Omidubicel-onlv (Omisirge)

Number: 1032

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses omidubicel-onlv (Omisirge) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of omidubicel-onlv (Omisirge) is required of all Aetna participating providers and members in applicable plan designs. For precertification of omidubicel-onlv (Omisirge), contact National Medical Excellence (NME) at 877-212-8811.  

1. Criteria for Initial Approval

   Aetna considers omidubicel-onlv (Omisirge) medically necessary for the following indications: 

   1. Hematologic Malignancies

      One dose total for members 12 years of age and older with a hematologic malignancy who will receive umbilical cord blood transplantation when all of the following criteria are met: 

      1. The requested medication is being used to reduce the time to neutrophil recovery and incidence of infection; and
      2. The member will receive myeloablative conditioning therapy.
         

   2. Severe Aplastic Anemia (SAA)

      One dose total for members 6 years of age and older with severe aplastic anemia (SAA) following reduced intensity conditioning therapy.

   Aetna considers all other indications as experimental, investigational, or unproven.

2. Continuation of Therapy

   See Dosage and Administration information.

Dosage and Administration

Omidubicel-onlv is supplied as Omisirge, a cell suspension for intravenous infusion.

• For intravenous use only.
• Do not irradiate.
• Do not use a leukodepleting filter.
• Verify person's identity upon receipt, prior to thaw and prior to infusion. Do not open the metal cassettes until time of thaw.
• Thawing should only take place immediately prior to use.
• Premedicate the patient approximately 30 to 60 minutes prior to infusion.
• The recommended dose of Omisirge is a one-time infusion delivered in two separate bags.
• The CF (Cultured Fraction) bag must be administered FIRST, and infusion should not exceed 2 hours from the end of dilution. Infusion of the NF (Non-cultured) bag should not exceed 1 hour from the end of dilution.
• Administration of Omisirge should be under the supervision of a physician experienced in treatment of hematologic malignancies or severe aplastic anemia (SAA), as appropriate, in centers with expertise in hematopoietic stem cell transplants.

A single dose of Omisirge consists of:

• a Cultured Fraction (CF): a minimum of 8.0 × 10⁸ total viable cells of which a minimum of 8.7% is CD34+ cells and a minimum of 9.2 × 10⁷ CD34+ cells; and
• a Non-cultured Fraction (NF): a minimum of 4.0 × 10⁸ total viable cells with a minimum of 2.4 × 10⁷ CD3+ cells.

The CF and NF are supplied cryopreserved separately in two bags. Omisirge requires thaw and dilution with two infusion solution (IS) bags (one IS bag for the CF, and one IS bag for the NF) prior to administration. Infusion of the NF bag should begin within 1 hour after completion of the CF infusion.

Refer to full prescribing information for Omisirge for administration instructions.

Source: Gamida Cell, 2023

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
38204	Management of recipient hematopoietic progenitor cell donor search and cell acquisition
38205	Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; allogeneic
38207	Transplant preparation of hematopoietic progenitor cells; cryopreservation and storage
38208	thawing of previously frozen harvest, without washing, per donor
38240	Hematopoietic progenitor cell (HPC); allogeneic transplantation per donor
96365	Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug); initial, up to 1 hour
96366	each additional hour
HCPCS codes covered if selection criteria are met:
Omidubicel-onlv (Omisirge) –no specific code
Other HCPCS codes related to the CPB:
S2140	Cord blood harvesting for transplantation, allogeneic
S2142	Cord blood-derived stem-cell transplantation, allogeneic
ICD-10 codes covered if selection criteria are met:
C81.00 – C96.9	Malignant neoplasms of lymphoid, hematopoietic and related tissue
C96.A	Histiocytic sarcoma
C96.Z	Other specified malignant neoplasms of lymphoid, hematopoietic and related tissue
D46.0 – D46.9	Myelodysplastic syndromes
D46.A	Refractory cytopenia with multilineage dysplasia
D46.B	Refractory cytopenia with multilineage dysplasia and ring sideroblasts
D46.C	Myelodysplastic syndrome with isolated del(5q) chromosomal abnormality
D46.Z	Other myelodysplastic syndromes
D47.1	Chronic myeloproliferative disease
D61.01 - D61.3, D61.89, D61.9	Other aplastic anemias and other bone marrow failure syndromes

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Background

U.S. Food and Drug Administration (FDA)-Approved Indications 

• Omisirge is indicated for the treatment of adults and pediatric patients 12 years and older with hematologic malignancies who are planned for umbilical cord blood transplantation following myeloablative conditioning to reduce the time to neutrophil recovery and the incidence of infection.

• Omisirge is indicated for the treatment of adults and pediatric patients 6 years of age and older with severe aplastic anemia (SAA) following reduced intensity conditioning.

Omidubicel-onlv is available as Omisirge (Gamida Cell Ltd.) and is a cryopreserved nicotinamide (NAM) modified allogeneic hematopoietic progenitor cell therapy derived from cord blood consisting of 2 cell fractions; a Cultured Fraction (CF) and a Non-cultured Fraction (NF) which are both derived from the same patient-specific cord blood unit (CBU). Omisirge is manufactured by using a proprietary NAM based technology producing enriched hematopoietic progenitor cells (HPCs). As noted in clinical trials with Omisirge, ex-vivo culturing of cord blood derived HPCs with NAM present leads to preservation of their stemness, homing to the bone marrow (BM) and retained engraftment capacity as exhibited by rapid neutrophil engraftment and multi lineage immune reconstitution (Gamida Cell, 2025). 

Per the prescribing information, black box warnings for Omisirge include:

• Infusion reactions: Infusion reactions may be fatal. Monitor patients during infusion and discontinue for severe reactions. Use is contraindicated in patients with known allergy to dimethyl sulfoxide (DMSO), Dextran 40, gentamicin, human serum albumin, or bovine material
• Graft-vs-host disease (GvHD): GvHD may be fatal. Administration of immunosuppressive therapy may decrease the risk of GvHD
• Engraftment syndrome: Engraftment syndrome may be fatal. Treat engraftment syndrome promptly with corticosteroids
• Graft failure: Graft failure may be fatal. Monitor patients for laboratory evidence of hematopoietic recovery.

According to the prescribing information, Omisirge is contraindicated in individuals with a known sensitivity to dimethyl sulfoxide (DMSO), Dextran 40, gentamicin, human serine albumin or bovine material.

Per the prescribing information, Omisirge carries the following warnings and precautions:

• Malignancies of donor origin: Monitor life-long for secondary malignancies
• Transmission of serious infections: Monitor patients closely for serious infections
• Transmission of rare genetic diseases: Monitor patients for rare genetic diseases.

Per the prescribing information, adverse reactions include the following:

• Hematological malignancies: The most common adverse reactions (incidence > 20%) are infections, GvHD, and infusion and hypersensitivity reactions.
• SAA: The most common adverse reactions (incidence > 20%) are infections, hyperglycemia, skin rash, febrile neutropenia, immune thrombocytopenia, acute kidney injury, acute GvHD, hypertension, hypoxia, and infusion related reactions.

On April 17, 2023, the U.S. Food and Drug Administration (FDA) approved omidubicel-onlv (Omisirge) for use in adult and pediatric patients (12 years and older) with hematologic malignancies who are planned for umbilical cord blood transplantation following myeloablative conditioning to reduce the time to neutrophil recovery and the incidence of infection. The FDA approval was based on supporting data from Study P0501 (FDA, 2023). 

Horwitz and colleagues (2021) evaluated the safety and efficacy of Omisirge (omidubicel-onlv) in Study P0501, an open-label, multicenter, randomized, phase 3 trial of Omisirge transplantation or standard umbilical cord blood transplantation (UCBT) following myeloablative conditioning in patients with hematologic malignancies. Patients received myeloablative conditioning and prophylaxis with a calcineurin inhibitor and mycophenolate mofetil for graft-versus-host disease (GVHD). This study consisted of 125 patients, ranging in age from 13 to 65 years, who were randomized 1:1 to receive Omisirge (n=62) or standard UCB (n=63). Fifty-two patients were transplanted with Omisirge at a median CD34+ cell dose of 9.0 x 10⁶ cells/kg (range 2.1 - 47.6 x 10⁶ cells/kg). Fifty-six patients in the standard UCBT arm were transplanted with one or two cord units (66% received two cord units). The post-thaw cell dose was reported in 42 patients with the median CD34+ cell dose as 0.2 x 10⁶ cells/kg (range 0.0 - 0.8 x 10⁶ cells/kg). Multiple conditioning regimens were used, including Total Body Irradiation (TBI)-based or chemotherapy-based options. The primary efficacy outcome measures were time to neutrophil recovery following transplantation and the incidence of Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Grade 2/3 bacterial or Grade 3 fungal infections through day 100 following transplantation. Median time to neutrophil recovery was 12 days (95% confidence interval [CI], 10-14 days) for the Omisirge transplantation arm and 22 days (95% CI, 19-25 days) for the control arm (p<0.001). The cumulative incidence of neutrophil recovery was 96% for patients in the Omisirge arm and 89% for patients in the standard UCBT arm. Patients in the Omisirge transplantation arm showed a faster platelet recovery (55% vs 35% recovery by 42 days; p=0.028), and a lower incidence of first grade 2 to 3 bacterial or invasive fungal infection (37% vs 57%; p=0.027), and spent more time out of the hospital during the first 100 days after transplant (median, 61 vs 48 days; p=0.005) than in the control arm. Differences in GVHD and survival between the 2 arms were statistically insignificant. The investigators concluded that patients with Omisirge transplantation experienced faster hematopoietic recovery and a decrease in early transplant-related complications compared to standard UCBT.

On December 8, 2025, the U.S. Food and Drug Administration (FDA) granted approval to omidubicel-onlv (Omisirge) as the first  hematopoietic stem cell transplant (HSCT) therapy to treat patients with severe aplastic anemia (SAA). In addition to Omisirge being indicated for adults and pediatric patients 12 years of age and older with hematologic malignancies, its latest approval is for use in adults and pediatric patients six years of age and older with SAA following reduced intensity conditioning and for whom a compatible donor is not available. The FDA approval was based on supporting data from study 17- H-0091 (NCT 03173937)  an open-label, single center study. The study enroled patients 6 yeas of age and older 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. Of the 17 patients treated with Omisirge, 14 patients received Omisirge alone and three patients received Omisirge and haploidentical CD34+ cells. The primary efficacy outcome measure was the incidence of early and sustained neutrophil recovery, defined as ANC ≥500 cels/µl for 3 consecutive measurements on different days by Day 26, maintained at Days 42 and 100 posttransplant. Secondary outcome measures included neutrophil recovery (days to first of three consecutive ANC≥500 cels/µL), red blood cel (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). Omisirge demonstrated early and sustained engraftment in 12 of 14 patients in the efficacy population with a median time to neutrophil recovery of 11 days (range seven to 20 days) (FDA, 2025; Gamida Cell, 2025).

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References