Migraine Treatment Galcanezumab Meets Primary Endpoint in Late-Stage Studies

FDA submission expected later this year

Galcanezumab (Eli Lilly), an investigational treatment for the prevention of episodic and chronic migraine, has met the primary endpoint in three phase 3 trials (EVOLVE-1, EVOLVE-2, and REGAIN), demonstrating statistically significant reductions in the number of monthly migraine headache days compared with placebo at both studied doses. Based on these results, Lilly plans to submit a biologics license application to the FDA for galcanezumab in the second half of 2017.

Galcanezumab is a monoclonal antibody designed to bind to and inhibit the activity of calcitonin gene-related peptide (CGRP), which is believed to play a role in migraine and cluster headache. Galcanezumab is an investigational once-monthly, self-administered subcutaneous injection under evaluation for the prevention of migraine and cluster headache.

The EVOLVE-1 and EVOLVE-2 trials were six-month, randomized, double-blind, placebo-controlled global studies evaluating the safety and efficacy of two doses of galcanezumab administered subcutaneously (120 mg or 240 mg once monthly, following a 240-mg starting dose) compared with placebo in patients with episodic migraine. To be eligible for these trials, patients must have experienced between four and 14 migraine headache days per month. Patients who participated in these trials had an average of 9.1 migraine headache days per month at baseline. The primary endpoint was the mean change from baseline in monthly migraine headache days over the six-month, double-blind treatment phase.

In both studies, during the six-month treatment period, patients with episodic migraine treated with galcanezumab 120 mg or 240 mg experienced a significantly greater reduction in the average number of monthly migraine headache days compared with patients given placebo. In EVOLVE-1, the patients achieved an average reduction of 4.7 days for the 120-mg dose and 4.6 days for the 240-mg compared with an average reduction of 2.8 days for placebo (P < 0.001 for both dosing groups). In EVOLVE-2, the patients achieved an average reduction of 4.3 days for the 120-mg dose and 4.2 days for the 240-mg compared with an average reduction of 2.3 days for placebo (P < 0.001 for both dosing groups).

In addition, patients treated with galcanezumab experienced statistically significant improvements compared with placebo on several prespecified secondary endpoints, including response rates and measures of daily activities.

The REGAIN trial was a three-month, randomized, double-blind, placebo-controlled, global study evaluating the safety and efficacy of two doses of galcanezumab administered subcutaneously (120 mg or 240 mg once monthly, following a 240-mg starting dose) compared with placebo in patients with chronic migraine. To be eligible for the trial, patients must have experienced at least 15 headache days per month, of which at least eight met the criteria for migraine. Patients who participated in the trial had an average of 19.4 migraine headache days per month at baseline. The study’s primary endpoint was the mean change from baseline in monthly migraine headache days during the three-month, double-blind treatment phase. Galcanezumab was further evaluated for an additional nine months of an open-label extension phase after the three-month, double-blind treatment phase.

During the three-month treatment period, patients with chronic migraine treated with galcanezumab 120 mg or 240 mg experienced a significantly greater reduction in the average number of monthly migraine headache days compared with patients treated with placebo (an average reduction of 4.8 days for 120 mg and 4.6 days for 240 mg compared with 2.7 days for placebo [P < 0.001 for both dosing groups]).

In addition, patients treated with galcanezumab experienced statistically significant improvements compared with placebo on several prespecified secondary endpoints, including response rates and measures of daily activities.

Migraine is a disabling neurological disease characterized by recurrent episodes of severe headache and is often accompanied by other symptoms, including nausea, vomiting, sensitivity to light and sound, and changes in vision. More than 38 million Americans have migraine, with three times more women affected than men. The Migraine Research Foundation has estimated that the annual costs of health care and lost productivity associated with migraine may be as high as $36 billion in the United States

Source: Eli Lilly; May 12, 2017.