CGRP Monoclonal Antibodies May Be Beneficial for Migraine Prevention
Galcanezumab
The efficacy, tolerability, and safety of galcanezumab, an investigational drug for the treatment of episodic migraine, was assessed in a six-month phase III study called EVOLVE-2. In this study, patients with episodic migraine experienced four to 14 migraine headache days per month with or without aura. “Our patient population had a mean age of about 40, and most [participants] were Caucasian women,” said Robert Conley, MD, Distinguished Lilly Scholar of Neuroscience at Eli Lilly and Company (the developer of galcanezumab) in Indianapolis.
“Half of our subjects were from North America, a quarter from Europe, and a quarter from the rest of the world.” Subjects had a 20-year migraine history on average and a mean of nine headache days per month at baseline, he noted. “In addition, two-thirds had been on prior preventive treatment, and they had relatively severe levels of disease.”
After screening 1,700 patients for the study, Dr. Conley and colleagues randomized 914 patients 1:1:2 to subcutaneous injection of galcanezumab (120 mg/month), galcanezumab (240 mg/month), or placebo. “There was about an 87% completion rate for the galcanezumab groups and an 83% completion rate in the placebo group. The higher number of dropouts in the placebo group was due to lack of efficacy,” said Dr. Conley. The primary end point was change from baseline in MMD at the end of six months. Secondary end points were percentages of patients with 50%, 75%, and 100% response rates; reduction in MMD requiring acute migraine medication; change in function score on the Migraine-Specific Quality of Life Questionnaire (MSQ); and change in the Patient Global Impression of Severity (PGI-S) rating.
After adjusting for multiplicity, the investigators found statistically significant differences between placebo and the galcanezumab arms in the primary end point. Mean reductions in headache days were 4.29 in the 120-mg group and 4.18 in the 240-mg group. Patients in the placebo group experienced a reduction of 2.28 days. “We looked at the early effects of treatment and found statistically significant improvements within a few days of injection that persisted over time,” Dr. Conley said.
In addition, statistically significant differences between galcanezumab and placebo were observed for all secondary end points. “In the 120-mg and 240-mg treatment groups, 59.3% and 56.5%, respectively, had at least a 50% reduction in monthly headache days, which was significantly different from placebo, but not different from each other,” said Dr. Conley. “We also saw that approximately one-third of patients in the galcanezumab arms experienced 75% response rates, which is double that seen in the placebo group. The 100% response rate was 11.5% to 13.8% in the treated groups—again, not a significant difference between them, but significantly different from placebo.” The change in the MSQ function score and the PGI-S rating averaged for months 4, 5, and 6 were significantly improved in the galcanezumab arms, compared with the placebo arm.
For most of the safety parameters, there were no significant differences between either dose of galcanezumab and placebo. However, the rates of injection-site reactions and pruritus were significantly higher for both drug doses, compared with placebo. Injection-site erythema was significantly higher in the 240-mg dose only.
Fremanezumab
“The phase III trial for fremanezumab in chronic migraine investigated a flexible dose for a quarterly and a monthly regimen,” said Ernesto Aycardi, MD, Vice President and Therapeutic Area Head for Migraine and Headache at Teva Pharmaceuticals
The primary end point of this multicenter trial was the mean change from baseline in monthly days of headache of at least moderate severity. The four main secondary end points were the proportion of patients with at least a 50% reduction in headache days, mean change in the number of days using acute headache medication at the end of the 12-week period of the trial, mean change from baseline in the days of at least moderate severity in the first four weeks of the trial, and change in disability scale (HIT-6) score from baseline. In this trial, patients treated with fremanezumab experienced significant improvement, compared with placebo on all primary and secondary end points for both monthly and quarterly dosing regimens.
“The average age of the study population was 41, with an average history of migraine of about 20 years,” Dr. Aycardi said. “All demographic characteristics, including weight, height, and ethnicity, were well balanced between the groups.”
Patients on the monthly regimen had a mean reduction of 4.6 headache days of at least moderate severity, and patients on the quarterly regimen had a reduction of 4.3 headache days of at least moderate severity, which was significantly different from the placebo group (2.5 headache days). Researchers also observed significant differences for each of the four secondary end points in favor of the monthly and quarterly regimens.
“Fremanezumab was well tolerated, compared with placebo,” Dr. Aycardi said. “The most commonly reported adverse event in the study was injection-site pain, with similar rates in the placebo and active groups.”
Dr. Aycardi highlighted how phase II results validated that target in chronic migraine. “With these phase III results, this is confirmed, bringing hope for patients with this disabling condition.”
—Adriene Marshall
