Omidubicel

There are no available data with omidubicel use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with omidubicel to assess whether it can cause fetal harm when administered to a pregnant woman. In Study 17-H-0091, one patient reported two pregnancies, one at 9 months and one at 3.5 years post-transplant. There were no reported birth complications or neonatal concerns.

Omidubicel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

In the United States (U.S.) general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

There is no information regarding the presence of omidubicel in human milk, the effect on the breastfed infant, and the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for omidubicel and any potential adverse effects on the breastfed infant from omidubicel or from the underlying maternal condition.

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

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Hematologic Malignancies

The safety of omidubicel is based on data from Study P0501 for 52 patients transplanted with omidubicel and 56 patients transplanted with umbilical cord blood (UCB). The median duration of follow up for the overall safety population was 14 months (range, 1-19 months). All patients received myeloablative preparative regimens and GvHD prophylaxis with tacrolimus or cyclosporin plus mycophenolate mofetil.

Fatal adverse reactions occurred in 17% of patients treated with omidubicel, including infection (6%), acute GvHD (6%), veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) (2%), thrombotic thrombocytopenic purpura (TTP)/thrombotic microangiopathy (TMA) (2%), and pulmonary hemorrhage (2%). Fatal adverse reactions occurred in 29% of subjects treated with UCB, including infection/sepsis (11%), respiratory disorders (11%), GvHD (5%), and VOD/SOS (2%).

The most common non-laboratory adverse reactions occurring in ≥10% of patients in Study P0501 are listed in Table 1 below. The most common Grade 3-5 adverse reactions for patients treated with omidubicel, were pain (33%), mucosal inflammation (31%), hypertension (25%), and gastrointestinal toxicity (19%).

Table 1. Adverse Reactions in ≥10% of Patients with Hematologic Malignancies Following Transplantation with Omidubicel (N-52) or UCB (N=56) in Study P0501:

Abbreviation: CTCAE: common terminology criteria for adverse events; n: number; UCB: umbilical cord blood.
^* Fatigue includes asthenia and fatigue
^† Infections and infestations were graded according to the BMT-CTN grading system
^‡ Acute Graft-versus-host disease was graded according to the Consensus Conference on Acute GvHD grading
^§ Chronic Graft-versus-host disease was graded according to the 2014 NIH consensus criteria
^¶ Hemorrhage include cystitis hemorrhagic, epistaxis, gastrointestinal hemorrhage, hemorrhage, pulmonary alveolar hemorrhage, subarachnoid hemorrhage, and upper gastrointestinal hemorrhage
^# Respiratory failure includes acute respiratory distress syndrome, acute respiratory failure, hypoxia, and respiratory failure
^Þ Renal impairment includes acute kidney injury, blood creatinine increased and renal failure

Table 2 summarizes selected chemistry abnormalities by treatment arm for patients treated in Study P0501.

Table 2. Chemistry Laboratory Abnormalities in ≥10% of Patients in Study P0501:

Abbreviation: N: number; UCB: umbilical cord blood.

Severe Aplastic Anemia

The safety data described in this section reflects exposure of omidubicel in one clinical study (Study 17-H-0091) for the treatment of severe aplastic anemia (SAA). A total of 17 patients received a single dose of omidubicel with a median dose of 8.5 × 10⁶ cells/kg CD34+ cells (range, 2.3-21.4 cells/kg CD34+ cells). Three out of 17 patients received omidubicel with haploidentical CD34+ cells. All patients received a reduced intensity preparative conditioning regimen of cyclophosphamide, fludarabine, TBI and horse-ATG, and GvHD prophylaxis according to institutional guidelines. The median duration of follow-up was 25 months (range, 2-60 months).

Serious adverse reactions were reported in 15 patients including infections (n=15), diarrhea (n=3), nausea/vomiting (n=4), pyrexia (n=2), hypoxia (n=2), thrombotic microangiopathy (n=1), cardiac arrest (n=1), pericarditis (n=1), colitis (n=1), febrile neutropenia (n=1), cholecystitis (n=1), portal vein thrombosis (n=1), graft versus host disease (n=1), weight decreased (n=1), dehydration (n=1), Guillain-Barre Syndrome (n=1), uterine hemorrhage (n=1), pleural effusion (n=1), pulmonary hemorrhage (n=1), and respiratory failure (n=1).

One patient (6%) treated with omidubicel had a fatal adverse event. The patient engrafted but died on Day 62 from disseminated adenovirus infection.

The most common adverse reactions occurring in ≥15% of patients in Study 17-H-0091 are listed in Table 3 below.

CTCAE Grade 3-5 non-laboratory adverse reactions in the SAA Study with greater or equal to 15% incidence are summarized in Table 3. The most common Grade 3-5 adverse reactions for patients treated with omidubicel were febrile neutropenia (41%), bacterial infections (41%), hyperglycemia (41%), Epstein-Barr virus infection (29%), immune thrombocytopenia (24%) and pneumonia (24%).

Table 3. Adverse Reactions in ≥15% of Patients with SAA Following Transplantation with Omidubicel (N=17) in Study 17-H-0091:

Abbreviation: n: number.
^* Includes skin infection, clostridium difficile infection, device related infections and urinary tract infections.
^† Is a composite that includes multiple related terms.
^‡ Includes hypertension, headache and hypoxia.
^§ Includes dyspnea, respiratory distress and respiratory failure.

Other clinically significant adverse reactions occurring in <15% of patients include the following: Post-transplant lymphoproliferative disorder in two patients (12%), primary graft failure (defined as failure to achieve an absolute neutrophil count ≥500 cells/µl for 3 consecutive measurements on different days) in 1 patient (6%), and engraftment syndrome in 1 patient (6%).

Table 4 summarizes laboratory abnormalities that worsened from baseline in ≥15% of patients in Study 17-H-0091.

Table 4. Laboratory Abnormalities that Worsened from Baseline in ≥15% of Patients in Study 17-H-0091 (N=17):

Abbreviation: N: number.