Phase III results have shown galcanezumab is efficacious for multiple headache conditions.
Robert Conley, MD
Galcanezumab, anti-calcitonin gene-related peptide (CGRP) medication, has been shown to significantly reduce headache days in patients with both migraine and cluster headache.
Phase III data presented at the 60th Annual Meeting of the American Headache Society (AHS) in San Francisco, California, detailed that the therapy reduced weekly cluster headache attacks in comparison with placebo in 1 study, as well as proved efficacious in comparison to placebo for patients who both did and did not fail ≥2 prior therapies.
In the episodic cluster headache trial, patients were treated with either 300-mg galcanezumab once monthly or placebo, with assessments across weeks 1 to 3. The trial therapy revealed a -8.7 reduction in weekly cluster headaches compared to -5.2 with placebo (P = .036). Of those receiving galcanezumab, 76% achieved a ≥50% reduction in weekly cluster headache attacks at week 3, compared to 57% with placebo (P = .04).
"Often confused with migraine, cluster headache is a neurological disease that has been characterized as 'beyond excruciating' by those who live with it," said Christi Shaw, MBA, president of Lilly Bio-Medicines, in a statement.1 "We are proud to present full results of this data, which represents potential hope for a resilient community of people struggling to prevent episodic cluster headache."
Additionally, on the Patient Global Impression of Improvement (PGI-I) scale, 73% of those treated with galcanezumab reported improvements by week 4, compared to 46% with placebo (P = .016).
The safety data for the therapy in episodic cluster headache was consistent with what has been observed in the examination of galcanezumab for migraine treatment. In total, 8% of those treated with the CGRP inhibitor discontinued treatment compared to 21% with placebo. Additionally, 4% of the intervention arm patients discontinued due to adverse events (AEs), while 2% of the placebo patients did. A lack of efficacy prompted withdrawal from the study in 2% of the treatment patients compared to 14% of those administered placebo (P = .036).
In subgroup analysis in patients with episodic and chronic migraine from a trio of trials—EVOLVE-1, EVOLVE-2, and REGAIN—the therapy was explored in 2 doses, 120 mg or 240 mg, for its impact on the mean change in the number of monthly migraine days and a ≥50% response in patients who both failed and did not fail ≥2 prior treatments. EVOLVE-1 and EVOLVE-2 explored the therapy for 6 months, while REGAIN assessed it for 3 months.
It was shown to significantly improve the overall mean reduction of monthly migraine headache days in both subgroups of patients (P <.001).2 For those who failed ≥2 prior therapies, the reduction in EVOLVE were -3.45 days for the 120-mg dose and -3.85 days for the 240-mg dose, compared to -0.81 days with placebo. In REGAIN, the reductions for that subgroup were -5.91 days with the 120-mg group and -3.30 days with the 240-mg group, compared to -1.44 with placebo. The 240-mg dose reduction in EVOLVE and the 120-mg dose reduction in REGAIN were significant in treatment-by-subgroup interaction.
For both subgroups in the EVOLVE studies and the REGAIN study, the mean percentage of patients achieving a ≥50% response was significantly higher compared to placebo.
The manufacturer, Eli Lilly, also announced that the FDA has conditionally accepted the therapy’s proposed brand name, Emgality. The therapy is set for review under a Prescription Drug User Fee Act (PDUFA) action date of September 11, 2018.
"People with migraine and cluster headache can miss out on significant moments in their lives—birthdays, anniversaries, business meetings—and there remains an unmet need for treatment options that can help patients achieve significant reductions in the overall frequency of migraine headaches and cluster headache attacks," said Robert Conley, MD, a Distinguished Lilly Scholar and Lilly global development leader for migraine therapeutics, in a statement.3 "The data presented at this year's meeting underscore Lilly's 50-year commitment to address the ongoing challenges in neurology, primary headache disorders and chronic and recurrent pain."
1. AHS 2018: Lilly Highlights Positive Phase 3 Results from the Largest Controlled Preventive Trial in Episodic Cluster Headache [press release]. Indianapolis,
Eli Lilly & Co; June 27, 2018. lilly.mediaroom.com/index.php?s=9042&item=137797. Accessed June 30, 2018.
2. Zhang Q, Ruff DD, Pearlman EM, Govindan S, Aurora SK. Efficacy of
in Patients Who Failed to Respond to Preventives Previously: Results from EVOLVE-1, EVOLVE-2 and REGAIN Studies. Neurology. 2018;90(15 Suppl)
3. Lilly to Present Phase 3 Data at AHS 2018 Highlighting Innovative Potential Treatments for
and Cluster Headache [press release]. Indianapolis,
Eli Lilly & Co; June 25, 2018. prnewswire.com/news-releases/lilly-to-present-phase-3-data-at-ahs-2018-highlighting-innovative-potential-treatments-for-migraine-and-cluster-headache-300671337.html. Accessed June 30, 2018.