PPA News

Posted by: Gilbert Burckart on Dec 8, 2020

On November 25, 2020, the U.S. Food and Drug Administration (FDA) approved DANYELZA (naxitamab-gqgk) for use in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) 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).

The approved recommended dosage of DANYELZA is 3 mg/kg/day (up to 150 mg/day), administered as an intravenous infusion after dilution on Days 1, 3, and 5 of each treatment cycle (first infusion over 60 minutes and subsequent infusions over 30-60 minutes as tolerated). Treatment cycles are repeated every 4 weeks until complete response or partial response, followed by 5 additional cycles every 4 weeks. Subsequent cycles may be repeated every 8 weeks. Discontinue DANYELZA and GM-CSF for disease progression or unacceptable toxicity. Administer GM-CSF subcutaneously prior to and during each treatment cycle as recommended.


  • Serious Infusion-Related Reactions: DANYELZA can cause serious infusion reactions, including cardiac arrest, anaphylaxis, hypotension, bronchospasm, and stridor. Premedicate prior to each DANYELZA infusion as recommended. Reduce the rate, interrupt infusion, or permanently discontinue DANYELZA based on severity.
  • Neurotoxicity: DANYELZA can cause severe neurotoxicity, including severe neuropathic pain, transverse myelitis, and reversible posterior leukoencephalopathy syndrome (RPLS). Premedicate to treat neuropathic pain as recommended. Permanently discontinue DANYELZA based on the adverse reaction and severity.

DANYELZA is contraindicated in patients with a history of severe hypersensitivity reaction to naxitamab-gqgk. Reactions have included anaphylaxis. Additional information regarding dosage and administration as well as warnings and precautions about serious infusion-related reactions, neurotoxicity, hypertension, and embryo-fetal toxicity can be found in the full prescribing information linked below.

Mechanism of Action (MOA) and Pharmacokinetics (PK)

MOA: Naxitamab-gqgk is a GD2-binding monoclonal antibody.

General PK: The geometric mean (CV%) maximum plasma concentration (Cmax) of naxitamab-gqgk was 57.4 μg/mL (49%) following DANYELZA 3 mg/kg intravenous infusion over 30 minutes.

Elimination: The mean terminal half-life of naxitamab-gqgk was 8.2 days.

Metabolism: Naxitamab-gqgk is expected to be metabolized into small peptides by catabolic pathways.

Immunogenicity: In a clinical trial, 2 of 24 (8%) patients tested positive for anti-drug antibodies (ADA) after treatment with DANYELZA. In another clinical trial, 27 of 117 patients (23%) tested positive for ADA after treatment with DANYELZA by an assay that was not fully validated; therefore, the incidence of ADA may not be reliable.

Use in Specific Populations

Population pharmacokinetic analyses suggest that age (range: 1 to 34 years), sex, and race have no clinically important effect on the clearance of naxitamab-gqgk. The naxitamab-gqgk systemic exposure (AUC) at 150 mg/day (450 mg per cycle) for patients with body weight over 50 kg is not expected to differ clinically from that of the naxitamab-gqgk exposures at 3 mg/kg/day (9 mg/kg per cycle) for patients with body weight of 30 to 50 kg.

Efficacy and Safety

The efficacy of DANYELZA in combination with GM-CSF was evaluated in two open-label, single arm trials in patients with high-risk neuroblastoma with refractory or relapsed disease in the bone or bone marrow. Additional information regarding the efficacy trials can be found in the full prescribing information linked below.

The most common adverse reactions (≥25%) are infusion-related reaction, pain, tachycardia, vomiting, cough, nausea, diarrhea, decreased appetite, hypertension, fatigue, erythema multiforme, peripheral neuropathy, urticaria, pyrexia, headache, injection site reaction, edema, anxiety, localized edema, and irritability. The most common Grade 3 or 4 laboratory abnormalities (≥5%) are decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased platelet count, decreased potassium, increased alanine aminotransferase, decreased glucose, decreased calcium, decreased albumin, decreased sodium, and decreased phosphate.

Full prescribing information is available at https://go.usa.gov/x76wd.

Visit Drugs@FDA at http://go.usa.gov/cMsjT for prescribing and patient information, approval letters, reviews and other information for FDA-approved drug products, which are often available shortly following approval.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at https://www.fda.gov/safety/medwatch/default.htm, by faxing (1-800-FDA-0178), or by mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).

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This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA (and sent to PPA members by the Pediatric Pharmacy Association).