Galcanezumab Meets Primary Endpoint in Episodic Cluster Headache Study

James Martinez, MD

Eli Lilly and Company’s galcanezumab reached the primary endpoint in an episodic cluster headache trial, achieving statistically significant differences in the reduction of weekly cluster headache attacks compared to placebo across weeks 1 to 3 of the 2-month treatment period.

The drug also met its secondary endpoint, with a statistically significantly greater percentage of treated patients reaching at least a 50% reduction in weekly cluster headache attacks compared to placebo.

"Cluster headache can be difficult to evaluate in clinical studies, which has contributed to few available treatment options for cluster headache, often considered the most severe pain one can experience," said Christi Shaw, president of Lilly Bio-Medicines in a statement.

James Martinez, MD, Lilly medical fellow and study author, elaborated further, saying that patients with this condition experience headaches that are “excruciatingly severe.” He added that patients “get them nearly every day, sometimes multiple times per day over a period of weeks or months.”

The terrible pain is one reason Martinez shared about why clinical trials have been so challenging to complete.

“Imagine getting these excruciating headaches multiple times per day for weeks or even longer and then being willing to participate in a trial with an unproven treatment,” Martinez told MD Magazine.

He added that the intermittent nature of the episodic cluster headache type can also be a challenge in testing efficacy.

The 2-month trial included 106 patients with episodic cluster headache with an average of 17.5 cluster headache attacks per week at baseline. Patients were randomized to receive galcanezumab (300 mg once-monthly) or placebo.

Unlike acute headache treatments, which are taken at the onset of each headache, researchers administered galcanezumab subcutaneously on a monthly basis during the trial.

“[Preventative treatments] try to reduce the overall number of headaches. They might try to get someone from having 3 attacks per day to just 1 per day,” said Martinez. “We’ve studied galcanezumab as a preventative.”

The patients treated with galcanezumab experienced statistically significant differences in the reduction of weekly cluster headache attacks compared to patients treated with placebo during the first 3 weeks of the study (-8.7 for galcanezumab compared to -5.2 for placebo, p=0.036).

"The positive results in episodic cluster headache are truly a landmark moment—both for people living with cluster headache and for our researchers at Lilly, many of whom have spent more than two decades researching and developing innovative, non-opioid treatment options for diseases like migraine and cluster headache," said Shaw.

The manufacturer, Eli Lilly, previously conducted a phase 3 trial of galcanezumab for patients with chronic cluster headache that did not meet its primary endpoint. However, previous trials of the drug for patients with other conditions returned positive results. EVOLVE-1, EVOLVE-2, and REGAIN were successful phase 3 studies that evaluated the safety and efficacy of galcanezumab for migraine prevention.

Late last year, the US Food and Drug Administration (FDA) accepted a Biologics License Application for galcanezumab for the prevention of migraine in adults based on the EVOLVE-1, EVOLVE-2, and REGAIN trials. Lilly expects a decision from the FDA in the third quarter of 2018.

“The results from the episodic cluster headache study were really promising. It is a difficult headache disorder to study, so we were pleased to conduct the study and demonstrate efficacy,” said Martinez. Given the positive results, Martinez said that the company will begin dialogue with regulators at the FDA.