Stemex® Is Expanding: Pivotal Trial Nears Completion, and Development of a Cryopreserved Product Is Underway

Cord blood transplantation (CBT) is limited by low number of TNC and CD34+ cells, influencing the incidence and rate of hematopoietic recovery and risk of early transplant-related mortality. Ex vivo expansion is a strategy to increase the number of progenitor cells and improve clinical outcomes. Several early stage studies are evaluating the clinical benefit of expansion, mainly in a double CBT configuration. The StemEx® trial evaluates the potential contribution of expansion in a single CBT configuration. StemEx is manufactured from a portion of a single CBU, originally frozen in 2 separate fractions. CD133+ progenitor cells, purified from the smaller or equal fraction, are cultured for 21-23 days with cytokines and a copper chelator, TEPA, which delays differentiation and promotes expansion of progenitor cells with engraftment capabilities. A global pivotal registration study evaluating the safety and efficacy of StemEx in patients with hematological malignancies following myeloablative treatment is currently completing recruitment. Safety and efficacy outcomes of the study will be available in 2012. To date, 82 of 88 StemEx batches manufactured in 3 centralized GMP facilities, have been successfully expanded: median fold expansion of TNC, CD34+ cells and CFU over culture input were 399 (range 52-764), 75 (6-280) and 107 (43-662), respectively. Expansion of only a portion of the CBU resulted in a median 8.4 fold increase (0.8-90.3) in the number of CD34+ cells infused over the number that would be infused from the entire CBU without expansion. The CFU potential of culture seeded CD133+ cells measured at day-0 of production indicates the expansion potential of the cryopreserved CB cells. In all six batches which failed to expand, day-0 CFU was low, while day-0 CFU of all successfully expanded batches was within specification ranges. This information, available before patient myeloablation, strengthens the clinical applicability of StemEx. All StemEx batches were successfully delivered and infused. We are currently in the last stages of development of a frozen StemEx product. The added flexibility in the timing of transplantation allows for changes resulting from patient disease progression or complications. With the challenges of an ex vivo expanded product being successfully met in the current registration trial, and the development of a frozen product, StemEx demonstrates its feasibility as a quality alternative stem cell source for allogeneic HSCT.