Drug Information

Indication:

U.S. FDA APPROVED DRUGS DURING 2020

Sr.No- 46

Name of the Drug- DANYELZA

Active Ingredient - Naxitamab- gqgk

Pharmacological Classification-

To treat high-risk refractory or relapsed neuroblastoma

Date of Approval- 11/25/2020

(Ref- FDA approved List 2020)

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use

DANYELZA safely and effectively.

See full prescribing information for DANYELZA. DANYELZA® (naxitamab-gqgk) injection, for intravenous use

Initial U.S. Approval: 2020

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

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

INDICATIONS AND USAGE-

DANYELZA 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).

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.

Adverse Reaction:

ADVERSE REACTIONS-

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

Contra-Indications:

CONTRAINDICATIONS-

History of severe hypersensitivity reaction to naxitamab-gqgk.

WARNINGS AND PRECAUTIONS-

Neurotoxicity: Peripheral neuropathy, neurological disorders of the eye, and prolonged urinary retention have also occurred. Permanently discontinue as recommended

Hypertension: Monitor blood pressure during and after infusion as recommended. Withhold, reduce infusion rate, or discontinue based on severity.

Embryo-Fetal Toxicity: May cause fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception

Dosages/ Overdosage Etc:

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.

DOSAGE FORMS AND STRENGTHS- Injection: 40 mg/10 mL (4 mg/mL) in a single-dose vial.

Patient Information:

PATIENT COUNSELING INFORMATION

Advise the patient and caregiver to read the FDA-approved patient labeling (Patient Information).

Serious Infusion-Related Reactions- Advise patients and caregivers that DANYELZA can cause serious infusion-related reactions and anaphylaxis and to immediately report any signs or symptoms, such as facial or lip swelling, urticaria, or difficulty breathing, that occur during or following the infusion

Neurotoxicity- Advise patients and caregivers that DANYELZA can cause neurotoxicity, including severe pain, peripheral neuropathy, neurological disorders of the eye, prolonged urinary retention, transverse myelitis, and reverse posterior leukoencephalopathy syndrome.

Advise patients to contact their healthcare provider for any new or worsening neurological symptoms.

Hypertension- Advise patients and caregivers that DANYELZA can cause hypertension and to immediately report signs or symptoms of hypertension.

Embryo-Fetal Toxicity- Advise females of reproductive potential, including pregnant women, of the potential risk to the fetus.

Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy and to use effective contraception during treatment with and for 2 months after the final dose of DANYELZA

Lactation- Advise women not to breastfeed during treatment with DANYELZA and for 2 months after the final dose.

DANYELZA is a trademark of Y-mAbs Therapeutics, Inc. © 2020 Y-mAbs Therapeutics, Inc. – All rights reserved. Manufactured by: Y-mAbs Therapeutics, Inc 230 Park Avenue, Suite 3350 New York, NY 10169 U.S. License No. 2209

Pharmacology/ Pharmacokinetics:

12 CLINICAL PHARMACOLOGY

1 Mechanism of Action- 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.

2. Pharmacodynamics- The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of naxitamab-gqgk have not been fully characterized.

3. Pharmacokinetics- 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.

Specific Populations- Population pharmacokinetic analyses suggest that age (range: 1 to 34 years), sex and race have no clinically important effect on the clearance (CL) 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 naxitamabgqgk exposures at 3 mg/kg/day (9 mg/kg per cycle) for patients with body weight of 30 - 50 kg.

Pregnancy and lactation:

USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary- Based on its mechanism of action, DANYELZA may cause fetal harm when administered to pregnant women.

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.

2. Lactation Risk Summary - There are no data on the presence of naxitamab-gqgk in human milk or its effects on the breastfed child, or on milk production, however, human IgG is present in human milk.

Because of the potential for serious adverse reactions in a breastfed child from DANYELZA, advise women not to breastfeed during treatment and for 2 months after the final dose of DANYELZA

3. Females and Males of Reproductive Potential- DANYELZA may cause fetal harm when administered to a pregnant woman.

Pregnancy Testing- Verify pregnancy status in females of reproductive potential prior to initiating DANYELZA.

Contraception- Females- Advise females of reproductive potential to use effective contraception during treatment and for 2 months after the final dose of DANYELZA.

4. Pediatric Use- The safety and effectiveness of DANYELZA, in combination with GM-CSF for the treatment of relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response or stable disease following prior therapy, have been established in pediatric patients 1 year of age and older.

Safety and effectiveness have not been established in pediatric patients younger than 1 year of age.

5. Geriatric Use- Neuroblastoma is largely a disease of pediatric and young adult patients.

Clinical studies of DANYELZA in combination with GM-CSF did not include patients 65 years of age and older.

46/20. Naxitamab-gqgk- (DANZELY) -(Nov 2020)- To treat high-risk refractory relpased neuroblastoma

Indication

Adverse Reaction

Contra-Indications

Dosages/ Overdosage Etc

Patient Information

Pharmacology/ Pharmacokinetics

Pregnancy and lactation