ZEMCELPRO Dispersion for infusion Ref.[116219] Active ingredients:

Pharmacotherapeutic group: Blood substitutes and perfusion solutions, other blood products
ATC code: B05AX04

Mechanism of action

Dorocubicel is a cryopreserved UM171 ((1R,4R)-N1-(2-benzyl-7-(2-methyl-2H-tetrazol-5-yl)-9H-pyrimido[4,5-b]indol-4-yl)cyclohexane-1,4-diamine dihydrobromide) expanded allogeneic hematopoietic progenitor cell therapy derived from a single cord blood unit and used as an allogeneic stem cell donor source.

The primary mechanism of action of dorocubicel lies in promoting hematopoietic recovery and immune reconstitution through the activity of expanded CD34+ hematopoietic stem cells.

The unexpanded CD34- cells, consisting primarily of CD3+ T cells, play a complementary role by supporting immune reconstitution and providing graft-versus-leukemia (GVL) effects post-transplantation.

Hematopoietic stem/progenitor cells from Zemcelpro migrate to the bone marrow where they divide, mature, and differentiate in all haematological cell lineages. The mature cells are released into the bloodstream, where some circulate and others migrate to tissue sites, partially or fully restoring blood counts and function, including immune function, of blood-borne cells of marrow origin.

Pharmacodynamic effects

Transplantation of Zemcelpro resulted in haematological reconstitution, with full donor chimerism in all hematopoietic stem cell lineages. T cell reconstitution was also prompt, with T-cell receptor (TCR) diversity at 6- and 12-months post-transplant.

Clinical efficacy and safety

The safety and efficacy of Zemcelpro treatment in patients with haematological malignancies requiring a haematopoietic stem cell transplant has been evaluated in two open label, uncontrolled, single-arm studies without comparison to other types of donor cells; in patients with high-risk leukaemia and myelodysplasia (ECT-001-CB.002 (002), n=30 and ECT-001-CB.004 (004), n=30).

The safety of Zemcelpro was also evaluated in 3 additional open label, uncontrolled, single-arm studies without comparison to other types of donor cells; (one (1) study in patients with blood cancers lacking standard HLA matched familial or unrelated donors (ECT-001-CB.001 (001); one (1) study in patients with high-risk multiple myeloma (ECT-001-CB.003 (003); n=18); one (1) study in paediatric patients with high risk myeloid malignancies (ECT-001-CB.007 (007); n=12). See section 4.8.

To assess efficacy of Zemcelpro in a representative population of adult patients with haematological malignancies requiring an allogeneic haematopoietic stem cell transplantation who lack a readily available suitable donor, pooled data from studies 002, and 004 were analysed, focusing on a pivotal population of 25 patients enrolled to receive cryopreserved Zemcelpro manufactured from a small CBU, following high or intermediate myeloablative conditioning regimen. See Table 2 for patients' characteristics. Small CB is defined as below the Be The Match & National Marrow Donor Program/American Society for Transplantation and Cellular Therapy (NMDP/ASTCT)'s minimal cell dose criteria for single CB transplant, i.e., TNC and CD34 cell content prior to cryopreservation of less than 2.5×10⁷ TNC/kg and 1.5×10 5 CD34 cells/kg, respectively.

Table 2. Pooled demographics, and baseline disease characteristics for patients in Zemcelpro Studies (at March 15, 2024):

Of the 25 patients enrolled in the pivotal population, 24 patients received infusion with Zemcelpro. Efficacy was assessed through the endpoints of neutrophil and platelet engraftment (Table 3). At data cut-off date, Studies 002 and 004 are still ongoing.

Table 3. Efficacy results in adult patients with haematological malignancies treated with cryopreserved Zemcelpro derived from small CBU (n=25), 13.3 months median follow-up:

^* All durations are reported as "time from infusion". The median duration of study enrolment to date of Zemcelpro availability at the clinical site was 31 days (IQR: 22-41 days) and median duration of study enrolment to date of Zemcelpro infusion was 42 days (IQR: 35-56 days).
^** time from infusion to date of completion or discontinuation from follow-up prior to the data cut-off
ANC: absolute neutrophil count; IQR: interquartile range
¹ Granulocyte colony-stimulating factor (G-CSF) was administered in the immediate post-transplant period (5 μg/kg/day) to minimize the risk of neutropenia and infection
² In intent-to treat populations, in a worst-case scenario analysis, patients who did not reach neutrophil engraftment by Day 42 or platelet engraftment by Day 100 post-transplant, including the patients who were not transplanted, or failed to engraft for any reason (NRM or relapse prior to engrafting) were inferred to have failed at Day 42, or Day 100, respectively.
³ Includes 1 patient who was not transplanted due to a shipment failure.

Paediatric population

The European Medicines Agency has deferred the obligation to submit the results of studies with Zemcelpro in one or more subsets of the paediatric population in HSCTs in patients with haematological malignancies (see section 4.2 for information on paediatric use).

At time of approval in adults, paediatric data is limited to 9/12 subjects less than 18 years old transplanted with Zemcelpro for high-risk myeloid malignancies in 007 study (6 with AML, 3 with MDS). Zemcelpro resulted in 88.9% and 77.8% neutrophil and platelet engraftment, respectively at a median time of 21.5 and 48 days, respectively.

This medicinal product has been authorised under a so-called 'conditional approval' scheme. This means that further evidence on this medicinal product is awaited.

The European Medicines Agency will review new information on this medicinal product at least every year and this SmPC will be updated as necessary.