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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- Contraindications & Blackbox Warnings
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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
Target Actions Organism ACalcitonin gene-related peptide 1 antibodyHumans ACalcitonin gene-related peptide 2 antibodyHumans - 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 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Galcanezumab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Galcanezumab. Aducanumab The risk or severity of adverse effects can be increased when Aducanumab is combined with Galcanezumab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Galcanezumab. Alirocumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Galcanezumab. Amivantamab The risk or severity of adverse effects can be increased when Galcanezumab is combined with Amivantamab. Anifrolumab The risk or severity of adverse effects can be increased when Anifrolumab is combined with Galcanezumab. Ansuvimab The risk or severity of adverse effects can be increased when Galcanezumab is combined with Ansuvimab. Anthrax immune globulin human The risk or severity of adverse effects can be increased when Anthrax immune globulin human is combined with Galcanezumab. Antilymphocyte immunoglobulin (horse) The risk or severity of adverse effects can be increased when Antilymphocyte immunoglobulin (horse) is combined with Galcanezumab. 
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- Avoid alcohol.
- Take with or without food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Emgality Solution 100 mg / mL Subcutaneous Eli Lilly & Co. Ltd. 2021-01-11 Not applicable Canada 
Emgality Injection, solution 120 mg Subcutaneous Eli Lilly Nederland B.V. 2020-12-16 Not applicable EU 
Emgality Solution 120 mg / mL Subcutaneous Eli Lilly & Co. Ltd. 2019-10-07 Not applicable Canada Emgality Injection, solution 120 mg Subcutaneous Eli Lilly Nederland B.V. 2020-12-16 Not applicable EU Emgality Injection, solution 120 mg/1mL Subcutaneous Eli Lilly and Company 2018-09-27 Not applicable US 
Emgality Injection, solution 120 mg Subcutaneous Eli Lilly Nederland B.V. 2020-12-16 Not applicable EU Emgality Solution 120 mg / mL Subcutaneous Eli Lilly & Co. Ltd. 2019-10-02 Not applicable Canada Emgality Injection, solution 120 mg Subcutaneous Eli Lilly Nederland B.V. 2020-12-16 Not applicable EU Emgality Injection, solution 100 mg/1mL Subcutaneous Eli Lilly and Company 2019-06-04 Not applicable US Emgality Injection, solution 120 mg Subcutaneous Eli Lilly Nederland B.V. 2020-12-16 Not applicable EU
Categories
- ATC Codes
- N02CD02 — Galcanezumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Analgesics
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antimigraine Preparations
- Blood Proteins
- Calcitonin Gene-Related Peptide (CGRP) Antagonists
- Calcitonin Gene-Related Peptide Receptor Antagonists
- Central Nervous System Agents
- Globulins
- Immunoglobulins
- Immunoproteins
- Nervous System
- Peripheral Nervous System Agents
- Proteins
- Sensory System Agents
- Serum Globulins
- 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
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- FDA Approved Drug Products: EMGALITY (galcanezumab-gnlm) injection for subcutaneous use [Link]
- External Links
- 2058846
- Wikipedia
- Galcanezumab
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Episodic Migraine / Migraine 1 4 Completed Treatment Glossopharyngeal Neuralgia / Trigeminal Neuralgia (TN) 1 4 Completed Treatment Migraine 1 4 Enrolling by Invitation Treatment Migraine 1 4 Recruiting Basic Science Chronic Migraine 1 4 Terminated Treatment Migraine 1 3 Completed Treatment Chronic Cluster Headache 1 3 Completed Treatment Chronic Cluster Headache / Episodic Cluster Headache 1 3 Completed Treatment Chronic Migraine 1 3 Completed Treatment Episodic Cluster Headache 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Parenteral; Subcutaneous 120 MG Injection, solution Subcutaneous 100 mg/1mL Injection, solution Subcutaneous 120 mg/1mL Injection, solution Subcutaneous 120 mg Solution Subcutaneous 100 mg / mL Solution Subcutaneous 120 mg Solution Subcutaneous 120 mg / mL Injection, solution 120 mg/ml Injection, solution Subcutaneous 120 mg/ml Injection, solution Subcutaneous 100 mg/ml - 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
- 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
- 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