Omidubicel-Onlv - Mechanism of Action, Indications, Dosage, Precautions, and Adverse Drug Reactions

Overview:

Omidubicel is a cord blood-derived nicotinamide-modified hematopoietic progenitor cell treatment used as an allogeneic stem cell donor. It prevents hematopoietic stem and progenitor cell differentiation and increases the functionality. This therapy is useful for patients who require stem cell transplantation for blood malignancies but cannot find a related or unrelated donor due to high-grade human leukocyte antigen (HLA)-matching. Umbilical cord blood can be used as an alternative cell source, reducing the risk of graft failure or graft-versus-host disease. On April 17, 2023, the Food and Drug Administration (FDA) authorized the use of Omidubicel-only in patients 12 years of age and older with hematologic malignancies who are scheduled to receive cord blood transplantation after myeloablative conditioning to reduce the neutrophil recovery time and the infection risk.

Dosage Forms and Strengths:

Omidubicel is a cell suspension intended for intravenous administration.

A single dose of Omidubicel contains the following components:

• A cultured fraction (CF) containing a minimum of 8.0 × 108 total viable cells. This includes at least 8.7 percent of CD34+ cells and 9.2 × 107 CD34+ cells.

• A non-cultured fraction (NF) containing at least 4.0 × 108 total viable cells and at least 2.4 × 107 CD3+ cells.

For Patients

What Are Hematologic Malignancies?

Hematologic malignancies are cancers that arise in blood-forming tissue or immune system cells. Hematologic cancers are classified into three types: leukemia (blood malignancies typically originate in the bone marrow and result in abnormal blood cells, known as blasts or leukemia cells), lymphoma (a malignancy that affects the lymphatic system, which is a critical component of the body's immune system), and multiple myeloma (a malignancy of plasma cell, a type of white blood cells). These tumors form when the excessive proliferation of abnormal cells exceeds the development of normal blood cells, interfering with normal functioning. Fatigue, weight loss, night sweats, and lymph node swelling are some symptoms.

How Does the Drug Work?

Omidubicel is a freeze-dried cord blood-derived nicotinamide-modified allogeneic hematopoietic progenitor cell therapy that improves the functionality of patient-specific umbilical cord blood (UCB) hematopoietic progenitor cells (HPCs). The treatment is separated into two cell fractions: CD133+ (cultured fraction) and CD133 (non-cultured fraction). Nicotinamide is used for expanding CD133+ or CF cells, which inhibit differentiation, increase the frequency of CD34+ hematopoietic progenitor cells (HPCs), and decrease lineage-committed progenitor cells. This avoids the rapid proliferation, differentiation, cellular stress, and signaling cascades when HPCs are removed from the usual setting. Omidubicel improves the ability of patients with hematologic malignancies who do not have human leucocyte antigen (HLA)-matched related donors to make blood and immune cells.

Why Is Omidubicel-Only Prescribed?

Omidubicel is approved for use in people aged twelve and over with blood cancers (hematologic malignancies) undergoing umbilical cord blood transplantation after myeloablative conditioning to shorten the neutrophil recovery period and decrease the risk of infection.

How Should Omidubicel-Only Be Used?

• Omidubicel-only is a cell therapy that is used to treat individuals with blood malignancies who require a stem cell transplant. It is given as a single intravenous infusion.

• Each patient-specific dose comprises a cultured fraction (CF) and a non-cultured fraction (NF). Within one hour of completing the CF infusion, the CF bag is administered first, followed by the NF bag.

• Patients are given an antihistamine, Hydrocortisone, and Acetaminophen premedication 30 to 60 minutes before taking Omidubicel.

• Each Omidubicel unit is customized for the patient.

• The probability of a manufacturing failure is eight percent. A second manufacturing attempt may be considered if this occurs. During the preinfusion period, additional chemotherapy may be required to compensate for the delay in developing a new medication, thus increasing the chances of side effects.

What Special Precautions Should Be Taken?

• Hypersensitivity Reaction: Patients who experience any signs and symptoms of hypersensitivity reactions, such as wheezing (breathing with a loud whistling sound), swelling, itching, or hives, should notify the doctor.

• Infusion Reactions: Any signs or symptoms of infusion reactions, such as fever, chills, exhaustion, tachycardia (increased heart rate), hypoxia (inadequate quantities of oxygen in the biological tissues), severe nausea, severe vomiting, diarrhea, muscle pain, joint pain, low blood pressure, high blood pressure, or dizziness or lightheadedness, should be reported immediately.

• Graft-Versus-Host-Disease: Any signs and symptoms of graft versus host disease, such as rash, diarrhea, or eye yellowing, should be reported immediately.

• Engraftment Syndrome: Any signs and symptoms of engraftment syndrome, such as fever, rash, or an unexpected increase in body weight, should be reported immediately to the doctors.

• Graft Failure: Primary graft failure, a potentially fatal condition, can occur.

How Is Omidubicel Administered?

• Omidubicel is only for intravenous use and does not irradiate.

• Prevent the usage of a leukocyte-depleting filter.

• Wait to open the metal cassettes until the weather has thawed.

• The patient's identity must be confirmed before thawing and infusion.

• Thawing should occur immediately before usage.

• Omidubicel should be administered under a clinician with experience treating hematologic malignancies in centers with expertise in hematopoietic stem cell transplants.

• The patient should receive premedication 30 to 60 minutes before the infusion.

• Before administration, Omidubicel must be thawed and diluted with two infusion solution (IS) bags (one IS bag for the CF (cultured fraction) and one for the NF (non-cultured fraction) ).

• The CF and NF are cryopreserved in separate bags. The CF bag must be given first, and the infusion should last up to two hours after dilution. The NF bag should be infused within one hour of the completion of dilution.

What Are the Side Effects of Omidubicel-Only?

The most common side effects are infections, graft versus host disease, and infusion reactions (incidence over 20 percent). Unwanted side effects of Omidubicel-only might require medical treatment. The most common side effects are

• Agitation.

• Black stools.

• Bloody nose.

• Bloody urine.

• Blue lips, fingernails, and skin.

• Blurred vision.

• Cold flu-like symptoms.

• Coughing.

• Constipation.

• Decreased urine output.

• Depression.

• Diarrhea.

• Difficulty swallowing.

• Dizziness.

• Fever, chills, and headache.

• Hostility (the unjustified expression of anger, hatred, or antagonism, frequently directed at people or inanimate objects).

• Increased blood pressure.

• Increased thirst.

• Irritability.

• Lethargy.

• Loss of appetite.

• Lower back or side pain.

• Muscle twitching.

• Nausea or vomiting.

• Discomfort in the throat or chest while swallowing.

• Painful or difficult urination.

• Pounding in the ears.

• Seizures (An abrupt and uncontrollable increase in brain electrical activity can cause changes in behavior, movements, feelings, and consciousness levels).

• Skin rash.

• Slow or fast heartbeat.

• Sores, ulcers, white spots on the lips, tongue, or inside the mouth.

• Stupor (a condition in which a person is practically unconscious and their ideas are unclear).

• Swelling of the face, fingers, or lower legs.

• Swollen glands.

• Difficulty breathing.

• Unusual weakness.

• Vomiting blood or material like coffee grounds.

• Weight gain or loss.

• Yellow skin and eyes.

Some side effects may occur that might not demand medical attention. These side effects may fade as the body adjusts to the medicine. The doctor might direct to avoid or lessen some of these side effects. Consult the doctor if any of the following side effects continue or become difficult to manage.

The more frequent ones are

• Pain.

• Difficulty swallowing.

Other adverse effects that have not been listed may occur in some patients. Check with the doctor if patients observe any other side effects.

Storage:

Omidubicel comes in two containers: a liquid nitrogen dry vapor shipper at -150°C that contains the two cryopreserved cell fractions and a chimerism testing sample(s), and a chilled shipping container at two to eight degrees Celsius that contains two Infusion Solutions. It is delivered to a transplant facility for a specific patient. The IS bags are refrigerated in two to eight degrees Celsius storage until the CF and NF thaw.

What Can Be Done in the Event of an Overdose?

Overdosed patients are more likely to experience serious side effects such as severe infusion reactions and Graft-Versus-Host Disease (GVHD). Symptomatic and supportive care are advised in the case of an overdose.

For Doctors:

Indications:

Omidubicel is authorized for use in adults and children 12 years and older with hematologic malignancies awaiting cord blood transplantation after myeloablative conditioning to reduce the neutrophil recovery period and the risk of infection.

What Are the Pharmacological Aspects of Omidubicel-Onlv?

Pharmacodynamics:

Omidubicel is a cord blood-derived nicotinamide-modified allogeneic hematopoietic progenitor cell treatment. Using Omidubicel results in rapid and extensive immunological reconstitution of dendritic cells, monocytes, natural killer (NK) cells, CD4+ T cells, and CD8+ T cells as early as one week post-transplantation. There is a significant linear connection between the CD34+ cell concentration and the reconstitution of NK and T-cells in the Cultured Fraction (CF) of Omidubicel. The rates of neutrophil recovery are also substantially correlated with overall CD34+ cell counts and Omidubicel dosage. Higher CD34+ cell dosages result in shorter days of neutrophil recovery. Using Omidubicel can result in serious side effects, including graft versus host disease, engraftment syndrome, and graft failure, and is linked to an increased risk of infections and infusion reactions.

Mechanism of Action:

Omidubicel is a nicotinamide (NAM) modified allogeneic hematopoietic progenitor cell treatment produced from cord blood, which is used as a source of allogeneic stem cells. It is created using a proprietary NAM-based method that produces enriched HPCs. NAM technology prevents the generation of rapid proliferation, differentiation, cellular stress, and signaling pathways that occur when HPCs are isolated from the native setting. Ex-vivo culture of cord blood-derived HPCs in the presence of NAM results in retaining the stemness, homing to the bone marrow (BM), and engraftment potential, as evidenced by fast neutrophil engraftment and multi-lineage immune reconstitution in Omidubicel clinical trials.

Half-Life in Adults: Omidubicel has little pharmacokinetic data.

Pharmacokinetics: Omidubicel has little pharmacokinetic data.

Clinical Trials

An open-label, multicenter, randomized trial comparing Omidubicel-only transplantation to unmanipulated Umbilical Cord Blood (UCB) transplantation in patients with hematologic malignancies. The trial included 125 patients, 62 of whom received Omidubicel-only and 63 of whom received UCB.The primary effectiveness results were the time to neutrophil recovery after transplantation and the incidence of grade 2 or 3 bacterial infections or grade 3 fungus infections at day 100 after transplantation. The median time required for neutrophil recovery was 12 days for the Omidubicel-only group and 22 days for the UCB group. Neutrophil recovery occurred in eighty-seven percent of patients in the Omidubicel-only group and eighty-three percent in the UCB group. Through Day 100 post-transplantation, the incidence of Grade 2 or 3 bacterial or Grade 3 fungal infections in the two groups was 39 percent and 60 percent, respectively. Prescribing materials for Omidubicel-only include a warning regarding fatal or life-threatening infusion reactions, Graft versus Host Disease (GvHD), engraftment syndrome, and graft failure. Acute GvHD occurred in 58 percent of patients, chronic GvHD in 35 percent, and graft failure in three percent. Pain (33 percent), mucositis (31 percent), hypertension (25 percent), and gastrointestinal toxicity (19 percent) were the main grade 3 to 5 adverse events in subjects with hematologic malignancies in this trial.

What Are the Contraindications of Omidubicel-Onlv?

Reactivity with Dimethyl Sulfoxide (DMSO), Dextran 40, Gentamicin, human serum albumin, or bovine compound is known.

Warnings and Precautions:

The warnings and precautions associated are as follows:

• Infusion Reactions: Infusion reactions are potentially lethal. Observe patients during infusion and stop if serious reactions occur.

• Graft-Vs-Host Disease (GvHD): GvHD is potentially lethal. Immunosuppressive medication could minimize the risk of GvHD.

• Engraftment Syndrome: Engraftment syndrome is a serious condition. Corticosteroids should be used promptly to treat engraftment syndrome.

• Graft Failure: Graft failure is fatal. Patients should be monitored for laboratory signs of hematopoietic recovery.

• Secondary Malignancies of Donor Origin: Patients should be monitored for secondary malignancies for the rest of their lives. If a secondary tumor develops following therapy with Omidubicel, contact Gamida Cell.

• Transmission of Serious Illnesses: Monitor patients for signs of serious infections.

• Rare Genetic Disease Transmission: Keep track of people who have rare genetic disorders.

What Are the Drug Interactions of Omidubicel-Onlv?

There have been no drug interaction investigations with Omidubicel.

Specific Populations:

• Pregnancy: There is no accessible data on Omidubicel's use in pregnant women or its potential fetal damage. Omidubicel should only be used during pregnancy if the potential benefits outweigh the risks to the fetus. For clinically recognized pregnancies in the United States, the risks of serious birth abnormalities and miscarriage are estimated to be two to four percent and 15 to 20 percent, respectively.

• Lactation: There is no information on Omidubicel's presence in human milk, its effect on breastfed infants, and milk production.

• Female and Male Reproductive Potential: Before beginning the conditioning plan for Omidubicel, females with reproductive potential should be tested for pregnancy. Patients on a conditioning regimen must use effective contraception. However, there is inadequate exposure data to prescribe contraceptive duration. There is no data on the effect of Omidubicel on fertility.

• Pediatric Use: Omidubicel's safety and efficacy have been established in teenagers but not in pediatric patients under 12.

• Geriatric Use: Elderly use cannot be determined as clinical studies did not involve patients aged 65 and above.