Eptinezumab
Unlike other anti-CGRP antibodies, eptinezumab is administered intravenously, once every 3 months, rather than by subcutaneous injection. This IgG1 anti-CGRP monoclonal antibody was engineered for reduced immune activation and a 30-day half-life. It’s onset of action is extremely rapid, with 100% of the agent being bioavailable within a few hours after administration.
The positive 12-week outcomes of the phase 3 randomized, double-blind, placebo-controlled PROMISE-2 trial of eptinezumab for prophylaxis against chronic migraine have previously been presented, as have the 1-year results in episodic migraine patients in PROMISE-1.
Dr. Roger K. Cady
Of those on the higher dose of eptinezumab, 33% had at least a 75% reduction in monthly migraine days from baseline, a figure that climbed to 43% after the second infusion; and of those who received eptinezumab at the 300-mg dose, 61% experienced a 50% or greater reduction in monthly migraine days from baseline during weeks 1-12, as did 64% during weeks 13-24 following a second infusion.
A key secondary endpoint in PROMISE-2 was the proportion of patients having a migraine on any given day. During the 28-day baseline period, that figure was 58%. But the day after the first infusion that proportion dropped to 28% in both the eptinezumab 100- and 300-mg groups, and that rate held through the next 12 weeks. In contrast, roughly 45% of placebo-treated controls had a migraine on any given day during the 12 weeks.
“The key thing is on the day following infusion you have established pretty much the full preventive value of eptinezumab, and it is maintained stable all the way through 12 weeks,” according to Dr. Cady, vice president of neurology at Alder BioPharmaceuticals, which is developing the biologic.
When an audience member remarked on the placebo response rates in the CRGP inhibitor studies and indeed in clinical trials in migraine generally, Dr. Cady responded with one of the meeting’s more memorable comments: “If placebo brought you to the dance, you’re still at the party.”
Dr. Winner reported serving as a consultant to Alder BioPharmaceuticals, which sponsored the HALO trials and is developing eptinezumab, as well as to numerous other pharmaceutical companies. Similarly, Dr. Goadsby, Dr. Ailani, and Dr. Silberstein are consultants to many companies, including Teva Pharmaceuticals, which is developing fremanezumab.