Evkeeza

Drug overview for EVKEEZA (evinacumab-dgnb):

Generic name: evinacumab-dgnb (E-vin-AK-ue-mab)
Drug class: Antihyperlipidemic - Angiopoietin-like 3 (ANGPTL3) Inhibitor
Therapeutic class: Cardiovascular Therapy Agents

Evinacumab-dgnb, an angiopoietin-like protein 3 (ANGPTL3) inhibitor, is an antilipemic agent.

No enhanced Uses information available for this drug.

DRUG IMAGES

EVKEEZA 345 MG/2.3 ML VIAL
EVKEEZA 1,200 MG/8 ML VIAL

The following indications for EVKEEZA (evinacumab-dgnb) have been approved by the FDA:

Indications:
Homozygous familial hypercholesterolemia

Professional Synonyms:
Familial homozygous hypercholesterolemia

Dosing information for EVKEEZA
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
EVKEEZA 1,200 MG/8 ML VIAL	Maintenance	Adults infuse 15 mg/kg over 60 minute(s) by intravenous route every 4 weeks
EVKEEZA 345 MG/2.3 ML VIAL	Maintenance	Adults infuse 15 mg/kg over 60 minute(s) by intravenous route every 4 weeks

The following drug interaction information is available for EVKEEZA (evinacumab-dgnb):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 2 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
IgG Antibodies and Derivatives/Efgartigimod-alfa SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Efgartigimod-alfa binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3) CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of efgartigimod-alfa states that efgartigimod-alfa should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, efgartigimod-alfa should be discontinued.(3) DISCUSSION: Clinical drug interaction studies with efgartigimod-alfa have not been performed. Efgartigimod alfa may decrease concentrations of compounds that bind to the human FcRn.(3)	VYVGART, VYVGART HYTRULO
Pozelimab/IgG Antibodies and Derivatives SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Pozelimab is an IgG4P antibody. Concurrent use of immunoglobulins and other IgG-based antibodies that bind to FcRn may interfere with the FcRn recycling mechanism of pozelimab and decrease systemic exposure of pozelimab.(3) CLINICAL EFFECTS: The levels and effectiveness of pozelimab may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of pozelimab states that concomitant use of intravenous immunoglobulin should avoided with pozelimab. If concomitant use cannot be avoided, monitor patients for worsening signs and symptoms of CD55-deficient protein-losing enteropathy.(3) DISCUSSION: Clinical drug interaction studies with pozelimab have not been performed. Immunoglobulins may interfere with the endosomal FcRn recycling mechanism of monoclonal antibodies like pozelimab and decrease concentrations of pozelimab.(3)	VEOPOZ

Drug Interaction

Drug Names

IgG Antibodies and Derivatives/Efgartigimod-alfa

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Efgartigimod-alfa binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of efgartigimod-alfa states that efgartigimod-alfa should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, efgartigimod-alfa should be discontinued.(3)

DISCUSSION: Clinical drug interaction studies with efgartigimod-alfa have not been performed. Efgartigimod alfa may decrease concentrations of compounds that bind to the human FcRn.(3)

VYVGART, VYVGART HYTRULO

Pozelimab/IgG Antibodies and Derivatives

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Pozelimab is an IgG4P antibody. Concurrent use of immunoglobulins and other IgG-based antibodies that bind to FcRn may interfere with the FcRn recycling mechanism of pozelimab and decrease systemic exposure of pozelimab.(3)

CLINICAL EFFECTS: The levels and effectiveness of pozelimab may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of pozelimab states that concomitant use of intravenous immunoglobulin should avoided with pozelimab. If concomitant use cannot be avoided, monitor patients for worsening signs and symptoms of CD55-deficient protein-losing enteropathy.(3)

DISCUSSION: Clinical drug interaction studies with pozelimab have not been performed. Immunoglobulins may interfere with the endosomal FcRn recycling mechanism of monoclonal antibodies like pozelimab and decrease concentrations of pozelimab.(3)

VEOPOZ

There are 1 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
IgG Antibodies and Derivatives/Rozanolixizumab-noli SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Rozanolixizumab-noli binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3) CLINICAL EFFECTS: The effectiveness of medications that bind to FcRn may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of rozanolixizumab-noli states that concurrent use with medications that bind to the human neonatal Fc receptor (FcRn) should be closely monitored for reduced effectiveness of these medications. If long-term use of such medications is essential for the patient, consider discontinuing rozanolixizumab-noli and use alternative therapies.(3) DISCUSSION: Clinical drug interaction studies with rozanolixizumab-noli have not been performed. Rozanolixizumab-noli may decrease concentrations of compounds that bind to the human FcRn.(3)	RYSTIGGO

Drug Interaction

Drug Names

IgG Antibodies and Derivatives/Rozanolixizumab-noli

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Rozanolixizumab-noli binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medications that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of rozanolixizumab-noli states that concurrent use with medications that bind to the human neonatal Fc receptor (FcRn) should be closely monitored for reduced effectiveness of these medications. If long-term use of such medications is essential for the patient, consider discontinuing rozanolixizumab-noli and use alternative therapies.(3)

DISCUSSION: Clinical drug interaction studies with rozanolixizumab-noli have not been performed. Rozanolixizumab-noli may decrease concentrations of compounds that bind to the human FcRn.(3)

RYSTIGGO

Severe List
Pregnancy

The following adverse reaction information is available for EVKEEZA (evinacumab-dgnb):

Overview
Severe
Less Severe

Adverse reaction overview.

Adverse reactions reported in >=5%of patients receiving evinacumab-dgnb include nasopharyngitis, influenza-like illness, dizziness, rhinorrhea, fatigue, and nausea. Infusion reactionsoccurred in 7% of patients receiving evinacumab, and more frequently with the drug than with placebo. Infusion reactions include infusion site pruritis, pyrexia, muscular weakness, nausea, and nasal congestion.

There are 2 severe adverse reactions.

More Frequent	Less Frequent
None.	Anaphylaxis Hypersensitivity drug reaction

Rare/Very Rare
None.

There are 14 less severe adverse reactions.

More Frequent	Less Frequent
Dizziness Flu-like symptoms Nausea Pharyngitis Rhinorrhea	Acute abdominal pain Constipation Fever General weakness Injection site sequelae Muscle weakness Nasal congestion Pain in extremities Upper respiratory infection

Rare/Very Rare
None.

The following precautions are available for EVKEEZA (evinacumab-dgnb):

Pediatric
Pregnant
Lactation
Geriatric

Safety and efficacy of evinacumab-dgnb as an adjunct to other LDL-C-lowering therapies for the treatment of HoFH have been established in pediatric patients>=5 years of age. Evidence from adequate and well-controlled studies in adults and additional efficacy and safety data in pediatric patients >=5 years of age support this use. The safety profile of evinacumab-dgnb in pediatric patients 5-11 years of age was similar to the safety profile in adults and pediatric patients>=12 years of age, with the additional adverse reaction of fatigue. Safety and efficacy of evinacumab have not been established in pediatric patients with HoFH who are <5 years of age.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

Evinacumab-dgnb

1 Day – 5 Years

Safety and effectiveness not established in pediatric patients age < 5 years old.

Animal data indicate that evinacumab-dgnb may cause fetal harm if used during pregnancy. Human data are inadequate to determine the risk of fetal malformations, miscarriage, and adverse outcomes associated with use of evinacumab during pregnancy. Human immune globulin G (IgG) is known to cross the placenta; therefore, evinacumab, a human IgG4 antibody, has the potential to cross the placental barrier and be transmitted to the developing fetus.

Animal studies indicate that evinacumab crosses the placental barrier. In animal studies, an increase in fetal malformations was observed when evinacumab was administered during organogenesis. If a patient becomes pregnant while on evinacumab, providers should call 1-833-385-3392 to report exposure.

Drug/Drug Class	Severity	Precaution Description	Pregnancy Category Description
Evinacumab-dgnb	D	May cross placenta; animal data suggest toxicity	Positive evidence of human fetal risk based on investigation or marketing information but potential benefits may warrant use of drug in pregnant women despite potential risks.

It is not known whether evinacumab is distributed into human or animal milk. However, maternal IgG is known to be present in human milk. The effects of the drug on the breastfed infant or on the production of milk are not known. The benefits of breastfeeding should be balanced with the potential for adverse effects from evinacumab exposure to the breastfed infant, along with the mother's clinical need for evinacumab.

Precaution Exists
Precaution exists. (No data or inconclusive human data.) Use of this drug by breast feeding mothers should be evaluated carefully.

Drug Name	Excretion Potential	Effect on Infant	Notes
Evinacumab-dgnb	Unknown. It is unknown whether the drug is excreted in human breast milk.	It is not known whether this drug has an adverse effect on the nursing infant. (No data or inconclusive human data)	Insufficient human data available

The manufacturer makes no specific dosage recommendations for geriatric patients. Insufficient numbers of patients >=65 years of age were included in clinical studies of evinacumab to determine whether there are differences in response compared to younger patients.

Homozygous familial hypercholesterolemia
E78.01	Familial hypercholesterolemia