AHFS Class:

• Calcitonin Gene-related Peptide (CGRP) Antagonists 28:32.12

Generic Name(s):

• Galcanezumab-gnlm

• Galcanezumab

Galcanezumab-gnlm, a recombinant humanized immunoglobulin G₄ (IgG₄) monoclonal antibody specific for calcitonin gene-related peptide (CGRP) ligand, is an antimigraine agent.1,9

Preventive Treatment of Migraine

Galcanezumab-gnlm is used for the preventive treatment of migraine.1,2,3,4,7 In clinical studies, galcanezumab prophylaxis substantially reduced monthly migraine days in patients with episodic or chronic migraine and reduced acute antimigraine agent-use days in patients with episodic migraine when compared with placebo.1,2,3,4

Clinical Experience

Efficacy and safety of galcanezumab for the preventive treatment of migraine have been established in 3 randomized, double-blind, placebo-controlled, multicenter studies in adults with a history of migraine, with or without aura, according to the International Classification of Headache Disorders, third edition, beta version (ICHD-3 beta) diagnostic criteria.1,2,3,4 Two studies of 6 months' duration included adults with episodic migraine (4-14 migraine days per month) and another study of 3 months' duration included adults with chronic migraine (at least 15 headache days per month with at least 8 migraine days per month).1,2,3,4 In all 3 studies, patients received treatment with galcanezumab-gnlm 120 mg (with an initial 240-mg loading dose), galcanezumab-gnlm 240 mg, or placebo given subcutaneously every month, and were permitted to use acute headache treatments, including antimigraine agents (e.g., selective serotonin type 1 [5-hydroxytryptamine type 1; 5-HT₁] receptor agonists [triptans], ergot alkaloids), nonsteroidal anti-inflammatory agents (NSAIAs), and acetaminophen, as needed during the studies.1,2,3,4 The studies excluded patients who failed to respond to adequate trials of 3 or more migraine preventive treatments, patients with ECG abnormalities indicating risk for acute cardiovascular events, and those with a recent history (within 6 months) of cardiovascular or cerebrovascular events (i.e., stroke, myocardial infarction [MI], unstable angina, percutaneous coronary intervention, coronary artery bypass grafting, deep-vein thrombosis [DVT], pulmonary embolism).1,2,3,4 The episodic migraine studies (EVOLVE-1 and -2) also excluded patients with medication overuse headache.1 Patients in EVOLVE-1 and -2 were not permitted to receive other preventive migraine treatments concurrently or within 30 days of the study baseline period,1,2,3 while concomitant use of stable dosages of either propranolol or topiramate as preventive antimigraine therapy was permitted in the chronic migraine study (REGAIN).1,4

The primary measure of efficacy in these studies was the mean change from baseline in monthly migraine days over the 6-month treatment period.1,2,3,4 Secondary end points included response rates (i.e., the proportion of patients achieving at least 50, 75, and 100% reductions in mean migraine days per month) and the mean change from baseline in the number of migraine days per month on which any acute headache medication was taken.1,2,3,4 A patient-reported outcome, the Migraine-Specific Quality of Life Questionnaire (MSQ) Role Function-Restrictive domain score that indicates the impact of migraine on daily activities, also was assessed.1,2,3,4 Higher MSQ scores (scaled from 0 to 100) indicate less impact of migraine on daily activities.1,2,4

In the episodic migraine studies (EVOLVE-1 and -2), a total of 1773 adults with episodic migraine underwent randomization and 1448 (82%) of the adults completed the 6-month, double-blind treatment phase.1 In the EVOLVE-1 and EVOLVE-2 study, monthly migraine days were reduced by 4.7 and 4.3 days, respectively, in patients who received galcanezumab 120 mg once monthly compared with a reduction of 2.8 and 2.3 days, respectively, in patients receiving placebo.1,2,3 Reductions in monthly migraine days were observed within the first month of galcanezumab treatment and were sustained throughout 6 months of treatment.1,2,3 Substantially greater proportions of patients receiving galcanezumab-gnlm 120 mg once monthly achieved at least 50, 75, or 100% reductions in mean migraine days per month compared with those receiving placebo.1,2,3 the mean number of migraine days per month that acute headache medication was taken was reduced by 4 and 3.7 days in EVOLVE-1 and -2, respectively, in patients receiving galcanezumab compared with 2.2 and 1.9 days, respectively, in placebo recipients.1,2,3 In addition, the MSQ Role Function-Restrictive domain scores were substantially improved in patients treated with galcanezumab-gnlm 120 mg once monthly compared with placebo.1,2,3 The 240-mg monthly dosage of galcanezumab-gnlm did not demonstrate additional clinical benefit compared with the 120-mg monthly dosage in these studies.1,2,3

In the chronic migraine study (REGAIN), 1113 adults with chronic migraine underwent randomization and 1037 (93%) of the adults completed the 3-month, double-blind treatment phase.1,4 From a mean baseline migraine frequency of approximately 19 migraine days per month, treatment with galcanezumab-gnlm 120 mg once monthly reduced monthly migraine days by 4.8 compared with a reduction of 2.7 days in patients receiving placebo.1,4 Reductions in monthly migraine days were evident in the first month of treatment with galcanezumab and were sustained through 3 months of treatment.1,4 At least a 50% reduction in mean migraine days per month was achieved in a substantially greater proportion of patients receiving galcanezumab-gnlm 120 mg compared with placebo (28 versus 15%, respectively).1,4 Treatment with the 240-mg monthly dosage did not demonstrate additional benefit over the 120-mg monthly dosage.1,4

Galcanezumab also was evaluated in a long-term, open-label, multicenter safety study in adults with migraine.7 A total of 270 patients with episodic or chronic migraine were enrolled (135 patients each received galcanezumab-gnlm 120 mg [with initial 240-mg loading dose] or 240 mg monthly by subcutaneous injection) and approximately 78% of those patients completed the 12-month treatment phase in the study.7 Although the primary objective of this study was to assess the long-term safety and tolerability of the drug, galcanezumab therapy was associated with reductions in monthly migraine days and acute antimigraine or headache agent-use days.7 Efficacy was observed as early as the first month of treatment and was sustained throughout the 12-month treatment period.7 This study demonstrated no substantial differences in efficacy between the 120- and 240-mg monthly dosages of the drug.7

Clinical Perspective

The American Headache Society (AHS) has published expert consensus statements on integrating new migraine treatments into clinical practice over the last years.12,23 AHS states that galcanezumab and other anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies offer a number of advantages over some oral migraine preventive therapies, including no need for dosage escalation, rapid onset of therapeutic activity (within days to weeks), demonstrated efficacy after failure of prior preventive treatments or in combination with oral preventive treatments, minimal risk of adverse drug interactions, and favorable overall tolerability profiles.12,23 In 2024, AHS stated that CGRP-targeting therapies should be considered as a first-line approach for migraine prevention along with previous first-line treatments, without a requirement for prior failure of other migraine preventive drug classes.24 AHS noted that the cumulative evidence for the efficacy, safety, and tolerability of CGRP-targeting therapies is significantly greater than that for any established migraine preventive therapy.24

Similar to other commercially available antimigraine agents, galcanezumab is unlikely to achieve complete migraine freedom, but substantial reductions in migraine frequency were observed in controlled clinical trials.1,2,3,4,5

Treatment of Episodic Cluster Headache

Galcanezumab-gnlm is used for the treatment of episodic cluster headache.1,22 In the principal efficacy study, galcanezumab treatment substantially reduced weekly cluster headache attack frequency in patients with episodic cluster headache compared with placebo.1,22

Cluster headache is a type of headache that produces extreme pain and is highly debilitating.15,16,17 The headaches usually occur in clusters, often at the same time of day (commonly in the overnight hours), and last for several weeks or months (i.e., cluster periods or bouts) separated by remission periods lasting months or years in patients with episodic cluster headache.15,16,17 In patients with chronic cluster headache, attacks occur for one year or longer without remission or with remission periods lasting less than 3 months.17 Cluster headache attacks are characterized by unilateral pain, which may be orbital, supraorbital, temporal, or in any combination of these areas; attacks usually last between 15 minutes and 3 hours and occur from once every day to up to 8 times daily.15,16,17 Cluster headache pain may be accompanied by a variety of clinical manifestations, which may include ipsilateral conjunctival injection or lacrimation, rhinorrhea and/or nasal congestion, miosis, ptosis and/or eyelid edema, forehead and facial sweating, and/or restlessness or agitation.15,16,17 Age of onset of cluster headache is usually 20-40 years, and the condition is 3 times more common in men than women.17 Diagnosis of cluster headache is often delayed in the US, and the incidence of suicidality in affected patients is substantial (occurring in 55% of patients).16

Efficacy of galcanezumab for the treatment of episodic cluster headache has been established in a randomized, double-blind, placebo-controlled study of 8 weeks' duration in adults with episodic cluster headache according to the ICHD-3 beta diagnostic criteria.1,22 Patients enrolled in the study had a maximum of 8 cluster headache attacks each day, a minimum of 1 attack every other day, and at least 4 attacks during the prospective 7-day baseline period.1,22 Patients were randomized to receive either once-monthly subcutaneous injections of galcanezumab-gnlm 300 mg or placebo, and were permitted to use certain acute/abortive cluster headache treatments during the study, including triptans, acetaminophen, NSAIAs, and oxygen.1,22 Patients receiving other treatments intended to reduce the frequency of cluster headache attacks, patients with medication overuse headache, and patients with ECG abnormalities consistent with an acute cardiovascular event or conduction delay or a recent history (within 6 months) of cardiovascular or cerebrovascular events (i.e., MI, unstable angina, percutaneous coronary intervention, coronary artery bypass grafting, DVT, pulmonary embolism) were excluded from the study.1,22 Patients with a history of stroke, intracranial or carotid aneurysm, intracranial hemorrhage, or vasospastic angina; clinical evidence of peripheral vascular disease; or Raynaud's disease also were excluded.1,22

The primary efficacy end point in the study was the mean change from baseline in weekly cluster headache attack frequency from weeks 1 to 3, and a secondary end point was the proportion of patients who achieved a response (defined as a reduction from baseline of at least 50% in weekly cluster headache attack frequency) at week 3.1,22 Out of 106 patients who were randomized and treated, 90 patients completed the 8-week, double-blind phase of the study.1,22 During the 3-week period, patients taking galcanezumab experienced 8.7 fewer weekly cluster headache attacks than they did at baseline, compared with 5.2 fewer attacks for patients receiving placebo; 71.4% of patients taking galcanezumab were responders at week 3 compared with 52.6% of those receiving placebo.1,22 Although study enrollment was stopped before reaching the planned sample size due to the low number of patients entering an active cluster bout during the screening period, available data were sufficient for analysis of the primary and secondary end points.22 Larger and longer-term studies are needed to better determine the durability of response and safety profile of galcanezumab in patients with episodic cluster headache.22

General

Patient Monitoring

• Monitor for hypersensitivity reactions, including anaphylaxis.1

Administration

Galcanezumab-gnlm is administered by subcutaneous injection only.1 Galcanezumab-gnlm injection is commercially available in single-dose prefilled auto-injectors (i.e., injection pens), which contain 120 mg of the drug, and single-dose prefilled syringes, which contain either 100 or 120 mg of the drug.1 Both formulations of the drug are intended for patient self-administration .1

Prior to use, patients and/or caregivers should receive proper training on how to prepare and administer galcanezumab-gnlm using the single-dose prefilled auto-injectors or syringes, including aseptic technique.1 The manufacturer's labeling should be consulted for detailed instructions regarding subcutaneous administration of the drug.1

Galcanezumab-gnlm should be administered subcutaneously into the abdomen, anterior thigh, back of the upper arm, or buttocks; injections within 2 inches of the navel, knee, or groin should be avoided.1 The back of the upper arm or buttocks may be used if someone other than the patient is administering the injection (e.g., caregiver, healthcare professional).1 Multiple injections of the drug (i.e., the initial loading dose for preventive treatment of migraine consisting of 2 injections and the dose for treatment of episodic cluster headache consisting of 3 injections) may be administered at separate locations at the same body site.1 Injection into areas where the skin is tender, bruised, erythematous, or indurated should be avoided.1

Prefilled auto-injectors and syringes of galcanezumab-gnlm should be stored at 2-8°C in the original carton to protect from light until time of use.1 These formulations of the drug may be stored at room temperature up to 30°C in the original carton for up to 7 days; they should not be returned to the refrigerator after storage at room temperature for longer than 1 hour.1,14 The prefilled auto-injectors and syringes should not be frozen or shaken.1 If the auto-injectors or syringes are stored at room temperature for more than 7 days or are frozen or shaken vigorously (i.e., shaking beyond the normal vibration, shaking, or bumping that occurs during typical transport activities), they should be discarded.1,14 If galcanezumab-gnlm prefilled auto-injectors or syringes are exposed to conditions outside of the recommended storage and handling conditions, the manufacturer may be able to provide further information regarding stability and product quality assessment; patients or healthcare professionals may contact the manufacturer by calling 800-545-5979.14

Prior to subcutaneous administration, prefilled auto-injectors and syringes of galcanezumab-gnlm should be removed from their carton and allowed to sit at room temperature for 30 minutes; exposure to direct sunlight should be avoided.1 The auto-injectors and syringes should not be warmed by using a heat source (e.g., microwave, hot water).1 Prior to administration, the solution should be inspected visually for particulate matter and discoloration; the prefilled auto-injector or syringe should not be used if the solution is cloudy or discolored or contains particles.1 The prefilled auto-injectors and syringes are intended for single use only and should be discarded after use.1

Dosage

Preventive Treatment of Migraine

For the preventive treatment of migraine in adults, therapy with galcanezumab-gnlm should be initiated with a one-time loading dose of 240 mg (administered as 2 consecutive subcutaneous injections of 120 mg each) followed by monthly doses of 120 mg by subcutaneous injection.1 In clinical studies, a higher dosage of galcanezumab-gnlm (240 mg once monthly) did not demonstrate additional clinical benefit over the recommended dosage (120 mg once monthly).1,2,3,4,7 The American Headache Society (AHS) recommends assessing the clinical efficacy of galcanezumab after 3 months of treatment and continuing therapy only if treatment benefits have been observed with the drug by that time.12,23

If a dose of galcanezumab is missed, the missed dose should be administered as soon as possible.1 Subsequent doses may then be scheduled monthly from the date of the last administered dose.1

The risk of adverse drug interactions with galcanezumab appears to be minimal.1,12 When initiating therapy with galcanezumab or another anti-calcitonin gene-related peptide (CGRP) monoclonal antibody in a patient who is already receiving a preventive treatment for migraine, AHS recommends adding the anti-CGRP monoclonal antibody to the existing antimigraine regimen.12 The decision to discontinue the established preventative therapy should take into account the onset and magnitude of treatment effect with the anti-CGRP monoclonal antibody.23

Treatment of Episodic Cluster Headache

For the treatment of episodic cluster headache in adults, the recommended dosage of galcanezumab-gnlm is 300 mg (administered as 3 consecutive subcutaneous injections of 100 mg each) at the onset of the cluster period and then monthly until the end of the cluster period.1

If a dose of galcanezumab is missed, the missed dose should be administered as soon as possible.1 Subsequent doses may then be scheduled monthly from the date of the last administered dose until the end of the cluster period.1

Special Populations

Hepatic Impairment

The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.1

Renal Impairment

The manufacturer makes no specific dosage recommendations for patients with renal impairment.1

Geriatric Patients

Insufficient data in adults >65 years of age to make specific dosage recommendations.1

Contraindications

• Galcanezumab is contraindicated in patients with serious hypersensitivity to the drug or to any of the excipients in the formulation.1

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, angioedema, rash, urticaria, and dyspnea, have been reported in patients receiving galcanezumab.1 Hypersensitivity reactions may occur days after administration of galcanezumab and may be prolonged.1

If a serious or severe hypersensitivity reaction occurs during galcanezumab therapy, the drug should be discontinued and appropriate medical therapy initiated.1

The manufacturer states that the prefilled auto-injectors and syringes of galcanezumab-gnlm are not made with natural rubber latex.1

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity with galcanezumab therapy.1 In controlled clinical studies of up to 6 months' duration, anti-galcanezumab antibodies were detected in 33 of 688 patients (4.8%) who received galcanezumab once monthly; anti-galcanezumab antibodies with neutralizing activity were detected in 32 of the 33 patients (97%).1 In an open-label study of 12 months' duration, anti-galcanezumab antibodies were detected in up to 12.5% of galcanezumab-treated patients, most of whom had anti-galcanezumab antibodies with neutralizing activity.1 Although available data do not demonstrate an effect of anti-galcanezumab antibody development on the pharmacokinetics, efficacy, or safety of the drug, the data are too limited to make definitive conclusions.1

Specific Populations

Pregnancy

There are no adequate data on the developmental risk associated with the use of galcanezumab in pregnant females.1 Animal studies in pregnant rats and rabbits administered galcanezumab subcutaneously throughout the period of organogenesis or to rats throughout pregnancy at systemic exposures greater than those expected clinically have not revealed evidence of harm to the offspring.1

The estimated rate of major birth defects and miscarriage among deliveries to women with migraine (2.2-2.9 and 17%, respectively) are similar to rates reported in women without migraine.1 Clinicians should be aware that published data suggest that females with migraine may be at an increased risk of vascular complications such as preeclampsia during pregnancy.1,20 The long elimination half-life of galcanezumab should be considered if the drug is used in females who are pregnant or plan to become pregnant during therapy.20

There is a pregnancy exposure registry that monitors fetal outcomes in females exposed to galcanezumab during pregnancy.1 Healthcare providers are encouraged to register patients by calling the pregnancy exposure registry at 833-464-4724 or by visiting [Web].1

Lactation

It is not known whether galcanezumab is distributed into human milk.1 The effects of the drug on the breast-fed infant or on milk production also are unknown.1 The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for galcanezumab and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.1

Pediatric Use

Safety and efficacy of galcanezumab have not been established in pediatric patients.1 A clinical study to evaluate the efficacy and safety of galcanezumab in the preventive treatment of episodic migraine in pediatric patients 6-17 years of age† is currently under way.21

Pending further clinical experience with the use of anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies in pediatric patients, the Pediatric and Adolescent Headache special interest group of the American Headache Society (AHS) recommends that anti-CGRP monoclonal antibodies (e.g., erenumab, fremanezumab, galcanezumab) should be considered mainly for use in postpubertal adolescents† with relatively frequent migraines (i.e., 8 or more headache days per month) who have moderate to severe disability associated with migraine (e.g., Pediatric Migraine Disability Assessment [PedMIDAS] score of 30 or more) and in whom at least 2 preventive therapies (including pharmacologic and nonpharmacologic therapies and dietary supplements) have failed.11 For younger pediatric patients† with severe chronic migraine that is refractory to multiple preventive therapies, these experts recommend that anti-CGRP monoclonal antibodies be considered only in carefully selected patients with close monitoring (e.g., pubertal status, bone health, linear growth, weight, body mass index [BMI], infectious complications).11

Geriatric Use

Clinical trials of galcanezumab did not include sufficient numbers of patients 65 years of age or older to determine whether they respond differently than younger adults.1

Hepatic Impairment

Hepatic impairment is not expected to affect pharmacokinetics of galcanezumab.1,5,19 Formal pharmacokinetic studies of the drug have not been conducted in patients with hepatic impairment.1 Analysis of population pharmacokinetic data indicates that clearance of galcanezumab is not substantially affected by serum bilirubin concentration (an indirect marker of hepatic function).1,5,19

Renal Impairment

Renal impairment is not expected to affect pharmacokinetics of galcanezumab.1 Formal pharmacokinetic studies of the drug have not been conducted in patients with renal impairment.1 Analysis of population pharmacokinetic data indicates that creatinine clearance does not affect the pharmacokinetics of galcanezumab in patients with mild or moderate renal impairment.1,19 Galcanezumab has not been evaluated in patients with severe renal impairment (creatinine clearance less than 30 mL/minute).1

Common Adverse Effects

Adverse effects reported in 2% or more of patients receiving galcanezumab for the preventive treatment of migraine in clinical studies and at least 2% more frequently than with placebo include injection site reactions (e.g., pain, erythema, pruritus, swelling),1,2,3,4,6 which were usually mild to moderate in severity and resolved within a few days to 2 weeks.2,3,4,6

The tolerability profile of galcanezumab in patients with episodic cluster headache is consistent with the tolerability profile observed in migraine patients.1

Formal drug interaction studies with galcanezumab have not been conducted to date.5 The risk of clinically important drug interactions with galcanezumab appears to be minimal.1,5,12 Galcanezumab is not metabolized by cytochrome P-450 (CYP) enzymes.1 In addition galcanezumab, a monoclonal antibody, is not likely to be affected by drug transport systems.5 Therefore, pharmacokinetic interactions with drugs affecting or metabolized by CYP enzymes or substrates of various drug transport systems are not expected.1,5,12

Description

Galcanezumab is a humanized immunoglobulin G₄ (IgG₄) monoclonal antibody that binds to the calcitonin gene-related peptide (CGRP) ligand and blocks its binding with the CGRP receptor.1,9,10 The drug is produced using recombinant DNA technology in Chinese hamster ovary cells.1

CGRP is a potent vasodilator and pain-signaling neuropeptide that has been associated with migraine pathophysiology.8,9,10,18 CGRP and its receptors are located at sites that are relevant to migraine development such as the trigeminal neurons and are also widely distributed throughout the central and peripheral nervous systems as well as in nonneuronal tissues throughout the body.8,9,10,11,18

Increased serum CGRP concentrations have been observed in individuals during acute migraine attacks (with or without aura) and IV infusion of CGRP has been shown to induce migraines in patients with a history of migraines.8,9,10,18 Galcanezumab binds to the CGRP ligand and blocks its interaction with the CGRP receptor.1,9,10 Animal studies indicate possible limited distribution of galcanezumab into the CNS and cerebrospinal fluid.19 Because of their large molecular size, however, anti-CGRP monoclonal antibodies are considered unlikely to cross the blood-brain barrier in substantial amounts and probably antagonize CGRP function peripherally rather than centrally within the nervous system.11,13,18

The pharmacokinetics of galcanezumab appear to be similar in healthy individuals, patients with episodic or chronic migraine, and patients with episodic cluster headache.1 The drug exhibits linear and dose-proportional pharmacokinetics over a dosage range of 1-600 mg when given by subcutaneous injection.1,5 Following a 240-mg loading dose given subcutaneously, steady-state concentrations of galcanezumab are achieved after the first dose.1 When 300 mg of the drug is given subcutaneously once monthly, steady-state concentrations are achieved following the fourth dose.1 Peak plasma concentrations occur approximately 5 days following subcutaneous doses of galcanezumab.1,5 Antimigraine effects of anti-CGRP monoclonal antibodies, including galcanezumab, usually are evident following 1-3 monthly subcutaneous injections of the drug in responding patients.2,3,4,12 Galcanezumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.1 The elimination half-life of galcanezumab is approximately 27 days.1

Population pharmacokinetic analysis indicates that the pharmacokinetics of galcanezumab are not affected by age, sex, race, subtypes of migraine spectrum (e.g., episodic or chronic migraine), or headache diagnosis (e.g., migraine, episodic cluster headache).1,5 Body weight does not have a clinically important effect on the pharmacokinetics of the drug.1,5

Advice to Patients

• Advise patients to read the manufacturer's patient information and to read and follow the instructions for use each time they use galcanezumab.1
• Provide guidance to patients and/or caregivers on proper sub-Q administration of galcanezumab, including the use of aseptic technique and how to use the single-dose prefilled syringes or auto-injectors.1
• If a dose of galcanezumab for the preventive treatment of migraine is missed, administer the missed dose as soon as possible.1 Schedule subsequent doses monthly from the date of the last administered dose.1
• If a dose of galcanezumab for the treatment of episodic cluster headache is missed, administer the missed dose as soon as possible.1 If the cluster headache period has not yet ended, schedule subsequent doses monthly from the date of the last administered dose until the end of the cluster period.1
• Inform patients of possible signs and symptoms of hypersensitivity reactions (e.g., rash, urticaria, dyspnea), which can occur days after administration and may be prolonged.1 Patients should seek immediate medical attention if symptoms of a serious or severe hypersensitivity reaction occur.1
• Inform clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1
• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Advise patients that there is a pregnancy exposure registry that monitors fetal outcomes in females exposed to galcanezumab during pregnancy.1
• Inform patients of other important precautionary information.1

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

1. Eli Lilly and Company. Emgality^® (galcanezumab-gnlm) injection, for subcutaneous use prescribing information. Indianapolis, IN; 2021 Mar. [Web]

2. Stauffer VL, Dodick DW, Zhang Q et al. Evaluation of galcanezumab for the prevention of episodic migraine: the EVOLVE-1 randomized clinical trial. JAMA Neurol . 2018; 75:1080-1088. [PubMed 29813147]

3. Skljarevski V, Matharu M, Millen BA et al. Efficacy and safety of galcanezumab for the prevention of episodic migraine: Results of the EVOLVE-2 phase 3 randomized controlled clinical trial. Cephalalgia . 2018; 38:1442-1454. [PubMed 29848108]

4. Detke HC, Goadsby PJ, Wang S et al. Galcanezumab in chronic migraine: The randomized, double-blind, placebo-controlled REGAIN study. Neurology . 2018; 91:e2211-e2221. [PubMed 30446596]

5. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 761063Orig1s000: Clinical pharmacology and biopharmaceutics review(s). From FDA website. [Web]

6. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 761063Orig1s000: Summary review. From FDA website. [Web]

7. Camporeale A, Kudrow D, Sides R et al. A phase 3, long-term, open-label safety study of galcanezumab in patients with migraine. BMC Neurol . 2018; 18:188. [PubMed 30413151]

8. Shi L, Lehto SG, Zhu DX et al. Pharmacologic characterization of AMG 334, a potent and selective human monoclonal antibody against the calcitonin gene-related peptide receptor. J Pharmacol Exp Ther . 2016; 356:223-31. [PubMed 26559125]

9. Edvinsson L, Haanes KA, Warfvinge K et al. CGRP as the target of new migraine therapies - successful translation from bench to clinic. Nat Rev Neurol . 2018; 14:338-350. [PubMed 29691490]

10. Schuster NM, Rapoport AM. Calcitonin gene-related peptide-targeted therapies for migraine and cluster headache: A review. Clin Neuropharmacol . 2017 Jul/Aug; 40:169-174. [PubMed 28644160]

11. Szperka CL, VanderPluym J, Orr SL et al. Recommendations on the use of anti-CGRP monoclonal antibodies in children and adolescents. Headache . 2018; 58:1658-69. [PubMed 30324723]

12. American Headache Society. The American Headache Society position statement on integrating new migraine treatments into clinical practice. Headache . 2019; 59:1-18. [PubMed 30536394]

13. Raffaelli B, Reuter U. The biology of monoclonal antibodies: focus on calcitonin gene-related peptide for prophylactic migraine therapy. Neurotherapeutics . 2018; 15:324-35. [PubMed 29616494]

14. Eli Lilly and Company. Dear Health Care Professional letter regarding traveling with Emgality. Indianapolis, IN. 2019 Feb 27.

15. US Food and Drug Administration. FDA news release: FDA approves first treatment for episodic cluster headache that reduces the frequency of attacks. From FDA website. 2019 Jun 4. [Web]

16. Rozen TD, Fishman RS. Cluster headache in the United States of America: Demographics, clinical characteristics, triggers, suicidality, and personal burden. Headache . 2012; 52:99-113. [PubMed 22077141]

17. International Headache Society. Headache Classification Committee of the International Headache Society (IHS): The International Classification of Headache Disorders, 3rd edition. Cephalgia . 2018; 38:1-211. [PubMed 29368949]

18. Edvinsson L. The trigeminovascular pathway: role of CGRP and CGRP receptors in migraine. Headache . 2017; 57:47-55. [PubMed 28485848]

19. 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. Cephalgia . 2019; 0:1-14 [epub; ahead of print]. [PubMed 30917684]

20. Anon. Fremanezumab (Ajovy) and galcanezumab (Emgality) for migraine prevention. Med Lett Drugs Ther . 2018; 60:177-180. [PubMed 30681655]

21. U.S. National Library of Medicine. A study of galcanezumab (LY2951742) in participants 6 to 17 years of age with episodic migraine (REBUILD). From ClinicalTrials.gov website. 2019 Feb 19. [Web]

22. Goadsby PJ, Dodick DW, Leone M et al. Trial of Galcanezumab in Prevention of Episodic Cluster Headache. N Engl J Med . 2019; 381:132-141. [PubMed 31291515]

23. Ailani J, Burch RC, Robbins MS et al. The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache . 2021; 61:1021-1039. [PubMed 34160823]

24. Charles AC, Digre KB, Goadsby PJ, et al. Calcitonin gene-related peptide-targeting therapies are a first-line option for the prevention of migraine: an American Headache Society position statement update. Headache. 2024;1-9. [Web]