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Evinacumab: Drug information

Evinacumab: Drug information
(For additional information see "Evinacumab: Pediatric drug information" and see "Evinacumab: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Evkeeza
Pharmacologic Category
  • Antilipemic Agent, Angiopoietin-Like Protein 3 (ANGPTL3) Inhibitor;
  • Monoclonal Antibody
Dosing: Adult
Homozygous familial hypercholesterolemia

Homozygous familial hypercholesterolemia: IV: 15 mg/kg every 4 weeks.

Missed dose: Administer as soon as possible, then schedule every 4 weeks from the date of last dose.

Dosing: Kidney Impairment: Adult

Mild to moderate impairment: No dosage adjustment necessary.

Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, dosage adjustment is unlikely to be required as monoclonal antibodies are not known to be renally eliminated.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Pediatric

(For additional information see "Evinacumab: Pediatric drug information")

Homozygous familial hypercholesterolemia, adjunct

Homozygous familial hypercholesterolemia, adjunct: Children ≥12 years and Adolescents: IV: 15 mg/kg/dose every 4 weeks; use in combination with other low-density lipoprotein-cholesterol (LDL-C) lowering therapies.

Dosing: Kidney Impairment: Pediatric

Altered kidney function: Children ≥12 years and Adolescents:

Mild to moderate: No dosage adjustment necessary. Observed trough concentrations were comparable between patients with mild to moderate renal function and patients with normal renal function.

Severe: There are no dosage adjustments are provided in the manufacturer's labeling (has not been studied); dosage adjustment is unlikely to be required as monoclonal antibodies are not known to be renally eliminated.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments are provided in the manufacturer's labeling.

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Evkeeza: Evinacumab-dgnb 1200 mg/8 mL (150 mg/mL) (8 mL); Evinacumab-dgnb 345 mg/2.3 mL (150 mg/mL) (2.3 mL) [contains polysorbate 80]

Generic Equivalent Available: US

No

Administration: Adult

IV: Do not shake. If refrigerated, allow diluted solution to come to room temperature prior to administration; otherwise administer immediately after preparation. Administer IV infusion over 60 minutes through an IV line containing a sterile, in-line or add-on, 0.2-micron to 5-micron filter. May administer without regard to timing of lipoprotein apheresis. Rate of infusion may be slowed, interrupted, or discontinued if patient develops any adverse reactions, including infusion or hypersensitivity reactions.

Administration: Pediatric

Parenteral: IV: Must be diluted prior to administration. If diluted solution is refrigerated following preparation, allow solution to come to room temperature prior to administration. Administer IV over 60 minutes using an inline or add on 0.2-micron to 5-micron filter. Slow, interrupt, or discontinue infusion and treat as appropriate if patient develops adverse reaction or infusion reaction (eg, infusion site pruritus, pyrexia, muscular weakness, nausea, nasal congestion). Discontinue and provide emergency care if serious or life-threatening hypersensitivity reaction occurs.

Missed dose: If dose is missed, administer as soon as possible and reschedule subsequent dose from date of last dose.

Use: Labeled Indications

Homozygous familial hypercholesterolemia: Adjunct to other low-density lipoprotein (LDL)-lowering therapies for the treatment of homozygous familial hypercholesterolemia (HoFH) in adults and pediatric patients ≥12 years of age.

Limitations of use: Safety and effectiveness have not been established in patients with other causes of hypercholesterolemia, including those with heterozygous familial hypercholesterolemia (HeFH).

Adverse Reactions (Significant): Considerations
Hypersensitivity reactions

Severe hypersensitivity reactions, including anaphylaxis, have occurred (Ref).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%: Respiratory: Nasopharyngitis (16%)

1% to 10%:

Gastrointestinal: Abdominal pain (<3%), constipation (<3%), nausea (5%)

Hypersensitivity: Anaphylaxis (1%) (table 1), severe hypersensitivity reaction

Evinacumab: Adverse Reaction: Anaphylaxis

Drug (Evinacumab)

Placebo

Number of Patients (Evinacumab)

Number of Patients (Placebo)

1%

0%

81

54

Nervous system: Dizziness (6%)

Neuromuscular & skeletal: Asthenia (4%), limb pain (4%)

Respiratory: Flu-like symptoms (7%), nasal congestion (<3%), rhinorrhea (5%), upper respiratory tract infection (<3%)

Miscellaneous: Infusion related reaction (7%; including injection site pruritus, fever, and myasthenia)

Frequency not defined: Cardiovascular: Decreased diastolic blood pressure (transient), increased heart rate (transient)

Contraindications

Serious hypersensitivity (eg, anaphylaxis) to evinacumab or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reactions: Serious hypersensitivity reactions, including anaphylaxis, have occurred. Discontinue treatment and initiate supportive treatment in patients who develop serious allergic reaction; monitor until symptoms resolve.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Reproductive Considerations

Evaluate pregnancy status prior to use in patients who may become pregnant. Patients who may become pregnant should use effective contraception during therapy and for at least 5 months after the last evinacumab dose.

Pregnancy Considerations

Based on data from animal reproduction studies, in utero exposure to evinacumab may cause fetal harm.

Evinacumab is a humanized monoclonal antibody (IgG4). Placental transfer of human IgG is dependent upon the IgG subclass, maternal serum concentrations, newborn birth weight, and GA, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).

Breastfeeding Considerations

It is not known if evinacumab is present in breast milk; however, evinacumab is a humanized monoclonal antibody (IgG4); maternal IgG is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.

Monitoring Parameters

Assess low-density lipoprotein-cholesterol (LDL-C) when clinically appropriate; LDL lowering may be measured as early as 2 weeks after initiating therapy; signs/symptoms of hypersensitivity reactions; rule out pregnancy prior to therapy initiation.

Mechanism of Action

Evinacumab-dgnb is a recombinant human monoclonal antibody that binds to and inhibits angiopoietin-like protein 3 (ANGPTL3). ANGPTL3 inhibits lipoprotein lipase (LPL) and endothelial lipase (EL). ANGPTL3 inhibition by evinacumab results in increased lipid metabolism, leading to decreased low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and triglycerides (TG). Evinacumab-dgnb reduces LDL-C independent of the presence of LDL receptor by promoting very low-density lipoprotein processing and clearance upstream of LDL formation. Evinacumab-dgnb blockade of ANGPTL3 lowers TG and HDL-C by rescuing LPL and EL activities, respectively.

Pharmacokinetics

Distribution: Vd: ~4.8 L.

Metabolism: Expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.

Half-life elimination: Function of evinacumab serum concentration and is not a constant.

Time to peak: End of infusion: 157 mg/L.

Excretion: Not likely to undergo renal excretion.

Pricing: US

Solution (Evkeeza Intravenous)

345MG/2.3ML (per mL): $5,850.00

1200 mg/8 mL (per mL): $5,850.00

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

  1. Evkeeza (evinacumab) [prescribing information]. Tarrytown, NY: Regeneron Pharmaceuticals Inc; February 2021.
  2. Markham A. Evinacumab: first approval. Drugs. 2021;10.1007/s40265-021-01516-y. doi:10.1007/s40265-021-01516-y [PubMed 34003472]
  3. Palmeira P, Quinello C, Silveira-Lessa AL, Zago CA, Carneiro-Sampaio M. IgG placental transfer in healthy and pathological pregnancies. Clin DevImmunol. 2012;2012:985646. doi:10.1155/2012/985646 [PubMed 22235228]
  4. Pentsuk N, van der Laan JW. An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res B Dev Reprod Toxicol. 2009;86(4):328-344. doi:10.1002/bdrb.20201 [PubMed 19626656]
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