Naxitamab

FDA Drug Information • Also known as: Danyelza

Brand Names: Danyelza
Dosage Form: SOLUTION, CONCENTRATE
Product Type: DRUG FOR FURTHER PROCESSING

⚠ Boxed Warning (Black Box)

WARNING: SERIOUS INFUSION-RELATED REACTIONS and NEUROTOXICITY WARNING: SERIOUS INFUSION-RELATED REACTIONS and NEUROTOXICITY See full prescribing information for complete boxed warning 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 ( 2.2 , 2.3 , 4 , 5.1 ). 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 ( 2.2 , 2.3 , 5.2 ). Serious Infusion-Related Reactions DANYELZA can cause serious infusion reactions, including cardiac arrest, anaphylaxis, hypotension, bronchospasm, and stridor. Infusion reactions of any Grade occurred in 94-100% of patients. Severe infusion reactions occurred in 32-68% and serious infusion reactions occurred in 4 - 18% of patients in DANYELZA clinical studies [see Warnings and Precautions (5.1) ]. Premedicate prior to each DANYELZA infusion as recommended and monitor patients for at least 2 hours following completion of each infusion. Reduce the rate, interrupt infusion, or permanently discontinue DANYELZA based on severity [see Dosage and Administration (2.2 , 2.3) , Contraindications (4) , and Warnings and Precautions (5.1) ]. Neurotoxicity DANYELZA can cause severe neurotoxicity, including severe neuropathic pain, transverse myelitis and reversible posterior leukoencephalopathy syndrome (RPLS). Pain of any Grade occurred in 94-100% of patients in DANYELZA clinical studies [see Warnings and Precautions (5.2) ]. Premedicate to treat neuropathic pain as recommended. Permanently discontinue DANYELZA based on the adverse reaction and severity [see Dosage and Administration (2.2 , 2.3) and Warnings and Precautions (5.2) ].

Description

11 DESCRIPTION Naxitamab-gqgk is a glycolipid disialoganglioside (GD2)-binding recombinant humanized monoclonal IgG1 antibody, that contains human framework regions and murine complementarity-determining regions. Naxitamab-gqgk is produced in a Chinese hamster ovary cell line and has an approximate molecular weight of 144 kDa without glycosylation. DANYELZA (naxitamab-gqgk) injection is a sterile, preservative-free, clear to slightly opalescent and colorless to slightly yellow solution for intravenous infusion. Each single-dose vial contains 40 mg of naxitamab-gqgk in 10 mL of solution. Each mL of solution contains 4 mg of naxitamab-gqgk, and citric acid anhydrous (0.71 mg), poloxamer 188 (1.5 mg), sodium chloride (7.01 mg), sodium citrate (6.3 mg), and Water for Injection, USP. The pH is approximately 5.7.

What Is Naxitamab Used For?

1 INDICATIONS AND USAGE DANYELZA is 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. This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies (14) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). DANYELZA is a GD2-binding monoclonal antibody 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. 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). ( 1 )

Dosage and Administration

2 DOSAGE AND 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. ( 2.1 ) 2.1 Recommended Dosage The recommended dosage of DANYELZA is 3 mg/kg/day (up to 150 mg/day) on Days 1, 3, and 5 of each treatment cycle, administered as an intravenous infusion after dilution [see Dosage and Administration (2.4 and 2.5) ] in combination with GM-CSF subcutaneously as shown in Table 1. Refer to the GM-CSF Prescribing Information for recommended dosing information. 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 pre-infusion medications and supportive treatment, as appropriate, during infusion. [see Dosage and Administration (2.2) ] The recommended dosage regimen for each treatment cycle is described below and in Table 1: Days -4 to 0: administer GM-CSF 250 µg/m 2 /day by subcutaneous injection, beginning 5 days prior to DANYELZA infusion. Days 1 to 5: administer GM-CSF 500 µg/m 2 /day by subcutaneous injection. Administer at least 1 hour prior to DANYELZA administration on Days 1, 3, and 5. Days, 1, 3, and 5: administer DANYELZA 3 mg/kg/day (up to 150 mg/day) by intravenous infusion. Table 1 Dose and Schedule of GM-CSF and DANYELZA Within One Treatment Cycle Day -4 -3 -2 -1 0 1 2 3 4 5 Subcutaneous GM-CSF 250 µg/m 2 /day 500 µg/m 2 /day Intravenous DANYELZA 3 mg/kg/day 3 mg/kg/day 3 mg/kg/day Missed Dose If a DANYELZA dose is missed, administer the missed dose the following week by Day 10. Administer GM-CSF 500 µg /m 2 /day on the first day of the DANYELZA infusion, and on the day before and on the day of the second and third infusion, respectively (i.e. a total of 5 days with 500 µg /m 2 /day). 2.2 Premedications and Supportive Medications Pain Management Prior to and During Infusion [see Warnings and Precautions (5.2) ]: Five days prior to the first infusion of DANYELZA in each cycle, initiate a 12-day course (Day -4 through Day 7) of prophylactic medication for neuropathic pain, such as gabapentin. Administer oral opioids 45-60 minutes prior to initiation of each DANYELZA infusion and additional intravenous opioids as needed for breakthrough pain during the infusion. Consider use of ketamine for pain that is not adequately controlled by opioids. Premedication: Reduce Risk of Infusion-Related Reactions and Nausea/Vomiting [see Warnings and Precautions...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are also described elsewhere in the labeling: Serious Infusion-Related Reactions [see Warnings and Precautions (5.1) ] Neurotoxicity [see Warnings and Precautions (5.2) ] Myocarditis [see Warnings and Precautions (5.3) ] Hypertension [see Warnings and Precautions (5.4) ] Orthostatic Hypotension [see Warnings and Precautions (5.5) ] 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 ( 6.1 ). 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 ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Y-mAbs Therapeutics, Inc, at 1-833-339-6227 (1-833-33YMABS), or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of DANYELZA in combination with GM-CSF was evaluated in patients with refractory or relapsed high-risk neuroblastoma in bone or bone marrow who had demonstrated a partial response, minor response, or stable disease following initial or subsequent therapy, and in patients who were in second complete remission, from two open-label, single arm studies, Study 201 (n=25) and Study 12-230 (n=72). Patients received DANYELZA 9 mg/kg/cycle administered as three separate intravenous infusions of 3 mg/kg (Day 1, 3 and 5) in the first week of each cycle. Patients also received GM-CSF 250 µg/m 2 /day subcutaneously on Days -4 to 0 and GM-CSF 500 µg/m 2 /day subcutaneously on Days 1 to 5 [see Clinical Studies (14) ]. The most common adverse reactions in Studies 201 and 12-230 (≥25% in either study) were 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% in either study) were 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. Study 201 In Study 201, among 25 patients who received DANYELZA in combination with GM-CSF, 12% were exposed for 6 months or longer and none were exposed for greater than one year. Serious adverse reactions occurred in 32% of patients who received DANYELZA in combination with GM-CSF. Serious adverse reactions in more than one patient included anaphylactic reaction (12%) and pain (8%). Permanent discontinuation of DANYELZA due to an adverse reaction occurred in 12% of patients. Adverse reactions resulting in permanent discontinuation of DANYELZA included anaphylactic reaction (8%) and respiratory depression (4%). Dosage interruptions of DANYELZA due to an adverse reaction occurred in 84% of patients. Adverse reactions requiring dosage interruption in > 10% of patients included hypotension and bronchospasm. Table 4 summarizes adverse reactions in Study 201. Table 4. Adverse Reactions (>10%) in Patients with Refractory or Relapsed High-Risk Neuroblastoma in Bone or Bone Marrow Who Received DANYELZA with GM-CSF in Study 201 DANYELZA with GM-CSF Adverse...

Contraindications

4 CONTRAINDICATIONS DANYELZA is contraindicated in patients with a history of severe hypersensitivity reaction to naxitamab-gqgk. Reactions have included anaphylaxis [see Warnings and Precautions (5.1) ]. History of severe hypersensitivity reaction to naxitamab-gqgk. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Based on its mechanism of action, DANYELZA may cause fetal harm when administered to pregnant women [see Clinical Pharmacology (12.1) ]. There are no available data on the use of DANYELZA in pregnant women and no animal reproduction studies have been conducted with DANYELZA. IgG1 monoclonal antibodies are transported across the placenta in a linear fashion as pregnancy progresses, with the largest amount transferred during the third trimester. Advise pregnant women of potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

How Supplied

16 HOW SUPPLIED / STORAGE AND HANDLING DANYELZA (naxitamab-gqgk) injection is a sterile, preservative-free, clear to slightly opalescent and colorless to slightly yellow solution for intravenous infusion supplied as a carton containing one 40mg/10 mL (4 mg/mL) single-dose vial. NDC 73042-201-01 Store DANYELZA vial refrigerated at 2°C to 8°C (36°F to 46°F) in the outer carton to protect from light until time of use.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.