Galcanezumab Improves Episodic Migraine In Patients With Prior Failures

Peter J. Goadsby, MD, PhD, DSc, professor of neurology at both the University of California San Francisco and Kings College, London

Peter J. Goadsby, MD, PhD, DSc

Galcanezumab (Emgality; Eli Lilly) has been observed to be successful in improving patients with episodic migraine, with the individuals who had failed ≥1 or ≥2 prior preventive agents. Similar results were also reported in those with no failures, though with a larger response from placebo.¹

Treatment with the calcitonin gene-related peptide (CGRP) inhibitor resulted in significant improvements in monthly migraine headache days across the groups assessed, including a significantly greater number of patients with ≥50% and ≥75% reductions.

Thus far, galcanezumab’s efficacy has been displayed in 2 pivotal trials in those with episodic migraine, EVOLVE-1 and EVOLVE-2. This integrated analysis, conducted by Peter J. Goadsby, MD, PhD, DSc, professor of neurology at both the University of California San Francisco and King’s College, London, and colleagues, assessed the agent among subgroups of patients for whom, previously, for efficacy and/or safety or tolerability reasons had 1 or more preventives fail, 2 or more preventives fail, and in whom preventives were never used, or were used but did not fail.

“The findings of this subgroup analysis in patients with episodic migraine are clinically relevant considering that the subgroups chosen here are consistent with the expected target population for galcanezumab based on current treatment guidelines,” Goadsby and colleagues wrote. “Galcanezumab, with its mechanism of action targeting the pathophysiology of migraine and favorable efficacy, may offer an effective treatment option for patients with episodic migraine who have failed prior preventives.”

READ MORE: Migraine Treatment With Galcanezumab Not Associated With Cardiovascular Events

All told, the study included 1773 patients, of which 894 were randomized to placebo while the remaining 444 and 435 were administered 120 mg and 240 mg doses of galcanezumab, respectively, and followed for 6 months. In total, 74.4% (n = 1319) had no prior failures (placebo: 75.2% [n = 672]; 120 mg: 71.2% [n = 316]; 240 mg: 76.1% [n = 331]), while 25.6% (n = 454) had ≥1 failure (placebo: 24.8% [n = 222]; 120 mg: 28.8% [n = 128]; 240 mg: 23.9% [n = 104]) and 10.6% (n = 188) had ≥2 failures (placebo: 10.3% [n = 92]; 120 mg: 11.5% [n = 51]; 240 mg: 10.3% [n = 45]).

The mean reduction in monthly migraine days for the 120 mg and 240 mg groups were significantly greater in those with prior failures (P <.0001). Those with ≥1 failure experienced a reduction of 4.0 days (standard error [SE], 0.4) with 120 mg galcanezumab and 4.2 days (SE, 0.5) with 240 mg galcanezumab, compared to 1.3 (SE, 0.4) with placebo. Likewise, those with ≥2 failures experienced a reduction of 3.1 days (SE, 0.7) and 3.8 days (SE, 0.8) with 120 mg and 240 mg, galcanezumab respectively, but only 0.5 days (SE, 0.6) with placebo.

Those with no prior failure also experienced reductions of 4.7 (SE, 0.2) and 4.5 (SE, 0.2) days with 120 mg and 240 mg galcanezumab, and although the placebo group reported a reduction of 3.0 days (SE, 0.2), the difference remained significant (P <.001).

At months 3 and 6, the estimated proportions of patients with ≥50% or ≥75% response were significantly greater with galcanezumab doses versus placebo (P < 0.01) for those with prior failure, as well as the subgroup with no prior failure (P < 0.001). Although, again, there was a larger placebo response in this subgroup.

Findings from this subgroup analysis are important given the recently published European Headache Federation and American Headache Society treatment guidelines that recommend initiating treatments targeting the CGRP pathway when multiple criteria are met, including the inability to tolerate or an inadequate response to at least two common oral preventives,” Goadsby and colleagues wrote, noting that the overall phase 3 trial populations showed efficacy in a broader population, but the need for cost-effective care, and the restricted access to the therapy, still remain.

“The study population herein consisted of patients who met the headache frequency and moderate disability thresholds described in the guidelines,” they wrote. “Therefore, these results will be valuable for prescribing physicians and healthcare policymakers who want to understand efficacy outcomes in the population with episodic migraine with at least 1 or at least 2 prior preventive treatment failures.”

REFERENCE

Ruff DD, Ford JH, Tockhorn-Heidenreich A, et al. Efficacy of galcanezumab in patients with episodic migraine and a history of preventive treatment failure: results from two global randomized clinical trials. Eur J Neurol. Published online November 6, 2019. doi: 0.1111/ene.14114.