Quarterly Infusions of Eptinezumab Highly Effective for Migraine Prevention in PROMISE 2

Richard B. Lipton, MD, Department of Neurology, Albert Einstein College of Medicine

Richard B. Lipton, MD

The intravenous quarterly CGRP inhibitor eptinezumab significantly reduced monthly migraine days (MMD) compared with placebo for patients with chronic migraine, according to findings from the 6-month phase III PROMISE 2 trial presented at the 60th Annual American Headache Society (AHS) Scientific Meeting.

In PROMISE 2, there was a reduction of -8.2 monthly migraine days with eptinezumab from baseline versus -5.6 with placebo (P <.0001). Following 2 quarterly infusions of eptinezumab at 300 mg, 21% of patients experienced a 100% reduction in MDDs. Just 9% of patients in the placebo group experienced this milestone.

“The efficacy data following two quarterly infusions from the PROMISE 2 trial demonstrate eptinezumab’s potential to offer both rapid and sustained suppression of migraine that is further improved for patients whose quality of life is severely impacted by this condition,” lead investigator Richard Lipton, MD, director of the Montefiore Headache Center, Albert Einstein College of Medicine, said in a statement. “My patients could potentially see great benefit from a treatment that can provide the level of efficacy seen with eptinezumab in the clinical studies.”

Additionally, after 2 quarterly infusions, 64% of patients had a ≥50% reduction in migraine days with eptinezumab compared with 44% with placebo. Forty-three percent had a reduction of ≥75% with eptinezumab compared with 24% for placebo.

Alder Biopharmaceuticals, the company developing eptinezumab, announced in January 2018 that the study had met its primary endpoint. Filing of a biologics license application (BLA) is anticipated for eptinezumab in the first quarter of 2019, the company said during a conference call in May.

"Our primary goal is the submission of a high-quality BLA that will meet the U.S. Food and Drug Administration’s requirements for approval and ensure eptinezumab’s successful commercial launch," Paul B. Cleveland, interim president and chief operations officer at Alder, said during the call. "As we committed, we have completed an internal review of all activities related to our BLA and have concluded that we can achieve a high-quality BLA submission in the first quarter of 2019."

In the phase III trial, 1072 patients with chronic migraines were randomized to receive either eptinezumab (300 mg or 100 mg) every 12 weeks or matched placebo. Eligible patients had experienced at least 15 headache days per month—with more than half meeting criteria for migraine. Researchers investigated for primary endpoint of mean change from baseline in monthly migraine days over the 12-week period.

Secondary endpoints included proportion of patients experiencing migraine on the day following treatment administration and reduction of migraine prevalence days 1-28; reduction of at least 50%, 75%, and 100% from baseline in mean monthly migraine days; change in baseline in mean monthly acute migraine therapy days; and reductions from baseline in the Headache Impact Test (HIT-6) impact scores, as reported by patients.

There were no new safety reports seen with the second quarterly infusion, and adverse event (AE) rates among patients administered eptinezumab were similar to those administered placebo. Among the most commonly reported AEs were nasopharyngitis (7.4%), urinary tract infection (2.8%), and nausea (2.5%).

“These data further add to the significant body of clinical evidence supporting eptinezumab’s encouraging clinical profile and reinforce our belief in the value it may provide to patients, if approved” Robert Azelby, chief executive officer of Alder, said in a statement. “The robust efficacy shown over the two quarterly infusions of eptinezumab in chronic migraine patients continues to support eptinezumab’s potential as an important treatment option for patients living with this debilitating condition.”

Eptinezumab, the only drug among the anti-CGRP class to be administered in quarterly infusions, is currently only an investigational monoclonal antibody developed by Alder for migraine prevention. Whether it is eventually approved for marketing in a field of great demand—at least 36 million Americans suffer from migraines&mdash;may hinge on the results of long-term, global trials such as PROMISE 2.