OMISIRGE Suspension for solution for infusion Ref.[116107] Active ingredients: Omidubicel

Transplantation with OMISIRGE resulted in rapid and broad immune reconstitution of dendritic cells, monocytes, Natural Killer (NK), CD4+ T cells and CD8+ T cells as early as one-week post-transplantation, and B cells 28 days post transplantation and all lineages throughout the one-year follow-up period. Robust positive linear correlations between the CD34( + ) cell content in the OMISIRGE CF, and the reconstitution of T-cells and NK cells were identified. Additionally, dose-response analyses demonstrated a strong correlation between the total CD34+ cell counts and dose/kg for OMISIRGE with the kinetics of neutrophil recovery. The model demonstrated that days to neutrophil recovery decreased with an increase in OMISIRGE CD34( + ) cell dose.

OMISIRGE is a cryopreserved nicotinamide modified allogeneic hematopoietic progenitor cell therapy derived from cord blood. The nature of OMISIRGE is such that conventional pharmacokinetic studies on absorption, distribution, metabolism, and excretion are not applicable.

No in vivo carcinogenicity, mutagenicity and fertility studies were conducted to evaluate the effects of OMISIRGE.

14.1 Hematologic Malignancies

OMISIRGE was evaluated in Study P0501 (NCT02730299), an open-label, multicenter, randomized study of OMISIRGE transplantation or UCB transplantation following myeloablative conditioning in patients with hematologic malignancies.

In total, 125 patients with the availability of at least one ≥4/6 human leukocyte antigen (HLA)-matched (HLA-A, B and DR loci) cord blood unit were randomized to the study, 62 patients were randomized to receive OMISIRGE and 63 patients were randomized to the UCB group. The minimum specifications of OMISIRGE were a Total Nucleated Viable Cell (TNVC) count of 8.0 × 10⁸ cells and CD34+ cell count of 5.6 × 10⁷. Fifty-two patients were transplanted with OMISIRGE at a median CD34+ cell dose of 9.0 × 10⁶ cells/kg (range 2.1-47.6 × 10⁶ cells/kg). Fifty-six patients were transplanted in the UCB arm with one or two cord units (66% received two cord units); among patients in whom the post-thaw cell dose was reported (n=42), the median CD34+ cell dose was 0.2 × 10⁶ cells/kg (range 0.0-0.8 × 10⁶ cells/kg). Multiple conditioning regimens were used, including Total Body Irradiation (TBI)-based or chemotherapy-based options.

Demographic and baseline patient characteristics were similarly distributed among the treatment arms. The overall study population included 72 males (58%) and 53 females (42%) with median age 41 years (range: 13–65). Fifty-eight percent of patients were White, 16% were Black, 14% were Asian and 13% were of other races or unknown. Thirteen percent of patients identified as Hispanic or Latino. Forty-eight percent of patients had Acute Myelogenous Leukemia (AML), 33% had Acute Lymphoblastic Leukemia (ALL), 7% had Myelodysplastic Syndrome (MDS), 5% had Chronic myeloid leukemia (CML), 4% had lymphoma and 3% had other rare leukemias. Baseline disease status (remission vs. overt disease) varied depending on the hematologic malignancy. Disease risk index was high/very high for 34% and moderate for 42%. HCT specific comorbidity index was ≥3 in 51% and 1-2 in 28% of patients.

Of the patients randomized to OMISIRGE, 8% of patients (5/62) were not able to receive OMISIRGE due to manufacturing failure.

The efficacy of OMISIRGE was established based on time to neutrophil recovery following transplantation and the incidence of BMT CTN Grade ⅔ bacterial or Grade 3 fungal infections through Day 100 following transplantation. The efficacy outcomes are summarized below.

Table 6. Efficacy Results in Patients Randomized to Receive OMISIRGE or UCB in Study P0501 (ITT Population):

Abbreviation: CI: Confidence interval; N: number; UCB: umbilical cord blood.
^* Time to neutrophil recovery was defined as the time from transplantation to the earliest of 3 consecutive measurements on different days with absolute neutrophil count greater than or equal to 0.5 Gi/L assessed with 42 days of follow-up.
^† Median time to neutrophil recovery was estimated by the Kaplan-Meier estimator.

Eighty-seven percent of patients in the OMISIRGE arm and 83% in the UCB arm achieved neutrophil recovery. The median time to neutrophil recovery was 12 days in the OMISIRGE arm and 22 days in the UCB arm. BMT CTN Grade ⅔ bacterial or Grade 3 fungal infections through Day 100 following transplantation occurred in 39% of patients in the OMISIRGE arm and 60% of patients in the UCB arm.

Per Protocol Population

Among the patients treated with OMISIRGE (n=52), neutrophil recovery with 42 days of follow-up was achieved in 94% of patients at a median of 10 days (95% CI: 8, 12), compared to 89% of patients treated with UCB (n=56), at a median of 20 days (95% CI: 18, 24). BMT CTN Grade ⅔ bacterial or Grade 3 fungal infections by 100 days were reported in 35% of patients treated with OMISIRGE and 61% of patients treated with UCB, respectively.

14.2 Severe Aplastic Anemia

The efficacy of OMISIRGE in patients with severe aplastic anemia (SAA) was evaluated in study 17- H-0091 (NCT 03173937), an open-label, single center study. The study enrolled patients with SAA who had intolerance or failure to respond to immunosuppressive therapy and availability of at least one ≥4/8 human leukocyte antigen (HLA)-matched (HLA-A, B, C and DR loci) cord blood unit. Patients were excluded if there was availability of an HLA identical (12/12) matched related or unrelated donor.

In total, 17 patients were treated with OMISIRGE, among them 14 patients were treated with OMISIRGE alone and three patients were treated with both OMISIRGE and haploidentical CD34+ cells. The minimum specifications of OMISIRGE were a Total Nucleated Viable Cell (TNVC) count of 8.0 × 10⁸ cells and CD34+ cell count of 9.2 × 10⁷. The fourteen patients who were transplanted with OMISIRGE alone were included in the efficacy evaluation. The median CD34+ cell dose of OMISIRGE was 9.5 ×10 ⁶ cells/kg (range, 2.3-21.4 cells/kg). All patients received reduced intensity conditioning which included cyclophosphamide, fludarabine, TBI and horse-ATG. GvHD prophylaxis was administered according to institutional guidelines.

The demographic characteristic of the population included the following: median age was 17 years (range: 6-45), 10 patients (59%) were male, 6 patients (35%) were Black, 3 patients (18%) were White, 5 patients (29%) were Asian and 3 patients (18%) were of "other races" or "unknown". Twenty-nine percent of patients identified as Hispanic or Latino. Median absolute neutrophil count at baseline was 0.3 × 10⁹/L (range, 0.0-1.0) and median platelet count at baseline was 35 × 10⁹/L (range, 10-89). Hematopoietic stem cell transplantation (HCT) specific comorbidity index was ≥3 in 76% and 0-2 in 24% of patients. Twelve percent of patients received 4/8 HLA match, 59% 5/8 HLA match, 18% 6/8 HLA match, 6% 7/8 HLA match and 6% 8/8 HLA match.

The primary efficacy outcome measure was the incidence of early and sustained neutrophil recovery, defined as ANC ≥500 cells/µl for 3 consecutive measurements on different days by Day 26, maintained at Days 42 and 100 posttransplant. Other secondary efficacy outcomes were neutrophil recovery (days to first of three consecutive ANC≥500 cells/µL), red blood cell (RBC) transfusion independence (days to 30-day transfusion independence), platelet recovery ≥20,000/µL (days to first of 3 consecutive platelet count of 20,000/µL with no preceding transfusion in 7 days) and platelet transfusion independence (days to 30-day platelet transfusion independence).

The efficacy results are summarized in Table 7 below.

Table 7. Efficacy Results from Study 17-H-0091:

Abbreviation: CI: Confidence interval; min: Minimum; max: Maximum; N: number.
^* 95% CI was calculated by the Clopper-Pearson method.
^† Time to neutrophil recovery was defined as ANC ≥500 cells/μl for 3 consecutive measurements on different days.
^‡ Based on patients who achieved the events.