On April 17, 2023, the FDA approved omidubicel-onlv (Omisirge; Gamida Cell), a substantially modified allogeneic cord blood–based cell therapy, for use in adults and pediatric patients aged ≥12 years with hematologic malignancies who are to receive umbilical cord blood transplant after myeloablative conditioning to reduce the time to neutrophil recovery and the incidence of infection. The FDA granted this approval priority review and breakthrough and orphan drug designations.
“The approval of Omisirge is a significant development in hematopoietic stem-cell transplantation,” said Steven M. Devine, MD, Chief Medical Officer of the National Marrow Donor Program/Be The Match. “Adding Omisirge as a new donor source may help increase access to stem-cell transplant for patients from racially or ethnically diverse backgrounds who struggle to find a fully matched donor in the registry.”
This approval is based on data from the pivotal Study P0501 (NCT02730299), an open-label, multicenter, international, randomized, phase 3 clinical trial that compared 125 patients with hematologic malignancies who received omidubicel or standard unmanipulated cord blood transplant (UCBT) after myeloablative conditioning and prophylaxis with a calcineurin inhibitor and mycophenolate mofetil for graft-versus-host disease (GVHD).
In all, 62 of the study patients were randomized to receive omidubicel and 63 to receive UCBT. A total of 52 patients received omidubicel, with a median CD34+ cell dose of 9 × 106 cells/kg (range, 2.1-47.6 × 106 cells/kg). In the UCBT arm, 56 patients received 1 or 2 units of unmanipulated cord blood (66% received 2 units). In the 42 patients who had a postthaw cell dose, the median CD34+ cell dose was 0.2 × 106 cells/kg (range, 0.0-0.8 × 106 cells/kg). Total body irradiation–based and chemotherapy-based regimens were among the many conditioning regimens used in the study.
The major efficacy measures included time to neutrophil recovery after transplant and the incidence of grade 2 or 3 bacterial infections or grade 3 fungal infections through 100 days after transplant. The median time to neutrophil recovery was 12 days in the omidubicel group (95% confidence interval [CI], 10-15 days) and 22 days in the UCBT group (95% CI, 19-25 days). In the omidubicel and UCBT arms, 87% and 83% of patients, respectively, achieved neutrophil recovery. The incidences of grade 2 or 3 bacterial infections or grade 3 fungal infections through 100 days after transplant were 39% and 60%, respectively, in the 2 groups.
Omidubicel’s prescribing information has a boxed warning for fatal or life-threatening infusion reactions, GVHD, engraftment syndrome, and graft failure. In 117 study patients who received omidubicel for the treatment of any disease, 47% had infusion reactions, 58% had acute GVHD, 35% had chronic GVHD, and 3% had graft failure.
In this study, the most common grade 3 to 5 adverse reactions in patients with hematologic malignancies were pain (33%), mucosal inflammation (31%), hypertension (25%), and gastrointestinal toxicity (19%).
The recommended dose of omidubicel is a cultured fraction, which consists of a minimum of 8 × 108 total viable cells with a minimum of 8.7% CD34+ cells and a minimum of 9.2 × 107 total CD34+ cells, followed by a noncultured fraction that consists of a minimum of 4.0 × 108 total viable cells with a minimum of 2.4 × 107 CD3+ cells.