Of two ASH-FDA Joint Symposia at this year’s annual American Society of Hematology meeting, we focus on discussion of the late-breaking approval on December 5 of omidubicel, the first modified cord blood-based cell therapy approved for severe aplastic anemia. Omidubicel was previously approved for hematologic malignancies, and the new indication addresses an unmet need for patients without matched sibling donors. Megha Kaushal, MD, acting deputy director Office of Therapeutic Products, Center for Biologics Evaluation and Research, FDA, presented key safety and efficacy data leading to this new indication.
Allogeneic hematopoietic stem cell transplantation is the only potential curative therapy for many hematologic diseases, but many patients struggle to find a matched donor. Umbilical cord blood transplant has advantages over unrelated donor transplant, including less stringent matching requirements leading to a greater probability for finding a matched donor.
Omidubicel addresses a limitation of umbilical cord blood transplantation, namely the low number of hematopoietic stem cells per unit, which leads to prolonged time to engraftment and a higher rate of post-transplant complications, including infections, longer hospitalization, and increased transplant-related mortality.
Omidubicel is a patient-specific, nicotinamide modified allogeneic hematopoietic progenitor cell therapy derived from a single banked umbilical cord blood unit, manufactured by culturing CD133 positive cells with cytokines in the presence of nicotinamide producing enriched hematopoietic stem and progenitor cells. Two fractions, administered sequentially, include cultured, ex vivo expanded hematopoietic CD34 positive progenitor cells, and non-cultured hematopoietic mature myeloid and lymphoid cells.
Evaluation was based on the interim analysis of 14 patients from the ongoing study 17-H-0091 (NCT03173937). Dr. Kaushal noted most patients were non-white, a population known to be underrepresented in the unrelated donor and umbilical cord registries. The primary efficacy objective was met with neutrophil recovery in 12 of 14 patients by day 42, with median day to engraftment of 11 days (range 7 to 20 days).
Key secondary efficacy outcomes included red blood cell transfusion independence (12 of 14 patients, median 58.5 days), platelet recovery of over 20,000 (12 of 14 patients (median time to recovery 31.5 days), and platelet transfusion independence (11 of 14 patients, median time 53 days).
Safety data included 1 death attributed to adenovirus; 4 patients with acute grade 1 or 2 graft versus host disease; and 4 with autoimmune cytopenias, mostly in pediatric patients, requiring a box warning, and administration to those age ≥6 years.
Clinical discussant Larisa Broglie, MD, said finding a well-matched unrelated donor in the registry varies greatly based on a patient’s underlying race and ethnicity, and that those in radical or ethnic minorities are unlikely to find a well-matched donor. She said that with the approval of omidubicel, “Ultimately we can now confidently say that all patients who need a transplant will have a donor for transplant, and donor availability no longer limits transplant access for patients with aplastic anemia. Physicians can look at multiple donor options, including haploidentical donors, matched and mismatched unrelated donors, and now expanded cord blood, to choose the donor that is best for each patient.”
Dr. Lederman has no conflicts of interest to report.
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