Dr Jim MartinezJim Martinez, MD
Eli Lilly announced that the FDA granted priority review for its supplemental biologics application (sBLA) for galcanezumab (Emgality) injection for preventive treatment of episodic cluster headache in adults.

The sBLA is backed by data from a phase 3 trial (NCT02397473) that evaluated the safety and efficacy of 300-mg galcanezumab injection in 106 adults with episodic cluster headache. In September 2018, the FDA granted galcanezumab breakthrough designation therapy for episodic cluster headache.

“Episodic cluster headache is a severely painful headache disorder that can have a devastating impact on a person’s life,” Jim Martinez, MD, Senior Medical Director, Eli Lilly and Company, told NeurologyLive in an interview. “In part because episodic cluster headache can be difficult to study in clinical trials, there are few treatment options. In the U.S., there are currently no approved preventive treatments for episodic cluster headache. If approved, galcanezumab could provide a potential new treatment option for people living with episodic cluster headache, many of whom may have felt ignored and alone in their struggle.”

The phase 3 trial, one of the first placebo-controlled studies performed in cluster headache, demonstrated that across weeks 1 to 3 of the 2-month study period, monthly injections of 300-mg galcanezumab led to a statistically significant reduction in the frequency of cluster headache attacks compared to placebo (-8.7 reduction for galcanezumab versus -5.2 reduction for placebo; P = .036).

In regard to the secondary endpoint, at week 3, a statistically significant greater percentage of patients in the intervention arm (76%) achieved ≥50% reduction in weekly cluster headache attacks compared to placebo (57%) (P = .04).

Lilly is currently enrolling patients in a phase 3b study (NCT02797951) assessing the long-term safety and tolerability of galcanezumab in patients with episodic or chronic cluster headache. Patients that completed I5Q-MC-CGAL (NCT02397473) or I5Q-MC-CGAM (NCT02438826) phase 3 clinical trials, which evaluated a combined 343 patients and are the largest controlled preventive trials conducted in cluster headache, were potentially eligible to enroll. The study is evaluating 300 mg of galcanezumab administered subcutaneously up to once monthly. According to Martinez, if galcanezumab is approved, it will be the first preventive option approved for patients with episodic cluster headache in the United States.

The primary outcome measures of the long-term study are the number of participants with treatment emergent adverse events or serious adverse events from baseline through the end of the study, approximately 4 years, and the number of participants with suicidal ideation and behaviors collected by the Columbia-Suicide Severity Rating Scale from baseline through the end of the study. The second outcome measure includes the number of participants with treatment emergent anti-galcanezumab antibodies from baseline through the end of the study. The estimated completion date is August 2020.

“Cluster headache is a severely disabling and excruciating painful neurological disorder,” Gudarz Davar, MD, vice president, neurology development, Lilly Bio-Medicines, said in a statement.1 “Few treatment options are available, and only a limited body of research from rigorous clinical trials exists. We are pleased the FDA has granted priority review for our sBLA, acknowledging the need for new treatments for this devasting disease and bringing us closer to potentially offering a preventive treatment option for these patients.”

In September 2018, 120-mg injection of galcanezumab was approved for the preventive treatment of migraine in adults. Lilly is currently recruiting for phase 3 studies evaluating galcanezumab for prevention of migraine in children and adolescents ages 6­–17.
REFERENCE
1. Lilly Receives FDA Priority Review Designation for Emgality® (
galcanezumab-gnlm) Injection for the Preventive Treatment of Episodic Cluster Headache in Adults [news release]. Indianapolis: Eli Lilly and Company; March 5, 2019. https://investor.lilly.com/news-releases/news-release-details/lilly-receives-fda-priority-review-designation-emgalityr. Accessed March 5, 2019.