Evkeeza evinacumab 150 mg/mL Injection, Solution, Concentrate, 1 vial
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Angiopoietin-like 3 Inhibitor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Evinacumab-dgnb injection is used to lower cholesterol in patients with homozygous familial hypercholesterolemia (HoFH; an inherited condition in which cholesterol cannot be removed from the body normally). Evinacumab-dgnb is in a class of medications called angiopoietin-like protein 3 (ANGPTL3) inhibitor monoclonal antibodies. It works by decreasing the production of cholesterol and increasing the breakdown of cholesterol and other fatty substances in the body. Accumulation of cholesterol and fats along the walls of your arteries (a process known as atherosclerosis) decreases blood flow and,...
Read the full MedlinePlus article ↗Patient education
Supplement & herbal interactions
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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14.75 mg / 1 mL
UNII F7LTH1E20Y
Arginine hydrochloride is an amino acid salt used as a buffer and pH adjuster in medicines. It helps maintain the correct acidity level to keep the drug stable and effective.
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0.74 mg / 1 mL
UNII 4QD397987E
An amino acid used as a buffer and stabilizer in medications. It helps maintain the pH balance and protects the active drug from breaking down during storage and use.
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1.1 mg / 1 mL
UNII X573657P6P
Histidine monohydrochloride monohydrate is an amino acid salt used as a buffer in medicines. It helps maintain the proper acidity level of liquid formulations to keep the drug stable and effective.
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1 mg / 1 mL
UNII 6OZP39ZG8H
Polysorbate 80 is a synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together in medications and improves how the product disperses in the body.
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30 mg / 1 mL
UNII 9DLQ4CIU6V
Proline is an amino acid used in pharmaceutical formulations as a bulking agent and stabilizer. It helps maintain product stability and can improve the texture or consistency of medicines, particularly in powders and freeze-dried products.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
6 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $5,452.49 | $12,540.73 / 2.3 ml |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J1305 | $197.633 / J1305 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Evkeeza 150 mg/mLthis 61755-0013-01 | Regeneron | 1 vial | — | — | Discontinued | — |
| Evkeeza 150 mg/mL 61755-0010-01 | Regeneron | 1 vial | — | — | Discontinued | — |
Where does this data come from?
⏳ Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.
🛈 What do these terms mean?
- Biologic patent
- A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
- Reference-product exclusivity
- A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
- Interchangeable exclusivity
- The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
- Earliest biosimilar (LOE)
- The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.
Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.
| Code | What it grants | Expires |
|---|---|---|
| RefProduct | Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date | Feb 11, 2033 |
Is there a biosimilar for EVKEEZA 345 MG/2.3 ML VIAL?
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Can a biosimilar launch before the last patent expires?
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 61755-0013-01 You're viewing this | 1 VIAL, SINGLE-USE in 1 CARTON (61755-013-01) / 2.3 mL in 1 VIAL, SINGLE-USE | 2021-02-11 | Inactivated by FDA |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | ✓ Available |
Questions about this listing
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE EVKEEZA is indicated as an adjunct to diet and exercise and other low-density lipoprotein-cholesterol (LDL-C) lowering therapies to reduce LDL-C in adults and pediatric patients, aged 1 year and older, with homozygous familial hypercholesterolemia (HoFH). EVKEEZA is an angiopoietin-like 3 (ANGPTL3) inhibitor indicated as an adjunct to diet and exercise and other low-density lipoprotein-cholesterol (LDL-C) lowering therapies to reduce LDL-C in adults and pediatric patients, aged 1 year and older, with homozygous familial hypercholesterolemia (HoFH).
( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION The recommended dosage of EVKEEZA is 15 mg/kg administered by intravenous (IV) infusion once monthly (every 4 weeks). ( 2.1 ) See the Full Prescribing Information for preparation instructions for the intravenous infusion. ( 2.2 ) Administer the diluted solution via IV infusion over 60 minutes through an IV line containing a sterile, in-line or add-on, 0.2-micron to 5-micron filter.
( 2.3 ) Do not mix other medications with EVKEEZA or administer other medications concomitantly via the same infusion line. ( 2.3 ) The rate of infusion may be slowed, interrupted or discontinued if the patient develops any signs of adverse reactions, including infusion or hypersensitivity reactions. ( 2.3 )
2.1Recommended Dosage The recommended dosage of EVKEEZA is 15 mg/kg administered by intravenous (IV) infusion over 60 minutes once monthly (every 4 weeks). If a dosage of EVKEEZA is missed, administer as soon as possible. Thereafter, EVKEEZA should be scheduled monthly from the date of the last dosage. Assess LDL-C when clinically appropriate. The LDL-lowering effect of EVKEEZA may be measured as early as 2 weeks after initiation.
2.2Preparation Instructions for Intravenous Infusion Calculate the dosage (mg), total volume (mL) of EVKEEZA required, and the number of vials required based on the patient's current body weight. Visually inspect the solution for cloudiness, discoloration, and particulate matter prior to administration. EVKEEZA is a clear to slightly opalescent, colorless to pale-yellow solution.
Do not administer if the solution is cloudy, discolored, or contains particulate matter. EVKEEZA is supplied as single-dose vials and does not contain a preservative. Prepare the diluted infusion using aseptic technique.
Do not shake the vial. Withdraw the required volume from the vial(s) of EVKEEZA and transfer into an IV infusion bag of 0.9% Sodium Chloride Injection or 5% Dextrose Injection. Discard any unused portion left in the vials.
Mix the diluted solution by gentle inversion; do not shake. Maximum diluent volume by patient weight is summarized in Table 1. Table 1: Maximum Diluent Volume by Patient Weight Patient Weight Maximum Diluent Volume 3 kg to less than 26 kg 5 mL/kg 26 kg to less than 45 kg 150 mL 45 kg and greater 250 mL The final concentration of the diluted solution should be between 0.5 mg/mL and 20 mg/mL depending on the patient's current body weight.
Administer the diluted solution immediately after preparation and discard any unused portion left in the vial. If not administered immediately, store the diluted solution refrigerated at 2 °C to 8 °C (36 °F to 46 °F) for no more than 24 hours from the time of preparation OR at room temperature up to 25 °C (77 °F) for no more than 6 hours from the time of preparation to the end of the infusion. Do not freeze the diluted solution.
2.3Administration Instructions for Intravenous Infusion If refrigerated, allow the diluted solution to come to room temperature prior to administration. Administer EVKEEZA diluted solution via IV infusion through an IV line containing a sterile, in-line or add-on, 0.2-micron to 5-micron filter over 60 minutes. Do not mix other medications with EVKEEZA or administer other medications concomitantly via the same infusion line.
The rate of infusion may be slowed, interrupted or discontinued if the patient develops any signs of adverse reactions, including infusion or hypersensitivity reactions [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ]. EVKEEZA can be administered without regard to the timing of lipoprotein apheresis.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS EVKEEZA is a clear to slightly opalescent, colorless to pale yellow solution available as follows: Injection: 345 mg/2.3 mL (150 mg/mL) and 1,200 mg/8 mL (150 mg/mL) in single-dose vials. Injection: 345 mg/2.3 mL (150 mg/mL) and 1,200 mg/8 mL (150 mg/mL) solution in single-dose vials. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS EVKEEZA is contraindicated in patients with a history of serious hypersensitivity reaction to evinacumab-dgnb or to any of the excipients in EVKEEZA. Serious hypersensitivity reactions, including anaphylaxis, have occurred [see Warnings and Precautions (5.1) ]. History of serious hypersensitivity reactions to evinacumab-dgnb or to any of the excipients in EVKEEZA. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Serious Hypersensitivity Reactions : Have occurred with EVKEEZA in clinical trials. If a serious hypersensitivity reaction occurs, discontinue EVKEEZA, treat according to standard-of-care and monitor until signs and symptoms resolve. ( 5.1 ) Embryo-Fetal Toxicity : EVKEEZA may cause fetal harm based on animal studies.
Advise patients who may become pregnant of the risk to a fetus. Consider obtaining a pregnancy test prior to initiating treatment with EVKEEZA. Advise patients who may become pregnant to use contraception during treatment and for at least 5 months following the last dosage.
( 5.2 , 8.1 , 8.3 )
5.1Serious Hypersensitivity Reactions Serious hypersensitivity reactions, including anaphylaxis, have occurred with EVKEEZA [see Adverse Reactions (6.1) ] . If signs or symptoms of serious hypersensitivity reactions occur, discontinue EVKEEZA infusion, treat according to the standard-of-care, and monitor until signs and symptoms resolve. EVKEEZA is contraindicated in patients with a history of serious hypersensitivity reaction to evinacumab-dgnb.
5.2Embryo-Fetal Toxicity Based on the findings in animal reproduction studies, EVKEEZA may cause fetal harm when administered to pregnant patients. Administration of evinacumab-dgnb to rabbits during organogenesis caused increases in fetal malformations at doses below the human exposure. Advise patients who may become pregnant of the risk to a fetus.
Consider obtaining a pregnancy test prior to initiating treatment with EVKEEZA. Advise patients who may become pregnant to use effective contraception during treatment with EVKEEZA and for at least 5 months following the last dosage of EVKEEZA [see Use in Specific Populations (8.1 , 8.3) ] .
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] Common adverse reactions (≥5%) were nasopharyngitis, influenza-like illness, dizziness, rhinorrhea, nausea, and fatigue. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Regeneron at 1-833-385-3392 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions in Adult and Pediatric Patients (aged 12 to 17 years) with HoFH Safety data are based on pooled results from two randomized, double-blind, placebo-controlled trials that included 81 patients treated with EVKEEZA.
The mean age of EVKEEZA-treated patients was 48 years (range: 15 to 75 years); 52% were females; 5% were Hispanic; 82% were White, 7% Asian, 3% Black or African American, and 9% other races. Forty-four (54%) EVKEEZA-treated patients had HoFH. Patients received EVKEEZA as add-on therapy to other lipid-lowering therapies, including maximally tolerated statin, ezetimibe, proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors, lomitapide, and apheresis.
Adverse reactions led to discontinuation of treatment in 1 (2%) patient who received placebo, and 2 (2%) patients treated with EVKEEZA, including 1 case of anaphylaxis. The most common adverse reactions (reported in greater than 3% of EVKEEZA-treated patients and more frequently than in placebo) are shown in Table 2. Table 2: Adverse Reactions Occurring in >3% of Adult and Pediatric Patients Aged 12 to 17 Years Treated with EVKEEZA and Greater than Placebo in 24-Week, Pooled, Placebo-Controlled Trials Adverse Reactions Placebo (N = 54) % EVKEEZA (N = 81) % Nasopharyngitis 13 16 Influenza like illness 6 7 Dizziness 0 6 Rhinorrhea 0 5 Nausea 2 5 Pain in extremity 0 4 Asthenia 0 4 Other adverse reactions occurring in less than 3% of patients treated with EVKEEZA and greater than placebo included constipation, upper respiratory tract infection, nasal congestion, and abdominal pain.
Transient, mild to moderate decreases in diastolic blood pressure and increases in heart rate occurred in clinical trials of EVKEEZA infusion but did not require intervention and resolved post-infusion. Serious Hypersensitivity Reactions Anaphylaxis was reported in 0% patients who received placebo and 1 (1%) patient treated with EVKEEZA. Infusion Reactions Infusion reactions were reported in 2 (4%) patients who received placebo and 6 (7%) patients treated with EVKEEZA.
The following infusion reactions occurred in EVKEEZA-treated patients: infusion site pruritus, pyrexia, muscular weakness, nausea, and nasal congestion. Adverse Reactions in Pediatric Patients (aged 5 to 11 years) with HoFH Safety data are based on pooled results from a three-part, open-label trial in 20 pediatric patients with HoFH (aged 5 to 11 years) with a median treatment duration of 50 weeks. Part A was a trial of 6 patients who received a single intravenous dose of EVKEEZA 15 mg/kg to determine the dosage for the rest of the trial.
Part B was a single-arm, 24-week trial of EVKEEZA 15 mg/kg given intravenously every 4 weeks in 14 unique patients [see Clinical Studies (14) ]. Part C was a 48-week extension trial of EVKEEZA 15 mg/kg given intravenously every 4 weeks that consisted of 20 patients who entered directly from Parts A or B. The mean age was 9 years (range: 5 to 11 years); 60% females; 70% White, 10% Asian, 5% Black or African American, 5% American Indian or Alaska Native, and 10% other races.
The safety profile of EVKEEZA observed in these patients was consistent with the safety profile observed in adults and pediatric patients aged 12 years and older, with the additi…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary Based on data from animal reproduction studies, EVKEEZA may cause fetal harm when administered to pregnant patients. Available human data are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Evinacumab-dgnb is a human IgG4 monoclonal antibody [see Description (11) ], and human IgG is known to cross the placental barrier; therefore, evinacumab-dgnb has the potential to be transmitted from the mother to the developing fetus.
Subcutaneous administration of evinacumab-dgnb to pregnant rabbits during the period of organogenesis resulted in fetal malformations (domed head, hydrocephalus, and flexed limbs) at doses below the maximum recommended human dose (MRHD). No adverse embryofetal effects were observed with subcutaneous administration of evinacumab-dgnb to pregnant rats during the period of organogenesis at doses below the MRHD. Measurable evinacumab-dgnb serum concentrations were observed in fetal rabbit and rat sera at birth, indicating that evinacumab-dgnb, like other IgG antibodies, crosses the placental barrier (see Data ).
Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
If a patient becomes pregnant while receiving EVKEEZA, healthcare providers should report EVKEEZA exposure by calling 1-833-385-3392. Data Animal Data In an embryo-fetal development study in pregnant rabbits, evinacumab-dgnb was administered subcutaneously at doses of 1, 5, 10 and 30 mg/kg every 3 days (Q3D) during the period of organogenesis from gestation day 7 to day 19. Evinacumab-dgnb was teratogenic in rabbits, causing domed head, dilation of the lateral and third ventricles of the brain, and flexed fore/hind paws at maternal evinacumab-dgnb exposures below human exposure at the MRHD of 15 mg/kg every 4 weeks, based on AUC.
Other fetal malformations, consisting of irregular and abnormal ossification in the skull, palate, and metacarpal, and enlarged anterior and/or posterior fontanelles occurred and were consistent with significant maternal toxicity (including early deaths due to abortion and premature delivery at all doses, reduction in maternal body weight gains, and reduced maternal food consumption). Increased incidences of post-implantation losses, resorptions (total, early, and late), and decreased fetal body weight were also consistent with maternal toxicity.
Evinacumab-dgnb was present in the sera of fetuses born from mothers at 10 and 30 mg/kg/Q3D at levels higher than in maternal serum. In an embryo-fetal development study in pregnant rats, evinacumab-dgnb was administered subcutaneously at doses of 5, 10, 30 and 100 mg/kg/Q3D during the period of organogenesis from gestation day 6 to day 18. Maternal exposures to evinacumab-dgnb were below the human exposure measured at the MRHD.
Evinacumab-dgnb resulted in unexplained maternal deaths at 100 mg/kg/Q3D. Evinacumab-dgnb crossed the placenta and was present at ratios (C Fetal /C Maternal ) ranging from 0.42 to 0.65. No adverse effects on embryofetal development were observed at any dose.
In a combined fertility, embryofetal, and pre- and postnatal development study, female rats were administered evinacumab-dgnb via subcutaneous injection at doses of 30 and 100 mg/kg/Q3D beginning 2 weeks prior to mating and continuing to gestation day 21 or lactation day 21. Mean maternal systemic exposures were below the human exposure at the MRHD throughout the study. No maternal or developmental toxicity was observed.
8.2Lactation Risk Summary There are no data on the presence of evinacumab-dgnb in human milk or animal milk, the effects on the breastfed infant, or the effects on milk prod…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on data from animal reproduction studies, EVKEEZA may cause fetal harm when administered to pregnant patients. Available human data are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Evinacumab-dgnb is a human IgG4 monoclonal antibody [see Description (11) ], and human IgG is known to cross the placental barrier; therefore, evinacumab-dgnb has the potential to be transmitted from the mother to the developing fetus.
Subcutaneous administration of evinacumab-dgnb to pregnant rabbits during the period of organogenesis resulted in fetal malformations (domed head, hydrocephalus, and flexed limbs) at doses below the maximum recommended human dose (MRHD). No adverse embryofetal effects were observed with subcutaneous administration of evinacumab-dgnb to pregnant rats during the period of organogenesis at doses below the MRHD. Measurable evinacumab-dgnb serum concentrations were observed in fetal rabbit and rat sera at birth, indicating that evinacumab-dgnb, like other IgG antibodies, crosses the placental barrier (see Data ).
Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
If a patient becomes pregnant while receiving EVKEEZA, healthcare providers should report EVKEEZA exposure by calling 1-833-385-3392. Data Animal Data In an embryo-fetal development study in pregnant rabbits, evinacumab-dgnb was administered subcutaneously at doses of 1, 5, 10 and 30 mg/kg every 3 days (Q3D) during the period of organogenesis from gestation day 7 to day 19. Evinacumab-dgnb was teratogenic in rabbits, causing domed head, dilation of the lateral and third ventricles of the brain, and flexed fore/hind paws at maternal evinacumab-dgnb exposures below human exposure at the MRHD of 15 mg/kg every 4 weeks, based on AUC.
Other fetal malformations, consisting of irregular and abnormal ossification in the skull, palate, and metacarpal, and enlarged anterior and/or posterior fontanelles occurred and were consistent with significant maternal toxicity (including early deaths due to abortion and premature delivery at all doses, reduction in maternal body weight gains, and reduced maternal food consumption). Increased incidences of post-implantation losses, resorptions (total, early, and late), and decreased fetal body weight were also consistent with maternal toxicity.
Evinacumab-dgnb was present in the sera of fetuses born from mothers at 10 and 30 mg/kg/Q3D at levels higher than in maternal serum. In an embryo-fetal development study in pregnant rats, evinacumab-dgnb was administered subcutaneously at doses of 5, 10, 30 and 100 mg/kg/Q3D during the period of organogenesis from gestation day 6 to day 18. Maternal exposures to evinacumab-dgnb were below the human exposure measured at the MRHD.
Evinacumab-dgnb resulted in unexplained maternal deaths at 100 mg/kg/Q3D. Evinacumab-dgnb crossed the placenta and was present at ratios (C Fetal /C Maternal ) ranging from 0.42 to 0.65. No adverse effects on embryofetal development were observed at any dose.
In a combined fertility, embryofetal, and pre- and postnatal development study, female rats were administered evinacumab-dgnb via subcutaneous injection at doses of 30 and 100 mg/kg/Q3D beginning 2 weeks prior to mating and continuing to gestation day 21 or lactation day 21. Mean maternal systemic exposures were below the human exposure at the MRHD throughout the study. No maternal or developmental toxicity was observed.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of EVKEEZA as an adjunct to other LDL-C-lowering therapies for the treatment of HoFH have been established in pediatric patients aged 1 year and older. Use of EVKEEZA for this indication is supported by evidence from adequate and well-controlled trials in adults with additional pharmacokinetic, efficacy, and safety data in pediatric patients aged 1 year and older [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) and Clinical Studies (14) ] . The safety profile of EVKEEZA in pediatric patients aged 1 to 11 years was similar to the safety profile in adults and pediatric patients aged 12 years and older, with the additional adverse reaction of fatigue in patients aged 5 to 11 years [see Adverse Reactions (6.1) ].
The safety and effectiveness of EVKEEZA have not been established in pediatric patients younger than 1 year of age.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of EVKEEZA did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Evinacumab-dgnb is a recombinant human monoclonal antibody that binds to and inhibits ANGPTL3. ANGPTL3 is a member of the angiopoietin-like protein family that is expressed primarily in the liver and plays a role in the regulation of lipid metabolism by inhibiting lipoprotein lipase (LPL) and endothelial lipase (EL). Evinacumab-dgnb inhibition of ANGPTL3 leads to reduction in LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG).
Evinacumab-dgnb reduces LDL-C independent of the presence of LDL receptor (LDLR) by promoting very low-density lipoprotein (VLDL) processing and clearance upstream of LDL formation. Evinacumab-dgnb blockade of ANGPTL3 lowers TG and HDL-C by rescuing LPL and EL activities, respectively.
12.2Pharmacodynamics Administration of evinacumab-dgnb in patients with HoFH resulted in reductions in LDL-C, total cholesterol (TC), HDL-C, apolipoprotein B and TG [see Clinical Studies (14) ].
12.3Pharmacokinetics The pharmacokinetic parameters described in this section are presented following administration of evinacumab-dgnb 15 mg/kg intravenously every 4 weeks, unless otherwise specified. Steady-state is reached after 4 doses, and the accumulation ratio is 2. According to population pharmacokinetic modeling, the mean (standard deviation) steady-state trough concentration is 266 (120) mg/L in adult patients, whereas the mean (standard deviation) C max at the end of infusion is 718 (183) mg/L in adult patients.
Due to non-linear clearance, a 4.3-fold increase in area under the concentration-time curve at steady-state (AUC tau.ss ) for a 3-fold increase in evinacumab-dgnb dose up to 15 mg/kg IV every 4 weeks was predicted in patients with HoFH. Distribution The steady-state volume of distribution estimated via population pharmacokinetic analysis was approximately
4.7L in adult patients. Elimination Evinacumab-dgnb elimination is mediated via parallel linear and non-linear pathways. At higher concentrations, evinacumab-dgnb elimination is primarily through a non-saturable proteolytic pathway, whereas at lower concentrations, the non-linear, saturable ANGPTL3 target-mediated elimination predominates.
The elimination half-life is a function of serum evinacumab-dgnb concentrations and is not a constant. Based on a population pharmacokinetic analysis, the median time for serum evinacumab-dgnb concentrations to decrease below the lower limit of quantitation (78 ng/mL) is approximately 20 weeks after the last steady-state dose of 15 mg/kg IV every 4 weeks. Metabolism The exact pathway through which evinacumab-dgnb is metabolized has not been characterized.
As a human monoclonal IgG4 antibody, evinacumab-dgnb is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG. Excretion Evinacumab-dgnb, a monoclonal antibody, is not likely to undergo renal excretion. Specific Populations A population PK analysis conducted on data from 183 healthy subjects and 139 patients with HoFH suggests that the following factors have no clinically significant effect on the exposure of evinacumab-dgnb: age (5 to 75 years), gender, body weight (20 to 152 kg), and race (White, Asian, Black or African American, American Indian or Alaska Native, and other races).
Pediatric Patients Fourteen (14) patients aged 12 to less than 18 years with HoFH received evinacumab-dgnb at 15 mg/kg IV every 4 weeks. Steady-state trough and end-of-infusion concentrations were within the range observed in adult patients. Twenty (20) patients aged 5 to less than 12 years with HoFH received evinacumab-dgnb at 15 mg/kg IV every 4 weeks.
According to population pharmacokinetic modeling, the mean (standard deviation) steady-state trough concentration is 160 (57.6) mg/L in pediatric patients, whereas the mean (standard deviation) C max at the end of infusion is 419 (99.4) mg/L in pediatric patients. Steady-state trough and end-of-infusion co…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Evinacumab-dgnb is a recombinant human monoclonal antibody that binds to and inhibits ANGPTL3. ANGPTL3 is a member of the angiopoietin-like protein family that is expressed primarily in the liver and plays a role in the regulation of lipid metabolism by inhibiting lipoprotein lipase (LPL) and endothelial lipase (EL). Evinacumab-dgnb inhibition of ANGPTL3 leads to reduction in LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG).
Evinacumab-dgnb reduces LDL-C independent of the presence of LDL receptor (LDLR) by promoting very low-density lipoprotein (VLDL) processing and clearance upstream of LDL formation. Evinacumab-dgnb blockade of ANGPTL3 lowers TG and HDL-C by rescuing LPL and EL activities, respectively.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING EVKEEZA (evinacumab-dgnb) injection is a clear to slightly opalescent, colorless to pale yellow solution. It is supplied as one single-dose vial per carton. 345 mg/2.3 mL (150 mg/mL) NDC 61755-013-01 1,200 mg/8 mL (150 mg/mL) NDC 61755-010-01 Storage Store in a refrigerator at 2 °C to 8 °C (36 °F to 46 °F).
Store the vial in the original carton to protect from light. Do not freeze. Do not shake.
EVKEEZA does not contain a preservative. If not used immediately, store the diluted solution refrigerated at 2 °C to 8 °C (36 °F to 46 °F) for no more than 24 hours from the time of preparation OR at room temperature up to 25 °C (77 °F) for no more than 6 hours from the time of infusion preparation to the end of the infusion [see Dosage and Administration (2.2) ].
📦 Storage and Handling ▾
Storage Store in a refrigerator at 2 °C to 8 °C (36 °F to 46 °F). Store the vial in the original carton to protect from light. Do not freeze.
Do not shake. EVKEEZA does not contain a preservative. If not used immediately, store the diluted solution refrigerated at 2 °C to 8 °C (36 °F to 46 °F) for no more than 24 hours from the time of preparation OR at room temperature up to 25 °C (77 °F) for no more than 6 hours from the time of infusion preparation to the end of the infusion [see Dosage and Administration (2.2) ].
📋 Description ▾
11 DESCRIPTION Evinacumab-dgnb is an angiopoietin-like protein 3 (ANGPTL3) inhibitor monoclonal antibody (IgG4 isotype) produced by recombinant DNA technology in Chinese hamster ovary (CHO) cell suspension culture. Evinacumab-dgnb has an approximate molecular weight of 146 kDa. EVKEEZA (evinacumab-dgnb) injection is a sterile, preservative-free solution for intravenous use.
The solution is clear to slightly opalescent, colorless to pale-yellow, and free from visible particles. Each vial contains 345 mg/2.3 mL or 1,200 mg/8 mL. Each mL contains 150 mg of evinacumab-dgnb, and L-arginine hydrochloride (14.8 mg), L-histidine (0.74 mg), L-histidine monohydrochloride monohydrate (1.1 mg), L-proline (30 mg), polysorbate 80 (1 mg) and Water for Injection, USP.
The pH is 6.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Hypersensitivity Reactions Inform patients that hypersensitivity reactions have occurred with EVKEEZA. Advise patients to contact their healthcare provider immediately if they experience signs or symptoms of a hypersensitivity reaction [see Warnings and Precautions (5.1) ] .
Embryofetal Toxicity Advise pregnant patients and patients that may become pregnant of the potential risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy. Advise patients who may become pregnant to use effective contraception during treatment with EVKEEZA and for 5 months after the final dosage. Encourage patients who become pregnant to report their pregnancy to 1-833-385-3392 [see Warnings and Precautions (5.2) and Use in Specific Populations (8.1 , 8.3) ].