Erenumab

Identification

Summary

Erenumab is a calcitonin-gene related peptide antagonist used to prevent migraines.

Brand Names

Aimovig

Generic Name

Erenumab

DrugBank Accession Number

DB14039

Background

Erenumab (AMG-334) (INN; trade name Aimovig) is a human monoclonal antibody designed specifically to bind and antagonize the calcitonin gene-related peptide receptor (CGRPR) as a means to prevent migraines. Aimovig, as released and marketed by Novartis and Amgen, is in fact a novel therapeutic approach as the first and only FDA approved treatment specifically developed to prevent migraine by blocking the CGRP receptor, which is believed to play a critical role in migraine ³.

In particular, erenumab-aooe is a human immunoglobulin G2 monoclonal antibody that has high affinity binding to the CGRP receptor ^Label. The antibody is produced utlilizing recombinant DNA technology in Chinese hamster ovary cells ^Label. It is composed of 2 heavy chains, each containing 456 amino acids, and 2 light chains of the lambda subclass, each containing 216 amino acids, with an approximate molecular weight of 150 kDa ^Label.

Type

Biotech

Groups

Approved, Investigational

Biologic Classification

Protein Based Therapies
Monoclonal antibody (mAb)

Protein Chemical Formula

C₆₄₇₂H₉₉₆₄N₁₇₂₈O₂₀₁₈S₅₀

Protein Average Weight

Not Available

Sequences

> Erenumab (Heavy chain)
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSFGMHWVRQAPGKGLEWVAVISFDGSIKYS
VDSVKGRFTISRDNSKNTLFLQMNSLRAEDTAVYYCARDRLNYYDSSGYYHYKYYGMAVW
GQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGV
HTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCP
APPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTL
PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLT
VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

> Erenumab (Light chain)
QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIP
DRFSGSKSGTSTTLGITGLQTGDEADYYCGTWDSRLSAVVFGGGTKLTVLGQPKANPTVT
LFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASS
YLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS

Download FASTA Format

Synonyms

Erenumab
erenumab-aooe

External IDs

AMG 334
AMG-334
AMG334

Pharmacology

Indication

Erenumab is indicated for the preventative treatment of migraine in adults ^Label.

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Associated Conditions

Migraine

Contraindications & Blackbox Warnings

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Pharmacodynamics

As a human monoclonal antibody designed to specifically bind with and antagonize the calcitonin gene-related peptide (CGRP) receptor, there is the possibility that erenumab could interfere with natural activities of CGRP that may not be immediately or directly associated with migraines. For example, at peripheral synapses, CGRP released from trigeminal terminals results in vasodilation by way of CGRP receptor on smooth muscle cells of meningeal and cerebral blood vessels, making CGRP a potent general arterial vasodilator ¹. Antagonism of CGRP receptors responsible for such vasodilation could theoretically result in vasoconstriction and raises in blood pressure.

In a randomised, double-blind, placebo-controlled study in healthy volunteers, concomitant administration of erenumab (140 mg intravenous, single dose) with sumatriptan (12 mg subcutaneous, given as two 6 mg doses separated by one hour) had no effect on resting blood pressure compared with sumatriptan alone, however ^Label. Please note that erenumab is indicated for subcutaneous use only, though ^Label.

Mechanism of action

Erenumab is a human monoclonal antibody that has been designed to bind specifically to the calcitonin gene-related peptide (CGRP) receptor and antagonize the CGRP receptor function ^Label.

Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy ¹. Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients ¹. For all these reasons, the binding and antagonism of CGRP receptors was designed to be mechanism of action for erenumab to take advantage of in reversing the migraine-inducing activity of natural CGRP.

CGRP and its receptor are expressed in both the peripheral and the central nervous system ². In addition to playing a role in cranial nociception, CGRP is also a potent general arterial vasodilator ². At peripheral synapses, CGRP released from trigeminal terminals results in vasodilation via CGRP receptors on the smooth muscle cells of meningeal and cerebral blood vessels ¹.

Target	Actions	Organism
UCalcitonin gene-related peptide type 1 receptor	Not Available	Humans

Absorption

Following a single subcutaneous dose of 70 mg or 140 mg erenumab administered to healthy adults, the median peak serum concentrations were attained in about 6 days, and the estimated absolute bioavailability was approximately 82% ^Label.

Volume of distribution

After a single 140 mg intravenous dose, the mean (SD) volume of distribution during the terminal phase (Vz) was estimated to be approximately 3.86 (0.77) L ^Label.

Protein binding

Readily accessible data regarding the protein binding of erenumab is not available, although it is reported that erenumab is capable of 50% to 99% total inhibition of calcitonin gene-related peptide receptors with dosages of 255 ng/mL and 1134 ng/mL, respectively ².

Metabolism

Erenumab CGRP antibodies demonstrate a low risk for drug-drug interactions and hepatotoxicity since they are predominantly metabolized by degradation into peptides and single amino acids ¹.

Route of elimination

Two elimination phases are observed for erenumab. At low concentrations, the elimination is mainly through saturable binding to target (CGRP receptor), while at higher concentrations the elimination of erenumab is primarily through a non-specific, non-saturable proteolytic pathway ^Label. These phases correspond to studies that demonstrated two parallel elimination pathways: (a) a slow non-specific elimination pathway through the hepatic reticuloendothelial system, and (b) a rapid saturable elimination pathway mediated by degradation or internalization of the erenumab-receptor complex ².

Half-life

Erenumab exhibits non-linear kinetics as a result of binding to the CGRP receptor ^Label. Lower than 2-fold accumulation was recorded in trough serum concentrations (Cmin) for episodic and chronic migraine patients following subcutaneous administration of 70 mg once-monthly and 140 mg once-monthly doses ^Label. Serum trough concentrations approached steady state by 3 months of dosing ^Label. The effective half-life of erenumab was observed to be 28 days ^Label.

Clearance

Certain studies show that the population estimate of linear clearance is independent of erenumab concentrations and stays approximately constant at 0.214 L/day (95% CI: 0.191–0.243) ². In contrast, the nonlinear clearance is dependent on the target receptor density and the amount of erenumab bound to the receptors ². Nevertheless, the maximal nonlinear clearance was observed to be about 1.84L/day ².

Adverse Effects

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Toxicity

The most common side effects of erenumab include pain, redness, or swelling at the injection site, and constipation. Information regarding overdosage is not available ^Label.

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.

Drug	Interaction
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Abciximab	The risk or severity of adverse effects can be increased when Abciximab is combined with Erenumab.
Adalimumab	The risk or severity of adverse effects can be increased when Adalimumab is combined with Erenumab.
Adenovirus type 7 vaccine live	The risk or severity of adverse effects can be increased when Erenumab is combined with Adenovirus type 7 vaccine live.
Aducanumab	The risk or severity of adverse effects can be increased when Aducanumab is combined with Erenumab.
Alemtuzumab	The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Erenumab.
Alirocumab	The risk or severity of adverse effects can be increased when Alirocumab is combined with Erenumab.
Amivantamab	The risk or severity of adverse effects can be increased when Erenumab is combined with Amivantamab.
Anifrolumab	The risk or severity of adverse effects can be increased when Anifrolumab is combined with Erenumab.
Ansuvimab	The risk or severity of adverse effects can be increased when Erenumab is combined with Ansuvimab.
Anthrax immune globulin human	The risk or severity of adverse effects can be increased when Erenumab is combined with Anthrax immune globulin human.

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Food Interactions

No interactions found.

Products

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Aimovig	Injection, solution	140 mg	Subcutaneous	Novartis Europharm Limited	2020-12-16	Not applicable
Aimovig	Injection, solution	70 mg	Subcutaneous	Novartis Europharm Limited	2020-12-16	Not applicable
Aimovig	Injection	70 mg/1mL	Subcutaneous	AMGEN INC	2018-05-22	Not applicable
Aimovig	Solution	140 mg / mL	Subcutaneous	Novartis	Not applicable	Not applicable
Aimovig	Solution	70 mg / mL	Subcutaneous	Novartis	2018-12-04	Not applicable
Aimovig	Injection, solution	140 mg	Subcutaneous	Novartis Europharm Limited	2020-12-16	Not applicable
Aimovig	Injection, solution	140 mg/1mL	Subcutaneous	AMGEN INC	2019-03-15	Not applicable
Aimovig	Injection, solution	70 mg	Subcutaneous	Novartis Europharm Limited	2020-12-16	Not applicable
Aimovig	Injection, solution	140 mg	Subcutaneous	Novartis Europharm Limited	2020-12-16	Not applicable
Aimovig	Injection, solution	140 mg/1mL	Subcutaneous	AMGEN INC	2019-03-15	Not applicable

Chemical Identifiers

UNII: I5I8VB78VT
CAS number: 1582205-90-0

References

General References

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. [Article]
Vu T, Ma P, Chen JS, de Hoon J, Van Hecken A, Yan L, Wu LS, Hamilton L, Vargas G: Pharmacokinetic-Pharmacodynamic Relationship of Erenumab (AMG 334) and Capsaicin-Induced Dermal Blood Flow in Healthy and Migraine Subjects. Pharm Res. 2017 Sep;34(9):1784-1795. doi: 10.1007/s11095-017-2183-6. Epub 2017 Jun 7. [Article]
Press Release: Novartis and Amgen announce FDA approval of Aimovig(TM) (erenumab), a novel treatment developed specifically for migraine prevention [Link]
FDA Approved Drug Products: AIMOVIG (erenumab-aooe) injection, for subcutaneous use [Link]

External Links

KEGG Drug: D10928
RxNav: 2045613
Wikipedia: Erenumab

FDA label

Download (1.57 MB)

MSDS

Download (35.7 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Completed	Health Services Research	Migraine	1
4	Completed	Prevention	Migraine	3
4	Completed	Supportive Care	Migraine	1
4	Completed	Treatment	Episodic Migraine	1
4	Completed	Treatment	Facial Pain / Rhino Sinusitis	1
4	Completed	Treatment	Migraine	5
4	Recruiting	Other	Headache / Migraine	1
4	Recruiting	Other	Migraine	1
4	Terminated	Prevention	Migraine	1
4	Terminated	Treatment	Migraine	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection	Subcutaneous
Injection	Subcutaneous	70 mg/1mL
Injection, solution	Subcutaneous	140 mg/1mL
Injection, solution	Subcutaneous	140 MG
Injection, solution	Subcutaneous	70 MG
Solution	Subcutaneous	140 mg / mL
Solution	Subcutaneous	70 mg / mL
Injection, solution	Subcutaneous	70 mg/1ml
Injection, solution	Subcutaneous	70 mg/ml
Injection, solution	Subcutaneous	140 MG/ML
Solution	Subcutaneous	70.000 mg
Solution	Subcutaneous	140 mg/ml
Solution	Subcutaneous	140 mg
Solution	Subcutaneous	70 mg

Prices

Not Available

Patents

Not Available

Properties

State: Liquid
Experimental Properties: Not Available

Targets

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Details1. Calcitonin gene-related peptide type 1 receptor

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Receptor for calcitonin-gene-related peptide (CGRP) together with RAMP1 and receptor for adrenomedullin together with RAMP3 (By similarity). Receptor for adrenomedullin together with RAMP2. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Specific Function: Adrenomedullin receptor activity
Gene Name: CALCRL
Uniprot ID: Q16602
Uniprot Name: Calcitonin gene-related peptide type 1 receptor
Molecular Weight: 52928.98 Da

Drug created at May 18, 2018 13:55 / Updated at June 03, 2022 07:24

Erenumab

Identification

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Targets