The anti-CGRP treatment continues reducing migraine days a year after patients received infusions.
Stephen D. Silberstein, MD
New 1-year efficacy data from PROMISE 1, a phase III clinical trial of eptinezumab in patients with episodic migraine, has revealed that patients reported further reductions in monthly migraine days after their third and fourth quarterly infusions of the trial drug.
Presented at the American Headache Society’s 60th Annual Scientific Meeting, in San Francisco, California, the results showed that 1 year after the third and fourth quarterly infusions, those administered the 300-mg dose of the calcitonin gene-related peptide (CGRP) inhibitor reported reductions of 5.2 monthly migraine days, compared to 4.0 for patients in the placebo group. The trial therapy’s efficacy was not statistically compared against placebo for this timepoint.
“These data are very encouraging, especially for the majority of my patients who have struggled to find relief from traditional treatment options and have discontinued use either due to lack of efficacy or side effects,” Stephen D. Silberstein, MD, a professor of neurology and the director of the Jefferson Headache Center, at Thomas Jefferson University, said in a statement.1 “I look forward to the promise of a potential treatment that not only shows a strong efficacy profile but also demonstrates that the benefit may even further improve after each dose.”
Following their first infusion, epitnezumab also lowered monthly migraine days by 4.3 days (baseline, 8.0) for patients treated with the 300-mg dose. Comparatively, those treated with placebo experienced reductions of 3.2 days (P = .0001). Additionally, approximately 31% of patients treated with the CGRP inhibitor achieved a 100% reduction of migraine days from baseline on average per month, compared to about 21% for patients administered placebo.
Altogether, the double-blind, placebo-controlled trial randomized 888 qualified patients to receive either eptinezumab (300 mg, 100 mg, or 30 mg) or placebo infusion, once weekly for 12 weeks. All patients had previously experienced at ≥14 headache days per month, with ≥4 headaches meeting the International Classification of Headache Disorders 2nd Edition (ICD-II) criteria for migraine.
“The encouraging and consistent results from the PROMISE 1 trial showing that eptinezumab provided both immediate and long-term efficacy over a period of a year, reinforce our confidence in eptinezumab’s potential to be a meaningful new treatment option for migraine prevention,” said Robert Azelby, MBA, the chief executive officer of Alder, in a statement. "These data further validate the significance of our clinical program and underscore Alder’s commitment to transform the treatment paradigm for migraine prevention for patients whose quality of life is severely impacted by this debilitating disease.”
The safety profile remained consistent with previous findings, as no new safety findings were observed with the third and fourth quarterly infusions. The most commonly reported adverse events (AEs), happening at a rate of ≥2.0% across all eptinezumab treatment groups, and greater than that of placebo were upper respiratory tract infection (10.5%), nasopharyngitis (6.8%), fatigue (3.2%), diarrhea (2.3%) and oropharyngeal pain (2.0%).
Previously, the therapy reported an average reduction of ≥50% monthly migraine days from baseline in 70.7% of patients, compared to just 58.7% for patients given placebo through months 6 to 12.2 That was an 8.9% improvement from mean reductions reported during the first 2 quarterly doses of therapy. Another 51.5% of eptinezumab patients reached a mean monthly migraine day reduction of ≥75% from baseline, while only 38.7% of patients given placebo reported that rate—a 12.8% improvement on the reduction rate reported by patients given therapy in the first 2 quarterly doses.
The therapy is also being investigated in the phase III PROMISE 2 trial. In January 2018, Alder Biopharmaceuticals, the developer, announced that the therapy also met all its key secondary endpoints in that study.3
1. Alder BioPharmaceuticals Presents New One-Year Data for Eptinezumab from PROMISE 1 Phase 3 Trial Demonstrating Long-Term Efficacy in
Migraine [press release]. Bothell, WA: Alder BioPharmaceuticals; June 29, 2018. globenewswire.com/news-release/2018/06/29/1531751/0/en/Alder-BioPharmaceuticals-Presents-New-One-Year-Data-for-Eptinezumab-from-PROMISE-1-Phase-3-Trial-Demonstrating-Long-Term-Efficacy-in-Episodic-Migraine.html. Accessed June 30, 2018.
2. Saper J, Lipton R, Kudrow D, et al. Primary Results of PROMISE-1 (Prevention Of
Safety and Efficacy—1) Trial: a Phase 3, Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of
for Prevention of Frequent Episodic Migraines. Neurology. 2018;90(15S):S20.001.
3. Alder announces
significantly reduces migraine risk meets primary and all key secondary endpoints in pivotal PROMISE 2 phase 3 trial for chronic migraine prevention [news release]. Bothell, WA: Alder BioPharmaceuticals Inc. January 8, 2018. globenewswire.com/news-release/2018/01/08/1284947/0/en/Alder-Announces-Eptinezumab-Significantly-Reduces-Migraine-Risk-Meets-Primary-and-All-Key-Secondary-Endpoints-in-Pivotal-PROMISE-2-Phase-3-Trial-for-Chronic-Migraine-Prevention.html. Accessed June 30, 2018.