Galcanezumab Reduces Attack Frequency in Patients With Cluster Headache

SAN FRANCISCO—Among patients with episodic cluster headache, galcanezumab significantly reduced weekly attack frequency, according to the results of a phase III trial presented at the 60th Annual Scientific Meeting of the American Headache Society. Results of an eight-week, double-blind, placebo-controlled clinical trial showed that galcanezumab (300 mg SC) significantly reduced the weekly cluster headache attack frequency across weeks one to three, which was the study’s primary end point, and resulted in a significantly greater percentage of patients achieving a 50% or greater reduction in their weekly cluster headache attack frequency at week three.

James M. Martinez, MD, a medical fellow at Eli Lilly, Indianapolis, Indiana, and study collaborators sought to determine if galcanezumab (aka LY2951742), a humanized monoclonal antibody that selectively binds to calcitonin gene-related peptide (CGRP), is efficacious as a preventive treatment of episodic cluster headache.

A phase III study was designed to assess the efficacy and safety of galcanezumab in individuals with episodic cluster headache, as defined by ICHD-3 beta criteria. This study comprised a screening period; a prospective baseline period; an eight-week, double-blind, placebo-controlled treatment period; and a four-month posttreatment washout period.

In the double-blind treatment period, participants were randomized 1:1 to galcanezumab 300 mg SC (n = 49) or placebo (n = 57) once monthly for two months. The primary end point was the overall mean change from baseline in weekly cluster headache attack frequency across weeks one to three. The key secondary end point was the proportion of participants achieving a response, defined as a reduction from baseline of 50% or greater in the weekly cluster headache attack frequency at week three. Other secondary end points included proportion of participants very much or much better based on Patient Global Impression of Improvement (PGI-I) at weeks four and eight.

Baseline demographics of the galcanezumab and placebo groups were similar. Mean age was 47 and 45, respectively; 84% and 82%, respectively, were male. The mean number of weekly cluster headache attacks in the baseline period was 17.8 for the galcanezumab group and 17.3 for the placebo group. Overall, four participants (8%) in the galcanezumab treatment group discontinued therapy during the double-blind period versus 12 (21%) in the placebo group. In the placebo group, eight participants (14%) discontinued treatment due to lack of efficacy versus one (2%) in the galcanezumab group. The mean change in weekly cluster headache attack frequency across weeks one to three was –8.7 for galcanezumab versus –5.2 for placebo (difference between treatment groups in mean change, –3.5). The proportion of participants achieving a 50% or greater reduction in weekly cluster headache attack frequency was 76% for galcanezumab versus 57% for placebo. The proportion of participants very much or much better based on PGI-I was significantly greater with galcanezumab versus placebo at week four (73% vs 46%) but not at week eight (72% vs 66%). There were no clinically meaningful differences between treatment groups on tolerability or safety parameters except for a statistically significantly greater incidence of injection site pain with galcanezumab versus placebo (8.2% vs 0%), which was similar to the safety profile seen previously in patients with episodic and chronic migraine.

—Glenn S. Williams