FDA Accepts Galcanezumab Application for Migraine Prevention

Wei-Li Shao, vice president, US Lilly Neurosciences

Wei-Li Shao

The FDA has accepted a biologics license application (BLA) for galcanezumab as a prophylactic treatment for migraines, according to Eli Lilly and Company, the developer of the CGRP inhibitor.

The BLA included data from 3 phase III studies, namely the EVOLVE-1, EVOLVE-2, and REGAIN trials that evaluated the safety and efficacy of subcutaneous injections of galcanezumab at 120 mg or 240 mg once-monthly, following a 240-mg starting dose. In the trials, which evaluated galcanezumab in 2,901 patients, those treated with the monoclonal antibody experienced a statistically greater decrease in the average number of monthly migraine days compared with the placebo.

Under the Prescription Drug User Fee Act, the FDA is likely to decide on the application by September 2018.

"Across our phase III studies of galcanezumab, patients experienced a statistically significantly greater decrease in the average number of monthly migraine headache days compared to placebo, which translates to more migraine-free days for these patients," said Wei-Li Shao, vice president, US Lilly Neurosciences. "This is significant for patients who have not yet tried, or found, an effective treatment, and we are thrilled to bring a new era of innovative migraine therapies to market."

In both the EVOLVE-1 and EVOLVE-2 studies, patients with episodic migraine treated with galcanezumab at 120 mg and 240 mg doses experienced a significant decrease in the average number of monthly migraine days versus those treated with the placebo throughout the 6-month treatment period. Significant improvements were observed at each month, starting at 1 month of treatment.

In EVOLVE-1, a significant percentage of patients treated with both doses achieved at least a 50%, 75% and 100% reduction in the number of migraine days compared with placebo throughout the treatment period: patients that experienced at least a 50% reduction: 62.3% for the 120-mg dose and 60.9% for the 240-mg dose versus 38.6% for placebo; patients that experienced at least a 75% reduction: 38.8% for the 120-mg dose and 38.5% for the 240-mg dose versus 19.3% for placebo; and patients that experienced a 100% reduction: 15.6% for the 120-mg dose and 14.6% for the 240-mg dose versus 6.2% for placebo.

In EVOLVE-2, a significant percentage of patients also treated with both doses achieved at least a 50%, 75% and 100% reduction in the number of migraine headache days compared to placebo throughout the treatment period: patients that experienced at least a 50% reduction: 59.3% for the 120-mg dose and 56.5% for the 240-mg dose versus 36% for placebo; patients that experienced at least a 75% reduction: 33.5% for the 120-mg dose and 34.3% for the 240-mg dose versus 17.8% for placebo; and patients that experienced a 100% reduction: 11.5% for the 120-mg dose and 13.8% for the 240-mg dose versus 5.7% for placebo.

Patients treated with galcanezumab in both of the EVOLVE studies experienced a greater reduction of monthly migraine headaches with acute medication use compared to those treated with placebo.

An improvement was also demonstrated in physical function compared to placebo, as measured by both the Role Function-Restrictive (RF-R) domain score of the Migraine-Specific Quality of Life Questionnaire (MSQ) and the Patient Global Impression of Severity (PGI-S) rating after multiplicity adjustment.

Throughout a 3-month treatment period, patients with chronic migraine in the REGAIN study treated with galcanezumab 120 mg and 240 mg doses experienced a statistically greater decrease in the average number of monthly migraine headache days versus placebo.

A greater percentage of patients also achieved at least a 50% reduction in the number of migraine headache days versus placebo throughout the treatment period (27.6% for the 120-mg dose and 27.5% for the 240-mg dose versus 15.4% for placebo).

Compared with placebo, patients treated with the 240-mg dose of galcanezumab achieved at least a 75% reduction in the number of migraine headache days (8.8% versus 4.5% for placebo) after multiplicity adjustment, and achieved a greater reduction in the number of monthly migraine headache days with acute medication use (an average of 4.3 days compared to 2.2 days for placebo).

Patients treated with 240 mg saw a significant improvement in physical function, as measured by the RF-R domain score of the MSQ and PGI-S rating after multiplicity adjustment.

“For many people, the impact of migraine can be all-encompassing — a person may miss work, family activities or social engagements," Shao added. "Of the approximately 40% of all patients with migraine who are eligible for preventive therapy, only 13% are currently taking preventive medications. As such, millions of patients suffering from migraine are losing at least 1 month per year to migraine."

Galcanezumab was further evaluated in REGAIN for an additional 9 months of an open-label extension phase following the 3-month phase.

The monoclonal antibody is specifically designed to bind to and inhibit the activity of calcitonin gene-related peptide and is under evaluation for the prevention of migraine and cluster headache.