Dr Stephen D. SilbersteinStephen D. Silberstein, MD
More than two-thirds of patients treated with intravenous infusions of the CGRP inhibitor eptinezumab had an average 50% reduction in migraines, according to 12-month data from the phase III PROMISE 1 trial presented at the AAN Annual Meeting.

For the long-term analysis, patients with episodic migraines were dosed once every 3 months. Through months 6 to 12, 70.7% of patients treated with eptinezumab reported an average reduction of 50% or greater of monthly migraine days from baseline compared with just 58.7% for patients given placebo. The reduction was an 8.9% improvement from mean reductions reported during the first 2 quarterly doses of therapy.

Based on an earlier assessment of the data, Alder BioPharmaceuticals submitted a Biologics License Application to the FDA for eptinezumab. Under the Prescription Drug User Fee Act (PDUFA), the FDA will decide on the application in September 2018.

“I am very excited to see the encouraging results in migraine prevention shown in the PROMISE 1 long-term data,” Stephen D. Silberstein, MD, professor of Neurology and Director of the Jefferson Headache Center, Thomas Jefferson University, said in a statement. “I see a significant need for my patients for a treatment that provides rapid, effective, well-tolerated and long-term results and I’m looking forward to the FDA’s review of these data.”

The original double-blind, placebo-controlled global 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 least 14 headache days per month, with 4 of such headaches meeting the criteria for migraine.

Primary endpoint for the trial was mean change from baseline in monthly migraine days over the treatment period. Results presented at the AAN meeting focused on the therapy’s extended results through month 12.

At the long-term follow-up, 51.5% of patients treated with eptinezumab reached a mean monthly migraine day reduction of 75% or greater from baseline. Just 38.7% of patients given placebo reported that rate. This represented a 12.8% improvement with extended treatment compared with reports from the first 2 quarterly doses.

The most commonly reported adverse events in all eptinezumab treatment groups were upper respiratory infection (10.5%), nasopharyngitis (6.8%), and sinusitis (3.6%).

Eptinezumab is also backed by another phase III trial (PROMISE 2), in which 1072 patients with chronic migraines were randomized to receive either eptinezumab (300 mg or 100 mg) or placebo, which Alder initially reported was positive in January 2018. This trial also met secondary endpoints of reduction in migraine prevalence day 1 and days 1 to 28 post infusion.

In PROMISE 2, there was a reduction of -8.2 monthly migraine days with eptinezumab versus -5.6 placebo (P <.0001). This represented a 51% reduction in migraines days. Additionally, 61% of patients had a ≥50% reduction in migraine days with eptinezumab compared with 39% with placebo. A third of patients (33%) had a reduction of ≥75% with eptinezumab compared with 15% for placebo.

“These clinically significant data clearly demonstrate that eptinezumab delivered by infusion provided rapid, effective and sustained migraine relief,” Randall C. Schatzman, PhD, president and chief executive officer of Alder. “If approved, eptinezumab has the potential to advance the treatment paradigm in chronic migraine prevention and be a meaningful treatment option for millions of the most severely impacted patients.”