BRIEF SUMMARY

EVINACUMAB-dgnb-(FEB 2021)

Indn-   For the treatment of homozygous familial                                                                        hyercholesterolemia   

Comp- Injection: 345 mg/2.3 mL (150 mg/mL) and 1,200 mg/8 mL (150 mg/mL) solution in single-dose vials.    recommended dose  is 15 mg/kg administered by intravenous (IV) infusion once monthly (every 4 weeks)       

ADR- Common adverse reactions were nasopharyngitis, influenza-like illness, dizziness, rhinorrhea, and nausea

CI-  History of serious hypersensitivity reactions to evinacumab-dgnb or to any of the excipients 

WARNINGS-

 • Serious Hypersensitivity Reactions:  If a serious hypersensitivity reaction occurs, discontinue  treat according to standard-of-care and monitor until signs and symptoms resolve.

 • Embryo-Fetal Toxicity:  may cause fetal harm based on animal studies. Advise patients who may become pregnant of the risk to a fetus.

 Advise patients who may become pregnant to use contraception during treatment and for at least 5 months following the last dose.

Pat inform-

Hypersensitivity Reactions-                                                                                           Inform patients that hypersensitivity reactions have occurred with the product

Advise patients to contact their healthcare provider immediately if they experience signs or symptoms of a hypersensitivity reaction 

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.

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U.S. FDA APPROVED DRUGS SURING 2021                                          

Serial No 6

Name of the Drug-    EVKEEZA

Active Ingredient -     Evinacumab-dgnb

Pharmacological Classification-   For the treatment of homozygous familial                                                                        hyercholesterolemia          

Date of Approval-          2/11/2021

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use                          EVKEEZA safely and effectively.                                                                                     See full prescribing information for EVKEEZA. EVKEEZA™ (evinacumab-dgnb) injection, for intravenous use

Initial U.S. Approval: 2021

INDICATIONS AND USAGE

 EVKEEZA is an ANGPTL3 (angiopoietin-like 3) inhibitor indicated as an adjunct to other low-density lipoprotein-cholesterol (LDL-C) lowering therapies for the treatment of adult and pediatric patients, aged 12 years and older, with homozygous familial hypercholesterolemia (HoFH). 

Limitations of Use:                                                                                                            • The safety and effectiveness of EVKEEZA have not been established in patients with other causes of hypercholesterolemia, including those with heterozygous familial hypercholesterolemia (HeFH). 

• The effects of EVKEEZA on cardiovascular morbidity and mortality have not been determined.

DOSAGE AND ADMINISTRATION

• The recommended dose of EVKEEZA is 15 mg/kg administered by intravenous (IV) infusion once monthly (every 4 weeks).

 • See the Full Prescribing Information for preparation instructions for the intravenous infusion.

 • 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.

 • 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. 

 ADVERSE REACTIONS

 Common adverse reactions (=5%) were nasopharyngitis, influenza-like illness, dizziness, rhinorrhea, and nausea. 

DOSAGE FORMS AND STRENGTHS-                                                                 Injection: 345 mg/2.3 mL (150 mg/mL) and 1,200 mg/8 mL (150 mg/mL) solution in single-dose vials.

 CONTRAINDICATIONS-

 • History of serious hypersensitivity reactions to evinacumab-dgnb or to any of the excipients in EVKEEZA.

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.

 • 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 dose.

(5.2, 8.1, 8.3) ___________________ ADVERSE REACTIONS ___________________ Common adverse reactions (=5%) were nasopharyngitis, influenza-like illness, dizziness, rhinorrhea, and nausea. (6.1)

DOSAGE AND ADMINISTRATION

• The recommended dose of EVKEEZA is 15 mg/kg administered by intravenous (IV) infusion once monthly (every 4 weeks)                                                                             .

• See the Full Prescribing Information for preparation instructions for the intravenous infusion.

 • 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.

 • 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. 

DOSAGE FORMS AND STRENGTHS-                                                                 Injection: 345 mg/2.3 mL (150 mg/mL) and 1,200 mg/8 mL (150 mg/mL) solution in single-dose vials.

 • The rate of infusion may be slowed, interrupted or discontinued if the patient develops any signs of adverse reactions, including infusion or hypersensitivity reactions. 

 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 

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 dose.

Encourage patients who become pregnant to report their pregnancy to 1-833-385-3392 

Manufactured by: Regeneron Pharmaceuticals, Inc. 777 Old Saw Mill River Road Tarrytown, NY 10591-6707 U.S. License No. 1760

EVKEEZA™ trademark is owned by Regeneron Pharmaceuticals Inc. All rights reserved. © 2021, Regeneron Pharmaceuticals, Inc.

 CLINICAL PHARMACOLOGY-

1. Mechanism 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).

2. Pharmacodynamics-                                                                                               Administration of evinacumab-dgnb in HoFH patients resulted in reductions in LDL-C, total cholesterol (TC), HDL-C, apolipoprotein B and TG 

3. Pharmacokinetics                                                                                                     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.

Distribution -                                                                                                                 The total volume of distribution estimated via population pharmacokinetic analysis was approximately 4.8 L.

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.

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 95 patients with HoFH suggests that the following factors have no clinically significant effect on the exposure of evinacumab-dgnb: age (12 to 75 years), gender, body weight (42 to 152 kg), and race (White, Asian, Black, and Other).

Pediatric Patients-                                                                                                            A 15-year-old patient 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.

Patients with Renal Impairment Observed trough serum evinacumab-dgnb concentrations at steady-state were comparable between patients with mild or moderate renal impairment and patients with normal renal function. No data are available in patients with severe renal impairment

 Patients with Hepatic Impairment No data are available in patients with hepatic impairment.

Drug Interaction Studies-                                                                                                Drug interaction studies have not been conducted with evinacumab-dgnb. In a clinical trial, the concentrations of statins (atorvastatin, rosuvastatin, simvastatin) were not meaningfully altered in  patients taking statins prior to and post administration of evinacumab-dgnb. Concentrations of evinacumab-dgnb were comparable in patients with HoFH taking or not taking background lipidlowering therapy.

 USE IN SPECIFIC POPULATIONS

1. Pregnancy 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 drugassociated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

The estimated background risk of major birth defects and miscarriage for the indicated population are unknown.

2 Lactation 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 production. Maternal IgG is known to be present in human milk.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for EVKEEZA and any potential adverse effects on the breastfed infant from EVKEEZA or from the underlying maternal condition.

3. Females and Males of Reproductive Potential-                                                Pregnancy Testing Consider pregnancy testing in patients who may become pregnant prior to starting treatment with EVKEEZA

Contraception-                                                                                                          Females Based on animal studies, EVKEEZA may cause fetal harm when administered to pregnant patients.

Patients who may become pregnant should use effective contraception during treatment with EVKEEZA and for at least 5 months following the last dose of EVKEEZA.

4. Pediatric 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 12 years and older.

Use of EVKEEZA for this indication is supported by evidence from adequate and well-controlled trials in adults with additional efficacy and safety data in pediatric patients aged 12 years and older.

The safety and effectiveness of EVKEEZA have not been established in pediatric patients with HoFH who are younger than 12 years old.

5. Geriatric 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.