Medical Drug Criteria (MDC)

Policy Num:       P1.001.004
Policy Name:     DANYELZA® (naxitamab-gqgk)
Policy ID:          [P1.001.004]  [Ac / B / M+ / P+]  [0.00.00]

Last Review:       September 22, 2025
Next Review:      September 20, 2026
 

Related MDC:None

DANYELZA^®
 (naxitamab-gqgk)

Summary

Danyelza (naxitamab-gqgk) is a GD2-binding monoclonal antibody indicated, in combination with granulocyte-macrophage colony-stimulating factor (GMCSF), for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

OBJECTIVE

To provide evidence-based, safe, and clinically appropriate use of Danyelza® in pediatric patients with relapsed or refractory high-risk neuroblastoma.

Policy Statements

Initial Coverage (6 months)
 
All of the following must be met:
 
1. Diagnosis: Relapsed/refractory high-risk neuroblastoma with disease in bone or bone marrow.
 
 2. Age: ≥1 year.
  
3. Response: Documented ≥partial response to prior therapy.
  
4. Concomitant therapy: Will be given with GM-CSF.
  
5. Prescriber: Pediatric oncologist.
  
6. Administration: In setting equipped for management of severe infusion reactions.
 
  
Reauthorization (6–12 months)
 
Evidence of benefit (ongoing response or disease stability).
 
Tolerability without grade ≥3 unresolved toxicity.
 
 
Non-Coverage
 
Patients <1 year.
 
Use outside FDA-approved indication or without compendia support.
 
Monotherapy use without GM-CSF.
 
Disease not involving bone/bone marrow.

Policy Guidelines

Required Medical Documentation
 
Pathology or histology confirming neuroblastoma, with INRG risk classification.
 
Imaging/biopsy showing bone/bone marrow involvement.
 
Treatment history with evidence of ≥partial response to prior therapy.
 
Performance status (Lansky ≥50 or ECOG 0–2).
 
Concomitant GM-CSF treatment plan.
 
Prescriber statement from pediatric oncology specialist.
 
Monitoring and management plan for infusion-related reactions and neurologic adverse events.

DOSAGE/ADMINISTRATION

Dose: 3 mg/kg/day (max 150 mg/day) on Days 1, 3, 5 of each 28-day cycle.
 
Concomitant GM-CSF: 250 µg/m²/day SC Days –4 to 0, then 500 µg/m²/day Days 1–5 & 8–12 of each cycle.
 
Premedication: Analgesics (morphine/hydromorphone), antihistamines, acetaminophen, corticosteroids.
 
Duration: Continue until progression or unacceptable toxicity.

REQUIRED MEDICAL INFORMATION

Initiation of naxitamab-gqgk (Danyelza) injection meets the definition of medical necessity with ANY of the following conditions when ALL associated criteria are met:

1. Relapsed or refractory high-risk neuroblastoma in the bone or bone marrow

      a. Member is diagnosed with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow

      b. Member demonstrated a partial response, minor response, or stable disease to one prior systemic therapy

      c. Naxitamab-gqgk is use is in combination with a granulocyte-macrophage colonystimulating factor (i.e., sargramostim)

      d. Naxitamab-gqgk is used in combination with premedications to mitigate the risk of infusion reactions (e.g., corticosteroids) and neurotoxicity (e.g., gabapentin)

      e. Naxitamab-gqgk is not used in combination with dinutuximab (Unituxin)

      f. The dose does not exceed 3 mg/kg/day on Day 1, 3, and 5 every 4 weeks of each treatment cycle until complete or partial response. Five additional treatment cycles are given every 4 weeks following a complete or partial response and then subsequent cycles every 8 weeks

2. Other FDA-approved or NCCN supported diagnosis (not previously listed above)

    a. Member meets one of the following:

         i. Member is diagnosed with a condition that is consistent with an indication listed in the product’s FDA-approved prescribing information (or package insert) AND member meets any additional requirements  listed in the “Indications and Usage” section of the FDA-approved prescribing information (or package insert)

          ii. Indication AND usage is recognized in NCCN Drugs and Biologics Compendium as a Category 1 or 2A recommendation

   b. The dose does not exceed 3 mg/kg/day on Day 1, 3, and 5 every 4 weeks of each treatment cycle until complete or partial response. Five additional treatment cycles are given every 4 weeks following a complete or partial response and then subsequent cycles every 8 weeks

Continuation of naxitamab-gqgk (Danyelza) injection meets the definition of medical necessity when ALL of the following criteria are met:

1. An authorization or reauthorization for naxitamab-gqgk (Danyelza) injection has been previously approved by Triple-S or another health plan in the past 2 years for the treatment of relapsed or refractory high-risk neuroblastoma in the bone or bone marrow or other FDA-approved or NCCN supported diagnosis; OR the member has previously met ALL indication-specific criteria.

2. The member has a beneficial response to treatment (i.e., no disease progression or toxicity)

3. Naxitamab-gqgk is not used in combination with dinutuximab (Unituxin) 4. The dose does not exceed 3 mg/kg/day on Day 1, 3, and 5 every 4 weeks of each treatment cycle until complete or partial response. Five additional treatment cycles are given every 4 weeks following a complete or partial response and then subsequent cycles every 8 weeks

EXCLUSION CRITERIA

Age <1 year.
 
Use without GM-CSF.
 
Absence of bone/bone marrow disease.
 
Inadequate hepatic, renal, or cardiac function outside PI thresholds.
 
Active uncontrolled infection or uncontrolled pain.
 
Unresolved ≥Grade 3 toxicity from prior naxitamab.
 
Pregnancy or breastfeeding.

Background / Regulatory Status

FDA accelerated approval Nov 2020; PI updated Dec 2023.
 
EMA conditional approval (2021).
 
NCCN 2025 Pediatric Oncology lists Danyelza® as a Category 2A recommendation.

BENEFIT APPLICATION

BlueCard/National Account Issues:  Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered. Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.

OTHER CRITERIA

Must be prescribed by a board-certified pediatric oncologist/hematologist.
 
Infusion must occur in a tertiary pediatric oncology center with intensive care support.
 
Documented use of standardized premedication (opioids, antihistamines, acetaminophen, corticosteroids).
 
Response assessment by MIBG, CT/MRI, or bone marrow biopsy at baseline and follow-up.
 
Discontinue if:
 
Progressive disease despite therapy,
 
Life-threatening/unmanageable toxicity,
 
No clinical benefit after 2–3 cycles.
 
 
Concurrent investigational therapies discouraged unless part of a clinical trial.

Validate that the treatment regimen is following the most up to date NCCN guidelines recommendations.

RATIONAL

Provides treatment in a pediatric population with limited salvage options.
 
Clinical trials demonstrated meaningful response rates with manageable toxicity under specialized care.
 
Aligns with NCCN and PI guidance.

PRACTICE GUIDELINES

NCCN Pediatric Neuroblastoma (2025): Danyelza® + GM-CSF is a salvage option in relapsed/refractory disease with bone/bone marrow involvement.
 
Must be administered in specialized centers with expertise in GD2-directed therapy.

References

1. Danyelza (naxitamab) [prescribing information]. New York, NY: Y-mAbs Therapeutics Inc;  03/2024

2. Florida Blue Medical Coverage Guidelines. http://mcgs.bcbsfl.com/MCG

3. https://danyelzahcp.com/wp-content/themes/DANYELZA_HCP_120/download-pdf/DANYELZA-billing-and-coding-guide.pdf

4. FDA Prescribing Information, Danyelza® (naxitamab-gqgk). December 2023.
  
5. NCCN Clinical Practice Guidelines in Oncology: Pediatric Neuroblastoma, 2025.

Codes

Applicable Modifiers

As per correct coding guidelines

Policy History