Introduction

Antilipemic agent; angiopoietin-like protein 3 (ANGPTL3) inhibitor.

Uses for Evinacumab (Systemic)

Homozygous Familial Hypercholesterolemia

Used as an adjunct to other LDL-cholesterol (LDL-C) lowering therapies for the treatment of adultx and pediatric patients ≥5 years of age with homozygous familial hypercholesterolemia (HoFH).

Safety and effectiveness not established in patients with other causes of hypercholesterolemia (including heterozygous familial hypercholesterolemia [HeFH]). Effects on cardiovascular morbidity and mortality not determined.

Designated an orphan drug for treatment of HoFH.

Maximally tolerated doses of high-intensity statins are recommended in patients with HoFH in addition to ezetimibe and a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. Evinacumab with or without LDL apheresis is an adjunct option that may be considered if target LDL-C levels are not reached.

Evinacumab (Systemic) Dosage and Administration

General

Pretreatment Screening

• Consider pregnancy testing in females of reproductive potential prior to initiation of evinacumab.

Patient Monitoring

• Assess LDL-C when clinically appropriate. The LDL-C lowering effects of evinacumab can be measured as early as 2 weeks after initiation of treatment.

Administration

Administer by IV infusion (after dilution) through an IV line containing a sterile in-line or add-on, 0.2–5 micron filter. Must dilute commercially available concentrate; discard any unused portionl after preparation.

If a dose is missed, administer the missed dose as soon as possible. Adjust monthly infusion schedule thereafter based on date of last dose administered.

If refrigerated, allow diluted solution to come to room temperature prior to administration.

Do not mix with or administer other medications concomitantly via same infusion line.

May be administered without regard to timing of lipoprotein apheresis.

Slow, interrupt, or discontinue infusion if patient develops any signs of adverse reactions, including infusion or hypersensitivity reactions.

Dilution

Calculate appropriate dose and volume to withdraw from the vial prior to dilution.

Withdraw required volume and transfer into IV infusion bag containing maximum volume of 250 mL of 0.9% sodium chloride injection or 5% dextrose injection to yield a final concentration of 0.5–20 mg/mL based on the patient's body weight. Gently invert to mix solution; do not shake.

Rate of Administration

Administer by IV infusion over 60 minutes through a sterile, in-line or add-on, 0.2–5- micron filter.

Dosage

Pediatric Patients

Homozygous Familial Hypercholesterolemia

IV

≥5 years of age: 15 mg/kg once monthly (every 4 weeks).

Adults

Homozygous Familial Hypercholesterolemia

IV

15 mg/kg once monthly (every 4 weeks).

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Patients

No specific dosage recommendations at this time.

Contraindications

• History of serious hypersensitivity reactions to evinacumab or to any of its excipients.

Warnings/Precautions

Serious Hypersensitivity Reactions

Serious hypersensitivity reactions including anaphylaxis reported. Discontinue infusion if signs or symptoms of serious hypersensitivity occur; treat according to standard-of-care. Monitor until signs and symptoms resolve.

Embryo-fetal Toxicity

Potental for fetal malformations based on animal studies.

Advise females of potential risk to fetus and consider pregnancy testing prior to initiating treatment. Advise females of reproductive potential to use effective contraception throughout treatment with evinacumab and for at least 5 months following last dose.

Immunogenicity

Potential for immunogenicity. One patient receiving evinacumab developed anti-evinacumab antibodies; no effects on the efficacy or plasma concentrations.

Specific Populations

Pregnancy

May cause fetal harm. Consider pregnancy testing prior to initiating evinacumab in females of reproductive potential. Animal studies indicate evinacumab crosses placental barrier. Advise females of reproductive potential to use effective contraception throughout treatment, and for at least 5 months following the last dose of evinacumab. If pregnancy occurs during therapy, call 1-833-385-3392 to report exposure.

Lactation

Not known whether evinacumab is distributed into human milk, affects milk production, or affects breastfed infants. Maternal IgG is known to distribute into human milk. Consider benefits of breastfeeding against potential for adverse effects to breastfed infant, along with mother’s clinical need for evinacumab.

Females and Males of Reproductive Potential

Consider pregnancy testing prior to treatment with evinacumab.

Based on animal data, may cause fetal harm when administered during pregnancy. Advise females of reproductive potential to use effective contraception during treatment and for at least 5 months following the last dose.

Pediatric Use

Safety and efficacy for treatment of HoFH established in pediatric patients ≥5 years of age. Safety profile of evinacumab in pediatric patients 5-11 years of age was similar to safety profile in adults and pediatric patients ≥12 years of age, with the additional adverse reaction of fatigue.

Safety and efficacy not established in pediatric patients <5 years of age.

Geriatric Use

Clinical studies did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently from younger adult patients.

Hepatic Impairment

No data available in hepatic impairment.

Common Adverse Effects

Adverse reactions (≥5%): nasopharyngitis, influenza-like illness, dizziness, rhinorrhea, fatigue, nausea.

Infusion reactions occurred in 7% of patients receiving evinacumab and more frequently than with placebo.

General

Pretreatment Screening

• Consider pregnancy testing in females of reproductive potential prior to initiation of evinacumab.

Patient Monitoring

• Assess LDL-C when clinically appropriate. The LDL-C lowering effects of evinacumab can be measured as early as 2 weeks after initiation of treatment.

Administration

Administer by IV infusion (after dilution) through an IV line containing a sterile in-line or add-on, 0.2–5 micron filter. Must dilute commercially available concentrate; discard any unused portionl after preparation.

If a dose is missed, administer the missed dose as soon as possible. Adjust monthly infusion schedule thereafter based on date of last dose administered.

If refrigerated, allow diluted solution to come to room temperature prior to administration.

Do not mix with or administer other medications concomitantly via same infusion line.

May be administered without regard to timing of lipoprotein apheresis.

Slow, interrupt, or discontinue infusion if patient develops any signs of adverse reactions, including infusion or hypersensitivity reactions.

Dilution

Calculate appropriate dose and volume to withdraw from the vial prior to dilution.

Withdraw required volume and transfer into IV infusion bag containing maximum volume of 250 mL of 0.9% sodium chloride injection or 5% dextrose injection to yield a final concentration of 0.5–20 mg/mL based on the patient's body weight. Gently invert to mix solution; do not shake.

Rate of Administration

Administer by IV infusion over 60 minutes through a sterile, in-line or add-on, 0.2–5- micron filter.

Dosage

Pediatric Patients

Homozygous Familial Hypercholesterolemia

IV

≥5 years of age: 15 mg/kg once monthly (every 4 weeks).

Adults

Homozygous Familial Hypercholesterolemia

IV

15 mg/kg once monthly (every 4 weeks).

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Patients

No specific dosage recommendations at this time.

No formal drug interaction studies performed.

Specific Drugs