who were transplanted with standard UCB.
Additional data showed that the cumulative incidence of neutrophil engraftment by day 42 following transplantation for patients who received omidubicel was 96% with a median of 10 days (95% CI, 8-13) compared with 89% and with median of 20 days (95% CI, 18-24) for patients in the control arm (P < .001).
In the omidubicel arm, patients spent a median of 61 days (range, 0-89) out of the hospital in the first 100 days following transplant while those in the control arm spent a median of 48 days (range, 0-84). The median time from transplant to discharge from the hospital was 27 days compared with 35 days in the omidubicel and control arms, respectively (P = .005).
The cumulative incidence of first grade 2 to 3 bacterial or invasive fungal infections was 37% and 57% for patients in the omidubicel and control groups, respectively (P = .03), and the rate of first grade 3 viral infection within the first year after transplantation was 10% in the omidubicel arm and 26% in the control group, respectively (P = .02).
In regard to safety, differences in graft-vs-host disease (GVHD) and survival between the 2 arms were not statistically significant with the incidence of grade 2 to 4 acute GVHD (aGVHD) at day 100 being 56% in the omidubicel arm compared with 43% in the control arm (13% difference: 95% CI, −6% to 30%; P = .18). At day 100, 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). The cumulative incidence of all chronic GVHD (cGVHD) at 1 year was 35% for the omidubicel arm vs 29% for the control arm (6% difference; 95% CI, −14% to 25%; P = .57). Further, the 1-year incidence of moderate-to-severe cGVHD was 27% and 21% (6% difference; 95% CI, −11% to 24%; P = .49).
Additionally, the incidence of serious treatment-emergent adverse effects which were possibly related to the stem cell product was 40% in the omidubicel group compared with 41% in the control group. After random assignment and before starting pre transplant conditioning, there were 10 serious adverse events (SAEs) reported for those in the omidubicel arm and 8 SAEs reported for those in the control arm.
“We are encouraged by the positive and sustained follow-up results from patients participating in the phase 3 trial of omidubicel, including a positive overall survival trend one-year out from treatment,” added Adams. “These results provide promising rationale that, if approved, omidubicel could become a treatment of choice for patients in need of an [allogenic] HSCT transplant. We look forward to working with the FDA throughout the review process to bring omidubicel to patients as quickly as possible.”