Introduction
Emgality (galcanezumab-gnlm) is a monoclonal antibody medication developed by Eli Lilly and Company. It belongs to the class of calcitonin gene-related peptide (CGRP) inhibitors specifically designed for migraine prevention. Approved by the FDA in September 2018, Emgality represents a significant advancement in migraine prophylaxis, offering a targeted mechanism of action for patients who have not responded adequately to conventional preventive therapies.
Mechanism of Action
Emgality is a humanized immunoglobulin G4 (IgG4) monoclonal antibody that selectively binds to calcitonin gene-related peptide (CGRP) ligand. CGRP is a neuropeptide widely distributed throughout the central and peripheral nervous systems that plays a crucial role in migraine pathophysiology. During migraine attacks, CGRP levels increase significantly, causing cerebral vasodilation, neurogenic inflammation, and pain transmission. By binding to CGRP, Emgality prevents its interaction with the CGRP receptor, thereby inhibiting the neurovascular events that lead to migraine attacks without causing vasoconstriction.
Indications
FDA-approved indications:
- Preventive treatment of migraine in adults
- Treatment of episodic cluster headache in adults
Dosage and Administration
Migraine Prevention:- Loading dose: 240 mg (two consecutive 120 mg injections) initially
- Maintenance dose: 120 mg administered subcutaneously once monthly
- Loading dose: 300 mg (three consecutive 100 mg injections) at cluster headache onset
- Maintenance dose: 100 mg administered subcutaneously once monthly during cluster period
- For subcutaneous injection only
- Prefilled syringe or autoinjector formats available
- May be administered in abdomen, thigh, back of upper arm, or buttock
- Rotate injection sites with each administration
- Allow medication to reach room temperature for 30 minutes before injection
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: No dosage adjustment necessary
- Geriatric patients: No dosage adjustment necessary
- Pregnancy: Category C - use only if potential benefit justifies potential risk
- Pediatrics: Safety and effectiveness not established
Pharmacokinetics
Absorption: Following subcutaneous administration, galcanezumab is absorbed with peak concentrations achieved in approximately 5 days. Bioavailability is approximately 85%. Distribution: Steady-state volume of distribution is approximately 7.3 L. Minimal distribution to red blood cells. Metabolism: Galcanezumab is metabolized via proteolytic enzymes into small peptides and amino acids, similar to endogenous IgG antibodies. Elimination: Elimination follows linear pharmacokinetics. Terminal half-life is approximately 27 days. Clearance occurs primarily through intracellular catabolism following fluid-phase or receptor-mediated endocytosis.Contraindications
- History of hypersensitivity reaction to galcanezumab-gnlm or any component of the formulation
- Serious hypersensitivity reactions, including anaphylaxis, have been reported
Warnings and Precautions
Hypersensitivity Reactions: May occur with Emgality, including dyspnea, rash, urticaria, and anaphylaxis. Most reactions occur within hours of administration but may be delayed. Discontinue immediately if serious hypersensitivity reaction occurs. Injection Site Reactions: Erythema, pain, pruritus, and swelling may occur. Typically mild to moderate and resolve within several days. Immunogenicity: As with all therapeutic proteins, there is potential for immunogenicity. Anti-drug antibodies developed in approximately 4.8% of patients in clinical trials, though clinical significance remains unclear.Drug Interactions
No formal drug interaction studies have been conducted. However, based on its mechanism of action:
- Theoretical potential for interactions with other CGRP antagonists
- No expected interactions with cytochrome P450 substrates
- No pharmacokinetic interactions anticipated with commonly prescribed migraine medications including triptans, NSAIDs, or acetaminophen
Adverse Effects
Most Common Adverse Reactions (≥2% and more frequent than placebo):- Injection site reactions (pain, erythema, pruritus)
- Sinusitis
- Upper respiratory tract infection
- Hypersensitivity reactions including anaphylaxis
- Constipation (reported in post-marketing surveillance)
Monitoring Parameters
- Frequency and severity of migraine attacks (use headache diary)
- Injection site reactions
- Signs of hypersensitivity reactions following administration
- Patient-reported functional impairment and quality of life measures
- Liver function tests (if clinically indicated)
- Anti-drug antibody formation (in cases of treatment failure or hypersensitivity)
Patient Education
Administration Instructions:- Demonstrate proper injection technique using training materials
- Instruct on rotation of injection sites
- Teach recognition and management of injection site reactions
- Emphasize importance of monthly dosing adherence
- Recognize signs of hypersensitivity reactions (rash, hives, swelling, difficulty breathing)
- Seek immediate medical attention for serious allergic reactions
- Inform healthcare providers about all medications being taken
- Full effect may take up to 3 months of continuous treatment
- Continue medication even if migraine frequency decreases
- Maintain headache diary to track effectiveness
- Report any new or worsening symptoms to healthcare provider
- Refrigerate at 2°C to 8°C (36°F to 46°F)
- Do not freeze
- Protect from light
- May be stored at room temperature up to 30°C (86°F) for up to 7 days
References
1. FDA Prescribing Information: Emgality (galcanezumab-gnlm) injection. September 2018. 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(9):1080-1088. 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(8):1442-1454. 4. Detke HC, Goadsby PJ, Wang S, et al. Galcanezumab in chronic migraine: the randomized, double-blind, placebo-controlled REGAIN study. Neurology. 2018;91(24):e2211-e2221. 5. Goadsby PJ, Dodick DW, Leone M, et al. Trial of galcanezumab in episodic cluster headache. N Engl J Med. 2019;381(2):132-141. 6. 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(1):188.