Eptinezumab

Identification

Name
Eptinezumab
Accession Number
DB14040
Description

Eptinezumab is a fully-humanized IgG1 antibody manufactured using yeast (Pichia pastoris) and developed by Lundbeck Seattle Biopharmaceuticals.7 Eptinezumab has been specifically designed to bind to both alpha and beta forms of the human calcitonin gene-related peptide (CGRP).8,1,2,3 It was approved by the FDA in February 2020 for the preventive treatment of migraine headaches in adults.7

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
Not Available
Protein Average Weight
143000.0 Da
Sequences
>eptinezumab|Heavy
EVQLVESGGGLVQPGGSLRLSCAVSGIDLSGYYMNWVRQAPGKGLEWVGVIGINGATYYA
SWAKGRFTISRDNSKTTVYLQMNSLRAEDTAVYFCARGDIWGQGTLVTVSSASTKGPSVF
PLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVV
TVPSSSLGTQTYICNVNHKPSNTKVDARVEPKSCDKTHTCPPCPAPELLGGPSVTLFPPK
PKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVL
TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT
CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS
VMHEALHNHYTQKSLSLSPGK
>eptinezumab|Light
QVLTQSPSSLSASVGDRVTINCQASQSVYHNTYLAWYQQKPGKVPKQLIYDASTLASGVP
SRFSGSGSGTDFTLTISSLQPEDVATYYCLGSYDCTNGDCFVFGGGTKVEIKRTVAAPSV
FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
Synonyms
Not Available

Pharmacology

Indication

Eptinezumab is indicated for the preventive treatment of migraine in adults.7

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Eptinezumab is experimentally administered as an intravenous infusion and/or subcutaneous injection 1,3. During Phase 3 clinical trials, it was noted that patients with episodic migraine who on average had 8.6 days of migraine per month demonstrated significant reductions in migraine frequency over weeks 1-12, associated with the 300mg dose arm.6 Additionally, 29.7% of patients achieved a 75% or greater reduction in migraine days from baseline, compared to 16.2% for placebo (p<0.0007).6 Moreover, a post hoc analysis revealed that those patients achieving a 75% or greater response rate had over an eight-fold increase in days between migraines.6

Mechanism of action

Eptinezumab is a fully-humanized IgG1 antibody manufactured and designed specifically to bind both alpha and beta forms of the human calcitonin gene-related peptide (CGRP).8,1,2,3,5

Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy.4 Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients.4 For all these reasons, the binding of CGRP to interfere with its activity was specifically designed to be the form and mechanism of action for eptinezumab. The binding of eptinezumab to natural endogenous CGRP subsequently interferes with its activities, such as its binding to CGRP receptors, for example.

TargetActionsOrganism
ACalcitonin gene-related peptide 1
antibody
Humans
ACalcitonin gene-related peptide 2
antibody
Humans
Absorption

Eptinezumab is the only potent and selective and anti-calcitonin gene-related peptide (CGRP) monoclonal antibody administered by quarterly infusion for migraine prevention delivering 100% bioavailability by way of the intravenous route of administration to immediately inhibit CGRP .6

With an intravenous dose of eptinezumab 1000 mg, the mean maximum concentration of 336.4 ug/mL (SD 79.9) occurred after 4.8 hours after the start of the 1 hour infusion 3. The mean exposure to free eptinezumab, as characterized by area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration and from time zero to infinity were 8245 days per ug per mL (SD 2619) and 8722 days per ug per mL (SD 2522), respectively 3.

Volume of distribution

The central volume of distribution for eptinezumab is approximately 3.7 L.7

Protein binding

Readily accessible data regarding the protein binding of eptinezumab is not available.

Metabolism

Monoclonal antibody agents like eptinezumab are not expected to generate toxic metabolites as they generally undergo proteolysis to their constituent amino acids.8

Route of elimination

Monoclonal antibody agents like eptinezumab are generally not eliminated via hepatic, renal, or biliary routes.8

Half-life

The plasma half-life after an intravenous infusion is approximately 27 days.7

Clearance

The apparent clearance of eptinezumab is 0.006 L/h.7

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

The most frequent adverse events associated with eptinezumab use include upper respiratory tract infection, urinary tract infection, fatigue, back pain, arthralgia, and nausea and vomiting 3. No data regarding overdosage has been reported yet.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Eptinezumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Eptinezumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Eptinezumab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Eptinezumab.
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Anthrax immune globulin human is combined with Eptinezumab.
Antilymphocyte immunoglobulin (horse)The risk or severity of adverse effects can be increased when Antilymphocyte immunoglobulin (horse) is combined with Eptinezumab.
Antithymocyte immunoglobulin (rabbit)The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Eptinezumab.
Asfotase alfaThe risk or severity of adverse effects can be increased when Asfotase alfa is combined with Eptinezumab.
AtezolizumabThe risk or severity of adverse effects can be increased when Atezolizumab is combined with Eptinezumab.
AvelumabThe risk or severity of adverse effects can be increased when Avelumab is combined with Eptinezumab.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
No interactions found.

Products

Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
VyeptiInjection100 mg/1mLIntravenousLundbeck Pharmaceuticals Llc2020-02-21Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Chemical Identifiers

UNII
8202AY8I7H
CAS number
1644539-04-7

References

General References
  1. Pellesi L, Guerzoni S, Pini LA: Spotlight on Anti-CGRP Monoclonal Antibodies in Migraine: The Clinical Evidence to Date. Clin Pharmacol Drug Dev. 2017 Nov;6(6):534-547. doi: 10.1002/cpdd.345. Epub 2017 Apr 14. [PubMed:28409893]
  2. Benemei S, Cortese F, Labastida-Ramirez A, Marchese F, Pellesi L, Romoli M, Vollesen AL, Lampl C, Ashina M: Triptans and CGRP blockade - impact on the cranial vasculature. J Headache Pain. 2017 Oct 10;18(1):103. doi: 10.1186/s10194-017-0811-5. [PubMed:29019093]
  3. Dodick DW, Goadsby PJ, Silberstein SD, Lipton RB, Olesen J, Ashina M, Wilks K, Kudrow D, Kroll R, Kohrman B, Bargar R, Hirman J, Smith J: Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: a randomised, double-blind, placebo-controlled, exploratory phase 2 trial. Lancet Neurol. 2014 Nov;13(11):1100-1107. doi: 10.1016/S1474-4422(14)70209-1. Epub 2014 Oct 5. [PubMed:25297013]
  4. Deen M, Correnti E, Kamm K, Kelderman T, Papetti L, Rubio-Beltran E, Vigneri S, Edvinsson L, Maassen Van Den Brink A: Blocking CGRP in migraine patients - a review of pros and cons. J Headache Pain. 2017 Sep 25;18(1):96. doi: 10.1186/s10194-017-0807-1. [PubMed:28948500]
  5. Vollbracht S, Rapoport AM: New treatments for headache. Neurol Sci. 2014 May;35 Suppl 1:89-97. doi: 10.1007/s10072-014-1747-z. [PubMed:24867844]
  6. EconoTimes Business Article: Alder BioPharmaceuticals® New Data Demonstrated Eptinezumab Increased Migraine-Free Intervals (Up to 32.5 days) and Improved Quality-of-Life Outcomes in Patients with Episodic Migraine [Link]
  7. FDA Approved Drug Products: Vyepti (eptinezumab-jjmr) for intravenous injection [Link]
  8. Presentation on CGRP, MONOCLONAL ANTIBODIES AND SMALL MOLECULES (-GEPANTS) [File]
RxNav
2282660
Wikipedia
Eptinezumab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedPreventionMigraine Disorders3
3CompletedTreatmentMigraine1
3RecruitingTreatmentMigraine1
2CompletedPreventionMigraine Disorders1
1CompletedTreatmentHealthy Volunteers1
1RecruitingTreatmentMigraine / Migraine in Children1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionIntravenous100 mg/1mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antibody
General Function
Receptor binding
Specific Function
CGRP induces vasodilation. It dilates a variety of vessels including the coronary, cerebral and systemic vasculature. Its abundance in the CNS also points toward a neurotransmitter or neuromodulato...
Gene Name
CALCA
Uniprot ID
P06881
Uniprot Name
Calcitonin gene-related peptide 1
Molecular Weight
13897.755 Da
References
  1. Dodick DW, Goadsby PJ, Silberstein SD, Lipton RB, Olesen J, Ashina M, Wilks K, Kudrow D, Kroll R, Kohrman B, Bargar R, Hirman J, Smith J: Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: a randomised, double-blind, placebo-controlled, exploratory phase 2 trial. Lancet Neurol. 2014 Nov;13(11):1100-1107. doi: 10.1016/S1474-4422(14)70209-1. Epub 2014 Oct 5. [PubMed:25297013]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antibody
General Function
Neuropeptide hormone activity
Specific Function
CGRP induces vasodilation. It dilates a variety of vessels including the coronary, cerebral and systemic vasculature. Its abundance in the CNS also points toward a neurotransmitter or neuromodulato...
Gene Name
CALCB
Uniprot ID
P10092
Uniprot Name
Calcitonin gene-related peptide 2
Molecular Weight
13705.56 Da
References
  1. Dodick DW, Goadsby PJ, Silberstein SD, Lipton RB, Olesen J, Ashina M, Wilks K, Kudrow D, Kroll R, Kohrman B, Bargar R, Hirman J, Smith J: Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: a randomised, double-blind, placebo-controlled, exploratory phase 2 trial. Lancet Neurol. 2014 Nov;13(11):1100-1107. doi: 10.1016/S1474-4422(14)70209-1. Epub 2014 Oct 5. [PubMed:25297013]

Drug created on May 18, 2018 08:03 / Updated on August 01, 2020 06:25

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