Eptinezumab (Vyepti) reduced the number of monthly migraine days for people who had two to four previous migraine prevention treatment failures, the phase IIIb DELIVER trial showed.
Changes in mean monthly migraine days were -4.8 for eptinezumab 100 mg, -5.3 eptinezumab for 300 mg, and -2.1 for placebo from baseline to weeks 1 to 12, reported Messoud Ashina, PhD, DMSc, of the University of Copenhagen in Denmark and co-authors.
The difference from placebo was significant for both eptinezumab 100 mg (-2.7, 95% CI -3.4 to -2.0, P<0.0001) and 300 mg (-3.2, 95% CI -3.9 to -2.5, P<0.0001).
“Overall, our results show that eptinezumab is efficacious compared with placebo for the preventive treatment of migraine in adults with migraine and two to four previous preventive treatment failures, with an acceptable safety and tolerability profile similar to that previously reported for eptinezumab,” Ashina and colleagues wrote in The Lancet Neurology.
Eptinezumab, a monoclonal antibody that targets calcitonin gene-related peptide (CGRP), has shown migraine preventive effects starting the day following infusion in phase III trials, but had not been studied in people with previous treatment failures. Four anti-CGRP monoclonal antibodies — eptinezumab, erenumab (Aimovig), galcanezumab (Emgality), and fremanezumab (Ajovy) — are approved in the U.S. for migraine prevention.
The accumulating evidence of efficacy of anti-CGRP monoclonal antibodies should encourage clinicians to embrace the new treatments in clinical practice and focus on emerging unmet needs, wrote Raffaele Ornello, MD, and Simona Sacco, MD, both of the University of L’Aquila in Italy, in an accompanying editorial.
“Ideally, physicians should individualize treatments according to the needs of each patient; for some patients, the first treatment option, might be an anti-CGRP monoclonal antibody,” Ornello and Sacco observed.
Eptinezumab is administered intravenously and the other three anti-CGRP drugs are administered subcutaneously, the editorialists noted. “Notably, the reduction in migraine days was appreciable from the first day of treatment” in the DELIVER trial, they pointed out.
DELIVER had a 24-week double-blind, placebo-controlled period followed by a 48-week dose-blinded extension. Adults with episodic or chronic migraine who had at least four monthly migraine days and documented evidence of two to four previous preventive treatment failures within the past 10 years were recruited in Europe and the U.S.
Patients were randomly assigned 1:1:1 to eptinezumab 100 mg, eptinezumab 300 mg, or placebo. The primary efficacy endpoint was the change from baseline in mean monthly migraine days in weeks 1 to 12; data were captured in a daily electronic diary. People with previous anti-CGRP therapy failures were excluded, as were those with clinically significant cardiovascular disease or confounding pain syndromes.
Between June 2020 and October 2021, 299 people received eptinezumab 100 mg, 294 received eptinezumab 300 mg, and 298 received placebo. A total of 865 people completed the placebo-controlled period.
Participants were predominantly female and white with a mean age of 43.8. Just under half (46%) had chronic migraine, and 42% had high-frequency episodic migraine (8-14 monthly migraine days) at baseline. Most participants (62%) had two prior treatment failures; about a third (31%) had three.
Treatment-emergent adverse events occurred in 42% of people in the eptinezumab 100 mg group, 41% of the eptinezumab 300 mg group, and 40% of the placebo group. The most common treatment-emergent adverse event was COVID-19, which affected 7% in the eptinezumab 100 mg group, 6% in the eptinezumab 300 mg group, and 5% in the placebo group.
Serious adverse events were uncommon and included anaphylactic reaction (two people in the eptinezumab 300 mg group) and COVID-19 (one in each of the eptinezumab dosing groups).
“Results of this study add to the growing body of evidence supporting the use of anti-CGRP monoclonal antibodies in this population of patients with migraine with treatment failures with traditional oral preventive treatments,” Ashina and colleagues wrote.
“The study population reflects the eligibility requirements for reimbursed CGRP-targeting treatments in some countries and reflects many patients with migraine encountered in specialized outpatient headache clinics,” the researchers added. “Eptinezumab provides a viable treatment option for these patients who have not benefited from or tolerated traditional migraine preventive therapies.”
The findings might not apply to the general migraine population or to other migraine patients with multiple treatment failures, given regional differences in the availability and recommended order of using preventive migraine medications, the investigators acknowledged.
This study was funded by H Lundbeck.
Researchers reported multiple relationships with industry, academic institutions, non-profit agencies, professional societies, and publishers.
Ornello reported speaker fees from Eli Lilly, Novartis, and Teva, support for attending meetings or travel from Novartis and Teva; advisory board fees from Eli Lilly, and non-financial support from Allergan and Novartis. Sacco reported consultant, advisory board, or speaker fees from Abbott, Allergan, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi-Sankyo, Eli Lilly, Medscape, Medtronic, Novartis, StarMed, Teva, and Uriach.