Consistent Effects for Galcanezumab in Cluster Headache

Erik Greb

June 24, 2020

Galcanezumab (Emgality, Eli Lilly and Co), the humanized monoclonal antibody that targets calcitonin gene–related peptide (CGRP), provides consistent improvements over time for patients with episodic cluster headache, new research suggests.

A post hoc analysis of patients from the phase 3 CGAL study who also entered the open-label CGAR extension study was conducted. Results showed that the majority of participants whose scores on the Patient Global Impression of Improvement (PGI-I) showed improvement 1 month after the initial dose of galcanezumab in the CGAL study also showed improvement after treatment for subsequent cluster bouts during the CGAR study.

"There was good agreement between PGI-I between the two [cluster headache] periods," note the investigators, led by Brian Plato, DO, neurologist at Norton Neuroscience Institute in Louisville, Kentucky.

The findings were presented at the American Headache Society (AHS) Annual Meeting 2020, which was conducted virtually this year because of the COVID-19 pandemic.

Two Cluster Periods

As reported by Medscape Medical News, galcanezumab was approved by the US Food and Drug Administration in 2019 for the treatment of episodic cluster headache in adults.

Attacks of recurrent, unilateral cluster headaches with cranial autonomic symptoms last for weeks or months and are followed by periods of remission.

Most studies of therapies for cluster headache examine only one cluster period. Few data about the consistency of treatment response throughout consecutive cluster periods are available, the investigators note.

The current analysis was undertaken to examine the consistency of galcanezumab's effect in episodic cluster headache during two cluster periods. Patients eligible for inclusion in the analysis had completed the double-blind phase of the CGAL study and had entered the open-label CGAR study.

CGAL was a phase 3, multicenter, randomized, double-blind study in which patients with episodic cluster headache were assigned to receive galcanezumab 300 mg per month or placebo.

Patients who completed the double-blind and washout phases of this study were eligible for enrollment into CGAR, a phase 3b, single-arm safety study. The investigators determined the dose of galcanezumab in accordance with each patient's symptoms and clinical response.

Response Agreement

In both studies, the PGI-I was administered 1 month after the initial dose of galcanezumab. Only patients who were in an active cluster bout upon entry into CGAR and who had valid PGI-I results 1 month after the first dose in CGAL and CGAR were included in the analysis.

PGI-I responses ranged from 1, signifying very much better, to 7, signifying very much worse. The investigators summarized the proportions of patients who reported each level of PGI-I score in CGAR and analyzed the results by dichotomizing PGI-I scores at both time points in two ways.

Fifty patients entered CGAR (78% men; mean age, 46.8 years). Of this group, Plato and colleagues included 39 in their analysis.

Of the 17 patients who had a PGI-I score of 1 or 2 in CGAL, 12 (70.6%) had a score in the same range in CGAR. All four participants who had a score of 3 or higher in CGAL had a score in the same range in CGAR.

Eighteen participants had a PGI-I score of 1, 2, or 3 in CGAL. Of this group, 15 patients (83.3%) had a score in the same range in CGAR. Of the three patients who had a score above 3 in CGAL, two (66.7%) had a score in the same range in CGAR.

The results indicate that most patients whose PGI-I score improved in one cluster bout, such as in CGAL, also improved in a subsequent bout, such as in CGAR, the investigators note.

"Encouraging" Results

Commenting on the study for Medscape Medical News, Brian E. McGeeney, MD, neurologist at the John R. Graham Headache Center, Brigham and Women's Faulkner Hospital, Boston, Massachusetts, noted that the PGI-I is an "easy-to-understand" outcome that has been widely used in headache medicine.

"Patient-assessed outcomes have become increasingly important and are an important complement to other outcomes," said McGeeney, who was not involved in the research.

However, a disadvantage is that "it is entirely subjective and may or may not reflect a change on other outcome measures that reflect the disorder itself," he said.

"It can be difficult to demonstrate how much usefulness a treatment has with the helpful but simple outcome measures that are seen in CGAL and CGAR," McGeeney added. "This is due to the nature of cluster headache and not to any methodological shortcomings of those studies."

He said this is a core problem in general with cluster headache studies, "of which there are very few."

In addition, CGAR only included episodic cluster headache, and the study period was relatively short; and CGAL only explored one cluster period per patient, McGeeney noted.

The current research attempts to provide insight that was previously unavailable, he said.

"Many headache medicine clinical trial results reflect only one episode, and in general, we infer repeated usefulness ― although it is not demonstrated in clinical trials," said McGeeney.

"In this recent presentation, the authors attempt to go further and demonstrate some consistency across multiple cluster periods. The results are encouraging and what one might expect," he said.

However, "the small numbers and ad hoc nature preclude much inference from this study alone."

Plato has received honoraria for speaking from Allergan, Amgen/Novartis, and Eli Lilly. He has also received research grants and support from Electrocore and Teva. McGeeney has consulted for Upsher-Smith and Theranica.

American Headache Society (AHS) Annual Meeting 2020: Abstract 838654, presented June 13, 2020.

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