Omidubicel-onlv (Omisirge)

Number: 1032

Table Of Contents

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

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

    Umbilical Cord Blood Transplantation

    Aetna considers omidubicel-onlv (Omisirge) (one dose total) medically necessary for members 12 years of age and older who will receive umbilical cord blood transplantation when all of the following criteria are met:

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

    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. 

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

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:
S2142 Cord blood-derived stem-cell transplantation, allogeneic

ICD-10 codes covered if selection criteria are met:
C81.0 – 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

Background

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

  • Omisirge is a nicotinamide modified allogeneic hematopoietic progenitor cell therapy derived from cord blood indicated for use in 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.

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, 2023). 

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, the most common adverse reactions (incidence > 20%) are infections, GvHD, and infusion reaction. 

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. 

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.

References

The above policy is based on the following references:

  1. Gamida Cell Ltd. OMISIRGE® (omidubicel-onlv) suspension for infusion, for intravenous use. Prescribing Information. Jerusalem, Israel: Gamida Cell: revised February 202a4.
  2. Horwitz ME, Stiff PJ, Cutler C, et al. Omidubicel vs standard myeloablative umbilical cord blood transplantation: results of a phase 3 randomized study. Blood. 2021;138(16):1429-1440. 
  3. U.S. Food and Drug Administration (FDA). FDA approves omidubicel to reduce time to neutrophil recovery and infection in patients with hematologic malignancies. Drugs. Silver Spring, MD: FDA; April 17, 2023.