Galcanezumab

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Summary

Galcanezumab is a calcitonin-gene related peptide antagonist used to prevent migraines and treat cluster headaches.

Brand Names
Emgality
Generic Name
Galcanezumab
DrugBank Accession Number
DB14042
Background

Galcanezumab is a humanized monoclonal antibody developed by Eli Lilly and Company against human calcitonin gene-related peptide (CGRP).1 Although several small-molecule CGRP receptor antagonists have been developed, humanized monoclonal antibodies like galcanezumab are specifically designed to selectively bind to CGRP entities with high potency.3 Given this target specificity, lack of off-target toxicity, and characteristic proteolysis profile of immunoglobulin antibodies to not undergo metabolism by liver enzymes, galcanezumab possesses favourable and promising safety and tolerability.3 Galcanezumab was approved by the FDA in September 2018, and is indicated for the preventive treatment of migraine and the treatment of episodic cluster headache.8 It is unknown if galcanezumab has an effect on pregnancy outcomes. A pregnancy exposure registry has been established to evaluate the safety of this drug in pregnant women.8

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
Not Available
Protein Average Weight
147000.0 Da (Approximate)
Sequences
>galcanezumab|Heavy
QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVY
IQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSSA
STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
LYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVF
LFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR
VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN
QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN
VFSCSVMHEALHNHYTQKSLSLSLG
>galcanezumab|Light
DIQMTQSPSSLSASVGDRVTITCRASKDISKYLNWYQQKPGKAPKLLIYYTSGYHSGVPS
RFSGSGSGTDFTLTISSLQPEDFATYYCQQGDALPPTFGGGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
Synonyms
  • Galcanezumab
  • Galcanezumab-gnlm
External IDs
  • LY-2951742
  • LY2951742

Pharmacology

Indication

Galcanezumab is indicated in adults for the preventive treatment of migraine and the treatment of episodic cluster headache.8

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofEpisodic cluster headache••••••••••••••••••••••••••
Prophylaxis ofMigraine headache••••••••••••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Galcanezumab is administered as a subcutaneous injection.3,5,8 During clinical trials, it was noted that galcanezumab therapy significantly reduced the mean number of migraine headache days and a good tolerability profile.1 Additionally, post hoc efficacy analyses showed that 32% of patients given galcanezumab responded to treatment, compared to 18% in the placebo group.1. Hypersensitivity reactions, including dyspnea, urticaria, and rash, have been reported in patients using galcanezumab. Cases of anaphylaxis and angioedema have also been reported in the postmarketing setting.8

Mechanism of action

Galcanezumab is a humanized monoclonal antibody that targets and binds calcitonin gene-related peptide (CGRP).8 Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy.6 Also, research has shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients.6 For these reasons, binding to CGRP to interfere with its activity was specifically designed as the mechanism of action for galcanezumab, in order to reverse the migraine-inducing activity of natural CGRP. By binding to natural endogenous CGRP, galcanezumab interferes with its activities by making it unable to bind to CGRP receptors.8 Moreover, studies have shown that humanized monoclonal antibodies against CGRP have successfully reduced the frequency of migraine headaches in early clinical trials as a preventative therapeutic.3

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

Galcanezumab follows a linear pharmacokinetic profile, with a Cmax and AUC0-∞ considered to be dose-proportional between 1 and 600 mg.3,8 After a single dose of galcanezumab-gnlm administered subcutaneously, the time to maximum concentration was 5 days.8 In a group of healthy subjects (n=7) given four biweekly doses of galcanezumab, Tmax was 3 days, Cmax was 37,210 ng/mL and the AUC was 1,959,000 ng⋅day/mL.3 The injection site location does not appear to significantly influence the absorption of this drug.8 Galcanezumab is expected to have a subcutaneous bioavailability between 50% and 100%, similar to other monoclonal antibodies.7

Renal and hepatic impairment are not expected to have an effect on the pharmacokinetics of galcanezumab. A population analysis has shown that pharmacokinetic parameters are not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), while body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab.8

Volume of distribution

The apparent volume of distribution of galcanezumab is 7.3 L, with 34% inter-individual variability.8

Protein binding

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

Metabolism

After administration, galcanezumab is expected to be degraded into small peptides and amino acids by proteolysis, in a process similar to the one followed by endogenous immunoglobulins.8 Galcanezumab is not believed to be metabolized by liver enzymes, making drug-drug interactions relatively unlikely.8

Route of elimination

Monoclonal antibody agents like galcanezumab are generally eliminated via intracellular catabolism, followed by fluid-phase or receptor-mediated endocytosis.7

Half-life

Between 1 and 600 mg of galcanezumab, the mean serum half-life ranged from 25 to 30 days.3 On average, the elimination half-life of galcanezumab was approximately 27 days.8

Clearance

The apparent clearance of galcanezumab is 0.008 L/h.8

Adverse Effects
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Toxicity

Toxicity information regarding galcanezumab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as nasopharyngitis, hematuria, and contact dermatitis.3 Symptomatic and supportive measures are recommended. Additional adverse effects reported in healthy subjects receiving a single high dose of galcanezumab (600 mg) were diarrhea, vomiting and high levels of alanine aminotransferase.3

Studies evaluating the carcinogenic potential or genetic toxicology of galcanezumab have not yet been conducted.8 No adverse effects were observed in male rats given galcanezumab (0, 30, or 250 mg/kg) subcutaneously before or during mating. The highest dose given to male rats corresponded to 8 or 4 times the recommended human dose for migraine (120 mg) or episodic cluster headache (300 mg), respectively.8 Female rats given 0, 30, 100 or 250 mg/kg of galcanezumab did not show adverse effects on fertility either. The highest dose given to female rats corresponded to 38 or 18 times the recommended human dose for migraine (120 mg) or episodic cluster headache (300 mg), respectively.8

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 Galcanezumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Galcanezumab.
AducanumabThe risk or severity of adverse effects can be increased when Aducanumab is combined with Galcanezumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Galcanezumab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Galcanezumab.
Food Interactions
  • Avoid alcohol.
  • Take with or without food.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
EmgalitySolution120 mg / mLSubcutaneousEli Lilly & Co. Ltd.2019-10-07Not applicableCanada flag
EmgalityInjection, solution120 mgSubcutaneousEli Lilly Nederland B.V.2020-12-16Not applicableEU flag
EmgalityInjection, solution120 mg/1mLSubcutaneousEli Lilly and Company2018-09-27Not applicableUS flag
EmgalitySolution100 mg / mLSubcutaneousEli Lilly & Co. Ltd.2021-01-11Not applicableCanada flag
EmgalityInjection, solution120 mgSubcutaneousEli Lilly Nederland B.V.2020-12-16Not applicableEU flag

Categories

ATC Codes
N02CD02 — Galcanezumab
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
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
55KHL3P693
CAS number
1578199-75-3

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. [Article]
  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. [Article]
  3. Monteith D, Collins EC, Vandermeulen C, Van Hecken A, Raddad E, Scherer JC, Grayzel D, Schuetz TJ, de Hoon J: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the CGRP Binding Monoclonal Antibody LY2951742 (Galcanezumab) in Healthy Volunteers. Front Pharmacol. 2017 Oct 17;8:740. doi: 10.3389/fphar.2017.00740. eCollection 2017. [Article]
  4. 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. [Article]
  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. [Article]
  6. 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]
  7. Kielbasa W, Helton DL: A new era for migraine: Pharmacokinetic and pharmacodynamic insights into monoclonal antibodies with a focus on galcanezumab, an anti-CGRP antibody. Cephalalgia. 2019 Sep;39(10):1284-1297. doi: 10.1177/0333102419840780. Epub 2019 Mar 27. [Article]
  8. FDA Approved Drug Products: EMGALITY (galcanezumab-gnlm) injection for subcutaneous use [Link]
RxNav
2058846
Wikipedia
Galcanezumab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingBasic ScienceChronic Migraine1
4CompletedTreatmentEpisodic Migraine / Migraine1
4CompletedTreatmentGlossopharyngeal Neuralgia / Trigeminal Neuralgia (TN)1
4CompletedTreatmentMigraine1
4TerminatedTreatmentMigraine2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionParenteral; Subcutaneous120 MG
Injection, solutionSubcutaneous100 mg/1mL
Injection, solutionSubcutaneous120 mg
Injection, solutionSubcutaneous120 mg/1mL
SolutionSubcutaneous100 mg / mL
SolutionSubcutaneous120 mg / mL
SolutionSubcutaneous120 mg
Injection, solution100 mg/ml
Injection, solution120 mg/ml
Injection, solutionSubcutaneous120 mg/ml
Injection, solutionSubcutaneous100 mg/ml
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

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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. Monteith D, Collins EC, Vandermeulen C, Van Hecken A, Raddad E, Scherer JC, Grayzel D, Schuetz TJ, de Hoon J: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the CGRP Binding Monoclonal Antibody LY2951742 (Galcanezumab) in Healthy Volunteers. Front Pharmacol. 2017 Oct 17;8:740. doi: 10.3389/fphar.2017.00740. eCollection 2017. [Article]
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. Monteith D, Collins EC, Vandermeulen C, Van Hecken A, Raddad E, Scherer JC, Grayzel D, Schuetz TJ, de Hoon J: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the CGRP Binding Monoclonal Antibody LY2951742 (Galcanezumab) in Healthy Volunteers. Front Pharmacol. 2017 Oct 17;8:740. doi: 10.3389/fphar.2017.00740. eCollection 2017. [Article]

Drug created at May 18, 2018 14:05 / Updated at July 02, 2022 12:49