General Information

Danyelza (naxitamab-gqgk) is a humanized, monoclonal antibody that targets the ganglioside GD2, which is highly expressed in various neuroectoderm-derived tumors and sarcomas.

Danyelza is specifically indicated, 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.

Danyelza is supplied as an injection for intravenous administration. The 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. 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.

Mechanism of Action

Danyelza (naxitamab-gqgk) binds to the glycolipid GD2. GD2 is a disialoganglioside that is overexpressed on neuroblastoma cells and other cells of neuroectodermal origin, including the central nervous system and peripheral nerves. In vitro, naxitamab-gqgk was able to bind to cell surface GD2 and induce complement dependent cytotoxicity (CDC) and antibody dependent cell-mediated cytotoxicity (ADCC).

Side Effects

Adverse effects associated with the use of Danyelza may include, but are not limited to, the following:

• 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
• irritability
• Grade 3 or 4 laboratory abnormalities

The Danyelza drug label comes with the following Black Box Warning: Serious Infusion-Related Reactions: Danyelza can cause serious infusion reactions, including cardiac arrest, anaphylaxis, hypotension, bronchospasm, and stridor. Pre-medicate 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). Pre-medicate to treat neuropathic pain as recommended. Permanently discontinue Danyelza based on the adverse reaction and severity.

Clinical Trial Results

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

The FDA approval of Danyelza was based on two open-label, single arm trials in patients with high-risk neuroblastoma with refractory or relapsed disease in the bone or bone marrow, Study 201 and Study 12-230.

Study 201: The efficacy of Danyelza in combination with GM-CSF was evaluated in Study 201, a multicenter open-label, single arm trial, in a subpopulation of patients who had refractory or relapsed high-risk neuroblastoma in the bone or bone marrow and demonstrated a partial response, minor response, or stable disease to prior therapy. Patients with progressive disease were excluded. All patients received at least one systemic therapy to treat disease outside of the bone or bone marrow prior to enrollment. Patients received Danyelza 9 mg/kg/cycle administered as three separate intravenous infusions of 3 mg/kg on Days 1, 3 and 5 of each cycle. Patients received GM-CSF subcutaneously at 250 µg/m2 /day on Days -4 to 0 and at 500 µg/m2 /day on Days 1 to 5. Preplanned radiation to the primary site was allowed. The major efficacy outcome measure was overall response rate (ORR) according to the revised International Neuroblastoma Response Criteria (INRC), as determined by independent pathology and imaging review and confirmed by at least one subsequent assessment. An additional efficacy outcome measure was duration of response (DOR). Twenty-two patients were included in the efficacy analysis. The overall response rate was 45%, with a complete response rate  of 36% and a partial response rate of 9%. The median duration of response was 6.2 months; the percentage of responders with a DOR ≥ 6 months was 30%. 

Study 12-230: The efficacy of Danyelza in combination with GM-CSF was evaluated in a single center, open-label, single arm trial, in a subpopulation of patients who had relapsed or refractory high-risk neuroblastoma in bone or bone marrow and demonstrated a partial response, minor response, or stable disease to prior therapy. Patients with progressive disease were excluded. All patients received at least one systemic therapy to treat disease outside of the bone or bone marrow prior to enrollment. Patients were required to have received at least one dose of Danyelza at a dose of 3 mg/kg or greater per infusion and have evaluable disease at baseline according to independent review per the revised INRC. Patients received Danyelza 9 mg/kg/cycle administered as three separate intravenous infusions of 3 mg/kg (on Days 1, 3 and 5) in the first week of each cycle. Patients received GM-CSF subcutaneously at 250 µg/m2 /day on Days -4 to 0 and at 500 µg/m2 /day on Days 1 to 5. Radiation to non-target bony lesions and soft tissue lesions was permitted at the investigator’s discretion; assessment of response excluded sites that received radiation. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR), as determined by independent pathology and imaging review according to the revised INRC and confirmed by at least one subsequent assessment. 38 patients were included in the efficacy analysis. The overall response rate was 34%, with a complete response rate of 26% and a partial response rate of 8%. Duration of Response Responders with DOR ≥ 6 months was 23%.