Galcanezumab for Episodic Migraine
Published online Dec. 18, 2017
Current medications for migraine have variable efficacy, low adherence, and considerable adverse events (AEs). Recent studies have shown that calcitonin gene-related peptide is involved in migraine pathophysiology, which has prompted interest in monoclonal antibodies such as galcanezumab as preventive therapy. In a phase 2b trial, Skljarevski et al. compared various monthly doses of galcanezumab with placebo and found that the 120-mg dose of the drug was well tolerated and reduced migraine frequency.
The trial was conducted in 2014 and 2015 by 37 physicians in the United States. It consisted of 4 periods: screening/washout, prospective baseline (to determine migraine headache days [MHDs]), double-blind treatment, and post-treatment. The primary endpoint was superiority to placebo, evidenced by reduction in MHDs, from baseline to 9 or 12 weeks. Short-term migraine treatments—excluding opioids and barbiturates—were permitted during the trial.
The 410 enrollees (83% female) had onset of episodic migraine before 50 years of age and were experiencing 4 to 14 MHDs per month. Participants were assigned randomly (2:1:1:1:1) to receive monthly subcutaneous injection of placebo or galcanezumab (5, 50, 120, or 300 mg) for 3 months.
Period 3 of the trial was completed by 375 patients (galcanezumab, n = 249; placebo, n = 126). By month 3 of treatment, the 120-mg dose of galcanezumab had significantly reduced MHDs (‒4.8 MHDs; ‒5.4 to ‒4.2 MHDs) versus placebo (‒3.7 MHDs; ‒4.1 to ‒3.2 MHDs). From baseline to month 3, both the 120- and 300-mg doses of galcanezumab were more effective than placebo in reducing the overall number of MHDs. The frequency of treatment-emergent AEs was comparable for active-treatment groups. The most common AEs were upper respiratory tract infection, pain at the injection site, nasopharyngitis, nausea, and dysmenorrhea.
The authors cautioned that the small sample size precludes definitive conclusions about the safety of galcanezumab. However, they encouraged phase 3 investigation of varying doses of the drug to further assess its safety and efficacy for episodic migraine.
The original article can be found here.