Galcanezumab

Introduction to Galcanezumab

Galcanezumab (brand name: Emgality) is a humanized monoclonal antibody that targets the calcitonin gene-related peptide (CGRP) ligand. It was approved by the FDA in 2018 for the preventive treatment of migraine in adults and in 2019 for the treatment of episodic cluster headache in adults. Galcanezumab represents a significant advancement in migraine and cluster headache therapy, offering a targeted approach to prevention with monthly dosing.

Mechanism of Action

Galcanezumab works by:

  • Selectively binding to the CGRP ligand with high affinity
  • Preventing CGRP from binding to its receptor
  • Inhibiting CGRP-mediated vasodilation and neurogenic inflammation
  • Blocking CGRP-induced sensitization of trigeminal neurons
This mechanism effectively disrupts the migraine and cluster headache cascades, reducing the frequency and severity of attacks. Like fremanezumab, galcanezumab targets the CGRP ligand rather than its receptor.

Indications

Galcanezumab is primarily indicated for:

  • Preventive treatment of migraine in adults
  • Treatment of episodic cluster headache in adults
It is particularly beneficial for patients who have failed or are intolerant to other preventive treatments. The approval for cluster headache makes galcanezumab unique among CGRP antagonists.

Dosage and Administration

  • Available in pre-filled pens and syringes
  • For migraine prevention:
    • Initial loading dose of 240 mg (two consecutive 120 mg injections)
    • Followed by 120 mg monthly
  • For episodic cluster headache:
    • 300 mg (three consecutive 100 mg injections) at the onset of the cluster period
    • Then monthly until the end of the cluster period
  • Administered subcutaneously
  • Can be self-administered by patients after proper training
  • No dose adjustment required for renal or hepatic impairment

Efficacy

Clinical trials have demonstrated significant efficacy:

  • For migraine prevention:
    • Reduction in monthly migraine days by 4-5 days compared to placebo
    • 50% or greater reduction in monthly migraine days in about 60% of patients
    • Improvement in quality of life and disability scores
    • Onset of efficacy observed within the first month of treatment
  • For episodic cluster headache:
    • Significant reduction in weekly cluster headache attack frequency
    • Higher proportion of patients achieving ≥50% reduction in weekly cluster headache attack frequency
  • Sustained efficacy demonstrated in long-term studies (up to 1 year)

Safety and Adverse Effects

Galcanezumab is generally well-tolerated. Common adverse effects include:

  • Injection site reactions (pain, erythema, pruritus)
  • Nasopharyngitis
  • Mild to moderate upper respiratory tract infections
Less common but potential adverse effects may include:
  • Hypersensitivity reactions
  • Constipation
  • Vertigo
Long-term safety data is still being collected, but current evidence suggests a favorable safety profile. There have been rare reports of new-onset hypertension, which should be monitored.

Pediatric Considerations

While Galcanezumab is not currently approved for use in pediatric populations:

  • Clinical trials in adolescents (12-17 years) are ongoing (REBUILD study)
  • Preliminary data suggests a similar safety profile to adults
  • Efficacy in pediatric populations is still being evaluated
  • The potential for treating both migraine and cluster headache may be particularly advantageous in pediatric patients if approved
  • Off-label use in refractory cases has been reported in literature, but more research is needed
  • Pediatricians should closely monitor ongoing research and guidelines for potential future use in pediatric migraine and cluster headache prevention



Further Reading
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