Galcanezumab for episodic and chronic cluster headache

Background Cluster headache (CH) is a highly debilitating headache disorder characterized by frequent attacks of excruciating unilateral pain accompanied by cranial autonomic symptoms. Calcitonin gene-related peptide (CGRP) is implicated in the pathophysiology of CH. Objectives Preventive efficacy and tolerability of the anti-CGRP antibody galcanezumab in patients with episodic (eCH) and chronic CH (cCH). Review of the study results and the challenges in developing drugs for the preventive treatment of CH. Materials and methods In two international multicenter phase III trials galcanezumab 300 mg given subcutaneously every 4 weeks was compared with placebo. The double-blind study period (8 weeks in eCH, 12 weeks in cCK) was preceded by a baseline period in both trials. The primary endpoint was the reduction in weekly attack frequency. Results In the eCH trial, 106 patients were randomized to either galcanezumab (n = 49) or placebo (n = 57). The mean weekly attack frequency during the first 3 weeks decreased by 52% in the galcanezumab group compared with 27% in the placebo group (p = 0.036). In the cCH trial, 237 patients were randomized to galcanezumab (n = 117) or placebo (n = 120). The primary endpoint was not met in this study. The reduction in mean weekly attack rate was 5.4 with galcanezumab versus 4.6 with placebo (p = 0.334). Galcanezumab was well tolerated in both studies. Conclusions Galcanezumab had a significant effect in the prevention of eCH attacks but not in cCH. Possible reasons for this discrepancy are discussed.