By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved the first drug to reduce the frequency of episodic cluster headache. Galcanezumab is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand, blocking its binding to the CGRP receptor. Researchers believe CGRP plays an active role in migraine and cluster headaches. Galcanezumab was approved in September 2018 for the prevention of migraine headaches. It is distributed as Emgality.
Galcanezumab is indicated for the preventive treatment of migraine and treatment of episodic cluster headache.1
The recommended dose for episodic cluster headache is 300 mg (three consecutive subcutaneous injections of 100 mg) at the onset of the cluster period and then monthly until the end of the cluster period.1 Sites of administration include the abdomen, thigh, back of upper arm, or buttocks. Galcanezumab is available as a 100 mg/mL single-dose, prefilled syringes as well as 120 mg/mL prefilled pens and syringes.
In addition to providing a new mechanism of action, galcanezumab also is the first FDA-approved drug to reduce the frequency of episodic cluster headaches.
The most common adverse reaction is injection site reactions (e.g., pain, erythema, and pruritus).1 The incidence of anti-galcanezumab antibodies ranges from 4.8% to 12.5% after six to 12 months of treatment, respectively.1 These are mostly neutralizing antibodies. The clinical significance is unclear at this time.1
The efficacy of galcanezumab was evaluated in a randomized, eight-week, double-blind, placebo-controlled study. Subjects included those with episodic cluster headache who experienced a maximum of eight attacks per day, a minimum of one attack every other day, and at least four attacks during the prospective seven-day baseline period.1 Subjects were excluded if they showed ECG abnormalities or presented with a history of myocardial infarction, unstable angina, cardiac procedures (percutaneous transluminal coronary angioplasty, bypass grafting), deep vein thrombosis, pulmonary embolism, stroke, intracranial or carotid aneurysm, peripheral vascular disease, or Raynaud’s disease. Subjects were randomized to either galcanezumab (n = 49) or placebo (n = 57). Certain rescue medications, such as triptans, oxygen, acetaminophen, or nonsteroidal anti-inflammatory drugs, were permitted. The primary efficacy endpoint was the mean change from baseline in weekly cluster headache attack frequency across week 1 to week 3. The secondary endpoint was the percentage of subjects achieving a 50% reduction (responders) in frequency of weekly cluster attack at week 3. Galcanezumab showed a mean 49% reduction from a baseline frequency of 17.8% compared to a 30% reduction from a baseline of 17.3% for placebo (P = 0.036). Responder rates were 71.4% vs. 52.6% (P = 0.046).
Cluster headache is a rare, extremely debilitating, trigeminal autonomic cephalgia.2,3 The estimated lifetime prevalence is about 0.12%, with higher prevalence in males. Episodic cluster headaches are more prevalent than the chronic type.3 Generally, cluster headache is more severe than migraine, but with shorter duration and accompanied by autonomic symptoms (e.g., watery eyes and runny nose). Cluster headaches may occur several times a day lasting between 15 minutes and three hours.2 Those with episodic headaches may experience freedom from headache for periods of months or years. Those with chronic headaches experience no remission or only enjoy a period free from headaches lasting less than one month.4
Currently, cluster headaches are not treated optimally. The American Headache Society Evidence-Based Guidelines and The American Academy of Neurology quality criteria recommend subcutaneous sumatriptan, intranasal zolmitriptan, and high-flow oxygen for acute treatment.5,6 Sumatriptan injection, approved for acute treatment, provides headache relief in 75% of patients compared to 26-35% for placebo.7 There are no approved effective treatments for reducing the frequency of attacks prior to galcanezumab, although suboccipital corticosteroid injection has established effectiveness off-label.5 Galcanezumab, as well as fremanezumab (the other FDA-approved CGRP ligand monoclonal antibody), have not shown efficacy in preventing chronic cluster headaches.8 The maker of fremanezumab recently terminated its study for the prevention of episodic cluster headache due to early indications of insufficient effectiveness.9 The cost of galcanezumab for 300 mg (3 × 100 mg) is $1,725.
- Eli Lilly and Company. Emgality Prescribing Information. Available at: . Accessed June 24, 2019.
- U.S Food & Drug Administration. FDA approves first treatment for episodic cluster headache that reduces the frequency of attacks, June 4, 2019. Available at: . Accessed June 24, 2019.
- Fischera M, Marziniak M, Gralow I, Evers S. The incidence and prevalence of cluster headache: A meta-analysis of population-based studies. Cephalgia 2008;28:614-618.
- American Migraine Foundation. Understanding Cluster Headache, April 18, 2019. Available at: . Accessed June 24, 2019.
- Robbins MS, Starling AJ, Pringsheim TM, et al. Treatment of cluster headache: The American Headache Society Evidence-Based Guidelines. Headache 2016;56:1093-1106.
- Francis GJ, Becker WJ, Pringsheim TM. Acute and preventive pharmacologic treatment of cluster headache. Neurology 2010;75:463-473.
- GlaxoSmithKline LLC. Imitrex Prescribing Information, July 2018. Available at: . Accessed June 24, 2019.
- Tepper SJ. Anti-calcitonin gene-related peptide (CGRP) therapies: Update on a previous review after the American Headache Society 60th Scientific Meeting, San Francisco, June 2018. Headache 2018;58 Suppl 3:276-290.
- Smith A. Teva abandons Ajovy trial for cluster headaches. PharmaTimes, April 24, 2019. Available at: . Accessed June 24, 2019.