The FDA has granted approval to omidubicel for the treatment of patients with blood cancers who are in need of allogeneic hematopoietic stem cell transplant (HSCT). This approval marks a significant advancement in cell therapy, offering a new option to patients who may not be eligible for traditional transplant methods.
The approval is based on the results of a pivotal phase 3 trial (NCT02730299) that compared omidubicel to standard umbilical cord blood (UCB) grafts. The study, which enrolled 125 patients across multiple sites in North America, South America, Europe, and Singapore, demonstrated a significant reduction in the median time to neutrophil engraftment with omidubicel. Patients treated with omidubicel experienced a median time to neutrophil engraftment of 12 days (95% CI, 10-14) compared to 22 days (95% CI, 19-25) in the standard UCB graft arm (P < .001).
Clinical Trial Details
The phase 3 trial was an open-label, international, multicenter, randomized study. It enrolled patients aged 12-65 years with high-risk hematologic malignancies, including acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic syndrome, chronic myeloid leukemia, or lymphoma, who were candidates for myeloablative allogeneic HSCT. Patients were required to have an available UCB unit HLA-matched at 4 or more loci.
The primary endpoint of the trial was the median time to neutrophil engraftment. Secondary endpoints included 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.
Efficacy and Safety
In addition to faster neutrophil engraftment, the trial data revealed that the cumulative incidence of neutrophil engraftment by day 42 was 96% in the omidubicel arm, with a median of 10 days (95% CI, 8-13), compared to 89% in the control arm, with a median of 20 days (95% CI, 18-24) (P < .001). Patients treated with omidubicel also spent a median of 61 days (range, 0-89) out of the hospital in the first 100 days following transplant, compared to 48 days (range, 0-84) in the control arm. The median time from transplant to discharge from the hospital was 27 days in the omidubicel arm versus 35 days in the control arm (P = .005).
Regarding safety, the rates of grade 3 to 4 acute GVHD (aGVHD) at day 100 were 14% and 21% in the omidubicel and control arms, respectively (P = .33). The cumulative incidence of all chronic GVHD (cGVHD) at 1 year was 35% with omidubicel versus 29% for the control arm (P = .57).
Expert Commentary
Dr. Mitchell E. Horwitz, MD, professor of medicine and director of the Adult Blood and Marrow Transplant Program at Duke Cancer Institute, commented on the approval, stating, "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."
Implications for Treatment
The FDA's approval of omidubicel represents a significant step forward in the treatment of blood cancers. By hastening the return of white blood cells, omidubicel can reduce the risk of serious infections associated with stem cell transplantation. This approval underscores the FDA’s commitment to supporting the development of innovative therapies for life-threatening cancers and provides a valuable new option for patients in need of HSCT.
