What is Galcanezumab?

What is Galcanezumab?

Galcanezumab is a humanized monoclonal antibody that binds directly to the calcitonin gene-related peptide (CGRP) ligand, preventing it from activating its receptor, and is FDA-approved for the preventive treatment of migraine and episodic cluster headache. 1

Mechanism of Action

• Galcanezumab works by neutralizing free CGRP, a protein that plays a critical role in trigeminal nerve pain and inflammation during migraine and cluster headache attacks 2, 1
• Unlike erenumab (which blocks the CGRP receptor itself), galcanezumab binds to the CGRP peptide ligand, reducing the amount of bioavailable CGRP that can activate pain pathways 3
• The drug is produced in Chinese Hamster Ovary (CHO) cells and is composed of two identical immunoglobulin kappa light chains and two identical immunoglobulin gamma heavy chains, with a molecular weight of approximately 147 kDa 1

Pharmacokinetics

• Administration: Subcutaneous injection with time to maximum concentration of approximately 5 days 1
• Dosing: A loading dose of 240 mg achieves steady-state concentration after the first dose; maintenance dosing of 120 mg monthly maintains steady state 1
• Half-life: Approximately 27 days, allowing for monthly dosing 1
• Metabolism: Degraded into small peptides and amino acids via catabolic pathways like endogenous IgG, not metabolized by cytochrome P450 enzymes 1

Clinical Indications and Evidence

Migraine Prevention

• The 2023 VA/DoD guidelines suggest galcanezumab for prevention of episodic and chronic migraine, though the specific recommendation strength is not explicitly stated for galcanezumab in migraine (the guidelines group it with other CGRP monoclonal antibodies). 2
• Galcanezumab at both 120 mg and 240 mg dosages reduces monthly migraine days by approximately 1.86-1.98 days compared to placebo 4, 5
• The 120 mg dose has equivalent efficacy to the 240 mg dose but with a lower risk of adverse events, making it the preferred maintenance dose 4
• Treatment response (≥50% reduction in migraine frequency) occurs in approximately 51-58% of patients 4

Cluster Headache Prevention

• The 2023 VA/DoD guidelines suggest galcanezumab for prevention of episodic cluster headache (weak for recommendation) but suggest against it for chronic cluster headache (weak against recommendation). 2
• For episodic cluster headache, 300 mg monthly (or 240 mg using two 120 mg syringes) is effective, with 78.8% of patients achieving ≥50% reduction in weekly attacks at week 3 4, 6
• The median time to 100% reduction in cluster headache attacks is approximately 17 days after galcanezumab administration 6
• Real-world evidence supports using 240 mg (two 120 mg syringes) when the 100 mg formulation is unavailable, with similar efficacy to the FDA-approved 300 mg dose 6

Formulations and Dosing

• Available as: 1 mL single-dose prefilled pen (120 mg) or prefilled syringe (100 mg or 120 mg) 1
• For migraine: Loading dose of 240 mg, then 120 mg monthly 1
• For episodic cluster headache: 300 mg monthly during the cluster period (or 240 mg using two 120 mg syringes) 6

Safety Profile

• Most adverse events are mild to moderate, with low rates of serious adverse events and discontinuation 5, 7
• Common adverse events include injection site reactions, but these rarely lead to treatment discontinuation 4, 8
• Important distinction: Unlike erenumab (another CGRP-targeting antibody), galcanezumab does not carry the same hypertension risk because it targets the ligand rather than the receptor 3, 9
• No significant drug interactions expected as it is not metabolized by cytochrome P450 enzymes 1

Population Considerations

• Pharmacokinetics are not affected by age, sex, race, ethnicity, body weight, or headache subtype (episodic vs. chronic migraine, migraine vs. cluster headache) 1
• Renal and hepatic impairment are not expected to affect pharmacokinetics, though severe renal impairment (creatinine clearance <30 mL/min) has not been studied 1