LOS ANGELES—Among patients with chronic migraine, IV infusion of eptinezumab significantly reduces the average number of migraine days per month, compared with placebo, according to phase III trial data presented at the 70th Annual Meeting of the American Academy of Neurology. In addition, one-year data from a trial of eptinezumab in patients with episodic migraine suggest that treatment response may improve with subsequent infusions, researchers said.
Eptinezumab (formerly known as ALD403) is a humanized monoclonal antibody that inhibits calcitonin gene-related peptide (CGRP). It is designed to be administered quarterly via IV infusion. Eptinezumab previously was found to be effective and well tolerated in phase II studies in episodic and chronic migraine and in a phase III trial in episodic migraine. Alder BioPharmaceuticals, based in Bothell, Washington, is developing the therapy.
Treatment-emergent adverse events in phase III studies were similar for eptinezumab and placebo, and the safety profile was consistent with that in prior studies, researchers said.
The PROMISE Clinical Trial Program
The Prevention of Migraine via Intravenous ALD403 Safety and Efficacy (PROMISE) clinical trial program includes phase III, randomized, double-blind, placebo-controlled trials of eptinezumab for chronic migraine prevention (PROMISE-2) and episodic migraine prevention (PROMISE-1).
In the PROMISE-2 trial, 1,072 patients were randomized to receive eptinezumab (300 mg), eptinezumab (100 mg), or placebo administered by IV infusion once every 12 weeks. Eligible patients had at least 15 headache days per month, of which at least eight met criteria for migraine. The primary end point was the mean change from baseline in monthly migraine days over the 12-week treatment period. Secondary end points included reduction in migraine prevalence on Day 1 and the proportion of patients with reductions of at least 50% and 75%.
In the PROMISE-1 trial, 888 patients were randomized to receive eptinezumab (300 mg), eptinezumab (100 mg), eptinezumab (30 mg), or placebo administered by IV infusion once every 12 weeks. Eligible patients had 14 or fewer headache days per month, of which at least four met the criteria for migraine. The primary end point was the mean change from baseline in monthly migraine days over the 12-week treatment period.
PROMISE-2
Patients in PROMISE-2 had an average of about 20 headache days per month, including 16 migraine days, at baseline, said Richard B. Lipton, MD, Edwin S. Lowe Chair in Neurology at Albert Einstein College of Medicine in New York. Patients’ mean age was about 40, mean BMI was 26, and about 88% were female.
Richard B. Lipton, MD
Patients had had migraine for about 18 years on average, and mean duration of chronic migraine was about 12 years.
During the 12 weeks after treatment, the mean change from baseline in monthly migraine days was –7.7 for patients who received the 100-mg dose of eptinezumab and –8.2 for patients who received the 300-mg dose of eptinezumab, compared with –5.6 for patients who received placebo. The difference was statistically significant for both active treatment groups versus placebo.
Secondary end points significantly favored eptinezumab. The percentage of patients with at least a 75% reduction in migraine days was 15.0% for placebo, 26.7% for the 100-mg dose of eptinezumab, and 33.1% for the 300-mg dose of eptinezumab. The percentage of patients with at least a 50% reduction in migraine days was 39.3% for placebo, 57.6% for the 100-mg dose of eptinezumab, and 61.4% for the 300-mg dose of eptinezumab.
On Day 1 post infusion, the percentage of patients with migraine decreased by 51% and 52% in the 100-mg and 300-mg treatment arms, respectively, compared with a decrease of 27% in the placebo arm.
Adverse event rates among eptinezumab-treated subjects were similar to those in placebo-treated subjects. The most commonly reported adverse events for eptinezumab were nasopharyngitis (6.3%), upper respiratory infection (4.0%), and nausea (3.4%).
Treatment-emergent adverse events occurred in approximately 40% of all treatment arms (39% in the placebo group, 38% in the 100-mg group, and 44% in the 300-mg group). Serious adverse events were rare, occurred in approximately equal rates in all treatment arms, and were considered unrelated to study drug.
PROMISE-1
Patients in PROMISE-1 had a mean age of about 40, and about 85% were female. They had about 8.5 migraine days per month on average, said Stephen D. Silberstein, MD, Professor of Neurology and Director of the Jefferson Headache Center at Thomas Jefferson University in Philadelphia.
During Weeks 1–12, mean change in monthly migraine days was significantly greater among patients who received eptinezumab (–4.0 with the 30-mg dose, –3.9 with the 100-mg dose, and –4.3 with the 300-mg dose), compared with patients who received placebo (–3.2).
One-year data indicated that the percentage of participants in the trial with 75% and 50% reductions in migraine increased over time. “With each subsequent infusion, there seems to be a cumulative increase in response,” Dr. Silberstein said. At the end of the trial, the proportion of patients in the 300-mg dose group with at least a 75% reduction in migraine days was 52%, whereas the proportion at Month 3 was 37%. The long-term results are encouraging, said Dr. Silberstein.
In PROMISE-1, the most commonly reported adverse events among treated patients were upper respiratory infection (10.3%), nasopharyngitis (6.6%), and sinusitis (3.6%).
—Jake Remaly