omidubicel-onlv

Action and Spectrum

Actions and Spectrum:

omidubicel has been shown to have a broad spectrum of activity, potentially benefiting patients with a wide range of hematologic malignancies who have undergone BMT. Additionally, because omidubicel can be manufactured in advance of the patient’s transplant, it can be immediately available for infusion when needed, which can reduce the time to engraftment (the point at which the donor cells start to produce new blood cells) and shorten the length of hospital stays for patients.

Drug Interaction

Adverse Reaction

Frequency defined

>10%

Viral infections, Grade 1-3 (75%)

Decreased Magnesium, Grade 1-4 (94%)

Chronic GVHD (35%)

Enhanced Alkaline phosphatase, Grade 1-4 (42%)

Pain (33%)

Respiratory failure (12%)

Hypertension (25%)

Fungal infections, Grade 1-3 (21%)

Bacterial infection, Grade 1-3 (65%)

Increased Creatinine, Grade 1-4 (50%)

Bilirubin increased, Grade 1-4 (42%)

Mucosal inflammation (31%)

Increased AST, Grade 1-4 (56%)

Increased ALT, Grade 1-4 (56%)

Disease relapse (21%)

Acute GVHD, Grade 2-4 (62%)

Gastrointestinal toxicity (19%)

Dysphagia (12%)

Hemorrhage (12%)

Increased Magnesium, Grade 1-4 (15%)

1-10%

Fatigue (4%)

Dyspnea (8%)

Graft failure (2%)

Fever (2%)

Black Box Warning

None

Contraindication / Caution

Contraindication/Caution:

Contraindication

omidubicel may not be appropriate for patients with a history of hypersensitivity reactions to any of its components or who cannot receive standard medical care during the transplant process. Additionally, omidubicel should not be used in patients who are not candidates for bone marrow transplantation, have active infections, or have uncontrolled medical conditions that could affect their ability to tolerate the therapy. As with any medical treatment, the decision to use omidubicel should be made on a case-by-case basis after careful consideration of the patient’s personal medical history, condition, and potential risks and benefits. It is essential to consult with a healthcare provider for more information about this therapy’s contraindications and potential risks.

Caution

Graft-versus-host disease (GVHD): omidubicel contains donor cells, which can potentially attack the recipient’s tissues and organs, leading to GVHD. Patients receiving omidubicel may require immunosuppressive therapy to prevent or manage GVHD.

Infections: Patients receiving omidubicel may be at increased risk of infections due to suppressing their immune system. Careful monitoring and management of infections are essential.

Bleeding and thrombotic events: omidubicel can affect the patient’s blood cells, potentially leading to bleeding or clotting disorders. Patients receiving omidubicel may require blood products or anticoagulation therapy to prevent or manage these complications.

Infusion-related reactions: Infusion of omidubicel can cause allergic or hypersensitivity reactions ranging from mild to severe. Patients receiving omidubicel should be closely monitored during and after the infusion for any signs of infusion-related reactions.

Secondary malignancies: Patients receiving omidubicel may be at increased risk of developing secondary malignancies, such as leukemia or lymphoma, due to the effects of the therapy on their blood cells.

Pregnancy / Lactation

Pregnancy consideration:

Pregnancy category: N/A

Lactation: N/A

Pregnancy category:

Category A: well-controlled and Satisfactory studies do not show risk to the fetus in the first/later trimester.

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology: 

omidubicel does have several critical pharmacological properties related to its ability to reconstitute a patient’s hematopoietic system. 

• Hematopoietic reconstitution: The HSCs in omidubicel can differentiate into all types of blood cells, including red blood cells, white blood cells, and platelets. When infused into a patient’s bloodstream, these HSCs migrate to the bone marrow and produce new blood cells, replacing the patient’s damaged or destroyed hematopoietic cells. 
• Immune system reconstitution: Besides producing new blood cells, the HSCs contained in omidubicel can differentiate into immune cells, including T cells, B cells, and natural killer (NK) cells. This process is critical for reconstituting a patient’s immune system following HSCT. 
• Reduced risk of GVHD: omidubicel is being studied for its potential to reduce the risk of GVHD, a complication of HSCT in which the donor cells attack the recipient’s tissues and organs. This property may be related to the ex vivo expansion process, which may lead to a more balanced composition of immune cells in the infused product. 
• Rapid engraftment: omidubicel is being studied for its potential to rapidly engraft in patients, meaning that the donor cells start producing new blood cells more quickly than traditional HSCT. This property may be related to the high number of HSCs contained in the infused product. 

Pharmacodynamics: 

Mechanism of action: The therapeutic approach works by utilizing modified allogeneic hematopoietic progenitor cells derived from cord blood, which is a source of allogeneic stem cell donors. The therapy is created using a proprietary technology that enriches HPCs using Nicotinamide. This NAM-based technology helps to prevent the activation of cellular stress, signaling pathways, accelerated proliferation, and differentiation are typically seen when HPCs are removed from their natural environment. The HPCs derived from cord blood are cultured ex-vivo in the presence of NAM to preserve their stemness and functionality. Clinical trials have demonstrated that the therapy leads to rapid neutrophil engraftment and immune system reconstitution with multiple lineages, indicating its efficacy. 

Pharmacokinetics: 

omidubicel is a cellular therapy that contains ex vivo-expanded hematopoietic stem cells (HSCs) derived from a haploidentical (half-matched) donor. As a cellular therapy, omidubicel does not undergo traditional pharmacokinetic processes, such as absorption, distribution, metabolism, and excretion. Instead, it is administered directly into the patient’s bloodstream, where the HSCs migrate to the bone marrow, producing new blood cells and immune cells. 

In general, the HSCs contained in omidubicel are believed to have a short half-life in the bloodstream and do not persist long-term in the body. Instead, they differentiate into the blood and immune cells and are eventually replaced by these newly produced cells. However, the exact kinetics of this process is not well understood. It might depend on factors such as the patient’s underlying disease, the intensity of their conditioning regimen, and the quality of the infused product. 

Regarding safety, omidubicel is being studied in clinical trials to evaluate its potential to cause adverse events, including infusion reactions, infections, and graft-versus-host disease (GVHD). These adverse events may be related to the properties of the HSCs contained in the infused product, such as their immunogenicity and differentiation potential, rather than traditional pharmacokinetic processes. 

Adminstartion

Administration: 

• Preparation: omidubicel is prepared by collecting hematopoietic stem cells (HSCs) from a healthy donor and then expanding them ex vivo (outside the body) using a proprietary process. The expanded cells are cryopreserved and then shipped to the transplant center, where they will be infused into the patient. 
• Pre-transplant conditioning: Before the infusion of omidubicel, patients typically undergo conditioning therapy to suppress their immune system and make room for new cells. This may involve chemotherapy and radiation therapy. 
• Infusion: omidubicel is infused into the patient’s bloodstream via a central venous catheter or a peripheral IV line. The infusion may take several hours, and patients are monitored closely for any signs of infusion-related reactions. 
• Recovery: After the infusion, patients are closely monitored for engraftment (the point at which the donor cells start to produce new blood cells), immune system recovery, and any potential complications, such as infections or GVHD. To manage these complications, patients may require supportive care, such as blood products or antibiotics. 

It is key to note that the administration of omidubicel can vary depending on the patient’s medical history, condition, and transplant center protocols. It is essential to consult with a healthcare provider for more information about the administration of this therapy.

Patient Information Leaflet

Patient information leaflet 

Generic Name: omidubicel 

Why do we use omidubicel? 

omidubicel is a stem cell therapy used in hematopoietic stem cell transplantation (HSCT) in patients with various hematologic malignancies and other disorders. HSCT is a procedure that involves the infusion of stem cells, typically derived from a donor, into a patient’s bloodstream to replace their damaged or destroyed hematopoietic (blood-forming) cells. omidubicel contains an ex vivo-expanded population of hematopoietic stem cells (HSCs) and is being studied as an alternative to traditional donor-derived HSCs. 

The potential uses of omidubicel include: 

• Patients who require HSCT but do not have a matched donor: Many patients who require HSCT do not have a matched donor available, which can limit their treatment options. omidubicel, derived from a haploidentical (half-matched) donor, may be an alternative option for these patients. 
• Reduced risk of graft-versus-host disease (GVHD): GVHD is a common complication of HSCT in which the donor cells attack the recipient’s tissues and organs. omidubicel is being studied for its potential to reduce the risk of GVHD, potentially improving patient outcomes and quality of life. 
• Rapid engraftment: omidubicel is being studied for its potential to rapidly engraft in patients, meaning that the donor cells start producing new blood cells more quickly than traditional HSCT. 
• Potential for outpatient treatment: Because of its reduced risk of GVHD and potential for rapid engraftment, omidubicel may be a candidate for outpatient treatment.