evinacumab (Rx)

>10%

Nasopharyngitis (16%)

1-10%

Influenzalike illness (7%)

Infusion-related reactions (7%)

Dizziness (6%)

Rhinorrhea (5%)

Nausea (5%)

Pain in extremity (4%)

Asthenia (4%)

Constipation (<3%)

Upper respiratory tract infection (<3%)

Nasal congestion (<3%)

Abdominal pain (<3%)

Serious anaphylaxis (1%)

Frequency Not Defined

Decreased diastolic blood pressure (transient, mild-to-moderate)

Increased heart rate

Contraindications

History of serious hypersensitivity to drug or any of its excipients

Cautions

Serious hypersensitivity reactions, including anaphylaxis, reported; if serious reaction occurs, discontinue infusion and treat according to standard of care

May cause fetal harm based on animal reproduction studies

Pregnancy

Based on animal studies, may cause fetal harm

Consider pregnancy testing in females who may become pregnant before starting treatment

Available human data are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Evinacumab is a human IgG4 monoclonal antibody, and human IgG is known to cross the placental barrier; therefore, evinacumab may potentially transmit from mother to developing fetus

Advise pregnant females of potential fetal risk

If patient becomes pregnant during treatment, report exposure by calling 1-833-385-3392

Animal data

• SC administration to pregnant rabbits during organogenesis resulted in fetal malformations (domed head, hydrocephalus, and flexed limbs) at doses below the maximum recommended human dose
• These malformations were not observed in pregnant rats

Contraception

• Females of reproductive potential should use effective contraception during treatment and for at least 5 months following last dose

Lactation

Data are unavailable regarding presence in human milk or animal milk, effects on breastfed infants, or effects on milk production

Maternal IgG is known to be present in human milk; effects of local gastrointestinal exposure and limited systemic exposure in breastfed infants are unknown

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Recombinant human monoclonal antibody that binds to and inhibits angiopoietin-like 3 (ANGPTL3)

ANGPTL3 inhibits lipoprotein lipase and endothelial lipase, thereby, reducing lipid metabolism; evinacumab inhibits ANGPTL3 and results in increased lipid metabolism, leading to decreased LDL-C, HDL-C, and triglycerides (TG)

Inhibition of ANGPTL3 induces accelerated hydrolysis of very low-density lipoprotein particles by up-regulating clearance pathways; up-regulation of apolipoprotein-B–containing lipoprotein clearance occurs before reaching the size of LDL

Absorption

Steady-state reached after 4 doses

Trough concentration (steady-state): 241 mg/L

Peak plasma concentration (end of infusion): 157 mg/L

Distribution

Vd: 4.8 L

Metabolism

Not characterized

As an IgG4 antibody, expected to be degraded into small peptides and amino acids via catabolic pathways, similar to endogenous IgG

Elimination

Mediated via parallel linear and nonlinear pathways; at high concentrations, elimination primarily through nonsaturable proteolytic pathway; at lower concentrations, nonlinear, saturable ANGPTL3 target-mediated elimination predominates

Half-life: Function of concentrations and is not a constant

Excretion: Not likely to undergo renal excretion

IV Compatability

0.9% NaCl

D5W

IV Preparation

Calculate dose (mg) and total volume (mL) required to determine number of vials required

Visually inspect solution for cloudiness, discoloration, and particulate matter; should appear clear to slightly opalescent, colorless to pale-yellow

Do not administer if solution is cloudy or discolored or contains particulate matter

Withdraw dosage volume from vial(s) and transfer into an IV infusion bag containing maximum volume of 250 mL of 0.9% NaCl or D5W

Mix diluted solution by gentle inversion; do not shake

Final concentration of diluted solution should be 0.5-20 mg/mL depending on patient weight

Administer diluted solution immediately after preparation and discard any unused portion left in vial; if unable to use immediately, may store briefly (see Storage)

IV Administration

If refrigerated, allow diluted solution to come to room temperature before administration

Infuse IV over 60 minutes through an IV line containing a sterile, in-line or add-on, 0.2- to 5-micron filter

Do not mix with other medications or administer other medications concomitantly via the same IV line

Infusion may be slowed, interrupted, or discontinued if signs of adverse reactions occur, including infusion-related reactions or hypersensitivity

May administer without regard to timing of lipoprotein apheresis

Missed dose

• Administer as soon as possible
• Thereafter, schedule monthly from date of last dose

Storage

Does not contain preservative

Do not shake

Do not freeze

Unopened vials

• Refrigerate at 2-8ºC (36-46ºF) in original carton to protect from light

Diluted solution

• Refrigerate at 2-8ºC (36-46ºF) for no more than 24 hr from time of preparation to end of infusion, OR
• Room temperature up to 25ºC (77ºF) for no more than 6 hr from time of preparation to end of infusion