Galcanezumab is a subcutaneously administered calcitonin gene-related peptide (CGRP) antagonist indicated for migraine prophylaxis and treatment of episodic cluster headache in adults. In clinical trials of subjects with episodic migraine, monthly migraine days were significantly reduced from baseline by 4.3 to 4.7 days at 6 months in galcanezumab-treated subjects in comparison to 2.3 to 2.8 days for placebo. At month 3, galcanezumab-treated chronic migraine subjects experienced a significant 4.8-day reduction from baseline in monthly migraine days vs. placebo. A 50% or greater reduction in monthly migraine days was achieved by 59% to 62% of episodic migraineurs and 28% of chronic migraineurs who were treated with galcanezumab compared to 36% to 39% of episodic migraineurs and 15% of chronic migraineurs given placebo. Cluster headache attack frequency was significantly reduced from baseline by 8.7 days at week 3 in galcanezumab-treated subjects in comparison to 5.2 days for placebo. A reduction from baseline of 50% or more in weekly cluster headache attack frequency was achieved by 71.4% of galcanezumab-treated subjects compared to 52.6% for placebo. Hypersensitivity reactions, including dyspnea, urticaria, and rash, have occurred with galcanezumab in clinical studies and the postmarketing setting. Cases of anaphylaxis and angioedema have also been reported in the postmarketing setting. Hypersensitivity reactions can occur days after administration and may be prolonged.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use if the galcanezumab solution is cloudy or discolored or has small particles. Galcanezumab is a clear to opalescent, colorless to slightly yellow to slightly brown solution.
Subcutaneous Administration
-Galcanezumab is intended for self-administration. Provide proper training to individuals and/or caregivers on how to prepare and administer galcanezumab, including aseptic technique.
-Prior to administration, allow galcanezumab to sit at room temperature for at least 30 minutes protected from direct sunlight. Do not warm using a heat source such as hot water or microwave.
-Do not shake.
-Clean injection site on the abdomen, thigh, back of the upper arm, or buttocks with an alcohol wipe, and allow skin to dry.
-Do not inject into areas where the skin is tender, bruised, red, or hard.
-If using the same body area for more than 1 injection per dose, ensure each subsequent injection is not at same location as previous injection.
-If a dose is missed, give the next dose as soon as possible. Subsequently, schedule from the date of the last dose.
-Discard the prefilled pen or syringe in a FDA-cleared sharps disposal container. Do not discard in household trash.
-Storage: After removing galcanezumab from the refrigerator, it can be stored in the original carton at room temperature up to 86 degrees F (30 degrees C) for up to 7 days. Do not return galcanezumab to the refrigerator after it has reached room temperature.
Single-dose, Prefilled Pen
-Twist off the base cap and throw it away in trash.
-Place and hold the clear base flat and firmly against skin.
-Turn the lock ring to the unlock position.
-Press and hold the teal injection button; a loud click will be heard. The injection could take about 10 seconds. When the injection is complete, a click will be heard.
-Remove the pen from the skin.
Single-dose, Prefilled Syringe
-Pull needle cap off and throw it away in trash.
-Gently pinch and hold injection site skin.
-Insert the needle into skin at a 45-degree angle.
-Using slow and constant pressure, push the plunger rod all the way down with thumb until the prefilled syringe stops moving.
-Remove needle from skin, and gently let go of skin.
An injection site reaction, including injection site pain, injection site erythema, or injection site pruritus, was the most frequent adverse reaction reported during 3 double-blind, placebo-controlled studies of galcanezumab in adults with migraines. Injection site reactions occurred in 18% of subjects who received at least 1 dose of 120 mg once monthly during 3 or 6 months of double-blind treatment (n = 705). Injection site reactions were reported in 13% of placebo-treated subjects (n = 1,451). Overall, the safety profile observed in subjects with episodic cluster headache treated with galcanezumab 300 mg monthly is consistent with the safety profile in migraine subjects.
Hypersensitivity reactions (e.g., rash, urticaria, and dyspnea) have been reported with galcanezumab during clinical trials of adults with migraines and during postmarketing experience. Angioedema and anaphylactoid reactions have also been reported during postmarketing experience. Overall, the safety profile observed in subjects with episodic cluster headache treated with galcanezumab 300 mg monthly is consistent with the safety profile in migraine subjects. If a serious hypersensitivity reaction occurs, discontinue galcanezumab and initiate appropriate treatment. Hypersensitivity reactions can occur days after galcanezumab administration and may be prolonged.
As with all therapeutic proteins, there is the potential for immunogenicity and antibody formation. In clinical trials of galcanezumab in adults with migraines, anti-galcanezumab antibodies developed in 4.8% (33/688) of subjects who received galcanezumab 120 mg once monthly (32 of whom had in vitro neutralizing activity). Within 12 months of treatment in an open-label study, up to 12.5% (16/128) of galcanezumab-treated subjects developed anti-galcanezumab antibodies; most subjects tested positive for neutralizing antibodies. Although the data did not demonstrate an impact of anti-galcanezumab antibody development on the efficacy or safety of galcanezumab, data are too limited to make definitive conclusions. Overall, the safety profile observed in subjects with episodic cluster headache treated with galcanezumab 300 mg monthly is consistent with the safety profile in migraine subjects.
Constipation was reported with galcanezumab in postmarketing experience.
Alopecia was reported with galcanezumab in postmarketing experience.
There are no adequate data on the developmental risk associated with galcanezumab use during human pregnancy. No adverse developmental effects were observed when rats and rabbits were given galcanezumab throughout organogenesis at exposures approximately 38 to 64-times the recommended human dose (RHD) of 120 mg. Administration of galcanezumab to rats throughout pregnancy and lactation produced no adverse effects on pre- and postnatal development at exposures up to 34-times the RHD. Persons with migraine may be at increased risk of preeclampsia during pregnancy. There is a pregnancy exposure registry that monitors outcomes in persons exposed to galcanezumab during pregnancy. Healthcare providers are encouraged to register pregnant persons, or pregnant persons may enroll themselves in the registry by calling 1-833-464-4724 or visiting www.migrainepregnancyregistry.com.
There are no data on the presence of galcanezumab in human milk, the effects on the breast-fed infant, or the effects on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for galcanezumab and any potential adverse effects on the breast-fed infant from galcanezumab or the underlying maternal condition.
Guideline indications for initiating migraine prevention with monoclonal antibodies to calcitonin gene-related peptide (CGRP) or its receptor:
-Migraine with or without aura (4 to 7 monthly headache days) and inability to tolerate or inadequate response to an 8-week trial of at least 2 evidence-based preventative treatments and at least moderate disability defined by Migraine Disability Assessment Score (MIDAS) more than 11 or Headache Impact Test Score (HIT-6) more than 50
-Migraine with or without aura (8 to 14 monthly headache days) and inability to tolerate or inadequate response to an 8-week trial of at least 2 evidence-based preventative treatments
-Chronic migraine and inability to tolerate or inadequate response to an 8-week trial of at least 2 evidence-based preventative treatments or inability to tolerate or inadequate response to a minimum of 2 quarterly injections (6 months) of onabotulinumtoxinA
Evidence-based migraine preventative treatments with established or probable efficacy include:
-Topiramate
-Divalproex sodium/valproate sodium
-Beta-blocker: metoprolol, propranolol, timolol, atenolol, nadolol
-Tricyclic antidepressant: amitriptyline, nortriptyline
-Serotonin-norepinephrine reuptake inhibitor: venlafaxine, duloxetine
Guideline criteria for continuation of migraine prevention with monoclonal antibodies to CGRP or its receptor after 3 months or more (monthly dosing):
-Reduction in mean monthly headache days of 50% or more relative to pretreatment baseline (diary documentation or healthcare provider attestation) or
-Clinically meaningful improvement, defined by MIDAS reduction of 5 points or more with a baseline score of 11 to 20 or reduction of 30% or more with baseline score more than 20, HIT-6 reduction of 5 points or more, or Migraine Physical Function Impact Diary (MPFID) reduction of 5 points or more
For migraine prophylaxis:
Subcutaneous dosage:
Adults: 240 mg subcutaneously once as a loading dose, followed by 120 mg subcutaneously once monthly. Guidelines classify galcanezumab as having established efficacy for migraine prophylaxis.
For the treatment of episodic cluster headache:
Subcutaneous dosage:
Adults: 300 mg subcutaneously at the onset of the cluster period and once monthly until the end of the cluster period.
Maximum Dosage Limits:
-Adults
300 mg/month subcutaneously.
-Geriatric
300 mg/month subcutaneously.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
There are no drug interactions associated with Galcanezumab products.
Galcanezumab is a humanized immunoglobulin G4 (IgG4) monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor. CGRP is distributed throughout the nervous system, and it is concentrated at anatomical sites, such as the trigeminovascular system, which are involved in migraine pathophysiology. Centrally, CGRP is involved in nociceptive transmission through second and third order neurons and pain modulation in the brainstem. Peripherally, CGRP mediates vasodilation through smooth muscle receptors. CGRP concentrations are elevated during acute migraine attacks and may be chronically elevated in chronic migraineurs.
Galcanezumab is administered subcutaneously. Galcanezumab exhibits linear kinetics. A loading dose of 240 mg achieved serum galcanezumab steady-state concentration after the first dose. A dose of 300 mg monthly would achieve steady-state concentration after the fourth dose. The apparent volume of distribution is 7.3 L (34% interindividual variability). Galcanezumab is degraded into small peptides and amino acids by catabolic pathways in the same manner as endogenous immune globulin. Galcanezumab apparent clearance is 0.008 L/hour. The half-life of galcanezumab is approximately 27 days.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Subcutaneous Route
After a subcutaneous galcanezumab dose, the time to maximum concentration is approximately 5 days. Injection site location did not significantly affect the absorption of galcanezumab.
-Special Populations
Hepatic Impairment
Hepatic impairment is not expected to affect the clearance of galcanezumab. Based on a population pharmacokinetic analysis, bilirubin concentration did not significantly influence the CL/F of galcanezumab.
Renal Impairment
Renal impairment is not expected to affect the clearance of galcanezumab. Creatinine clearance (CrCl) did not affect the pharmacokinetics of galcanezumab in persons with mild or moderate renal impairment. Persons with severe renal impairment (CrCl less than 30 mL/minute) have not been studied.
Geriatric
The pharmacokinetics of galcanezumab were not affected by age.
Gender Differences
The pharmacokinetics of galcanezumab were not affected by gender.
Ethnic Differences
The pharmacokinetics of galcanezumab were not affected by race.
Other
Headache Diagnosis or Migraine Spectrum Subtype
The pharmacokinetics of galcanezumab were not affected by headache diagnosis (migraine vs. episodic cluster headache) or migraine spectrum subtype (episodic or chronic migraine).