‘PROMISE’-ing results against migraine

BOTHELL, Wash.—Alder BioPharmaceuticals Inc., a biopharmaceutical company focused on developing novel therapeutic antibodies for the treatment of migraine, announced in late June new one-year efficacy data from the PROMISE 1 Phase 3 clinical trial in patients with episodic migraine. The data demonstrate that patients experienced even further reductions in monthly migraine days (MMDs) following the third and fourth quarterly infusions of eptinezumab, Alder’s lead investigational product candidate for migraine prevention targeting calcitonin gene-related peptide (CGRP). Results were presented at the 60th American Headache Society Annual Scientific Meeting in San Francisco.

Eptinezumab is an investigational monoclonal antibody discovered and developed by Alder BioPharmaceuticals for migraine prevention. It is a potent and selective anti-CGRP mAb administered by quarterly infusion for migraine prevention, delivering 100-percent bioavailability to immediately inhibit CGRP. Eptinezumab has been studied in several global, randomized, double-blind, placebo-controlled studies to assess its safety and efficacy in migraine prevention.

“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, CEO of Alder. “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 PROMISE 1 (PRevention Of Migraine via Intravenous eptinezumab Safety and Efficacy 1) trial was a Phase 3 randomized, double-blind placebo-controlled global trial evaluating the safety and efficacy of eptinezumab for episodic migraine prevention. In the study, patients were randomized and 888 received eptinezumab (300 mg, 100 mg or 30 mg), administered by infusion once every 12 weeks. To be eligible for the trial, patients must have experienced at most 14 headache days per month, of which at least four met the criteria for migraine.

The primary endpoint was the mean change from baseline in monthly migraine days over the 12 week treatment period. In June 2017, Alder announced that eptinezumab met the primary endpoint—and also key secondary endpoints—in PROMISE 1 with very high statistical significance.

Following the first quarterly infusion, patients treated with 300 mg experienced 4.3 fewer MMDs from a baseline of 8 MMDs, compared to 3.2 fewer MMDs for placebo from baseline. At one year after the third and fourth quarterly infusions, patients treated with 300 mg experienced further gains in efficacy, with a reduction of 5.2 fewer MMDs compared to 4.0 fewer MMDs for placebo-treated patients. (Eptinezumab’s efficacy was not statistically compared against placebo.)

Approximately 31 percent of patients achieved, on average per month, 100-percent reduction of migraine days from baseline compared to approximately 21 percent for placebo. This means that almost one-third of patients, on average, experienced monthly migraine freedom when treated with 300 mg of eptinezumab.

The observed safety profile for PROMISE 1 to date is consistent with previously reported eptinezumab studies. The most commonly reported adverse events occurring at an incidence of 2 percent or greater across all eptinezumab treatment groups and greater than placebo were: upper respiratory tract infection (10.5 percent), nasopharyngitis (6.8 percent), fatigue (3.2 percent), diarrhea (2.3 percent) and oropharyngeal pain (2.0 percent). There were no new safety findings observed with the third and fourth quarterly infusions.

Migraine is a highly symptomatic and debilitating disease affecting a large patient population. Preventative treatments, if effective, may take weeks to months to achieve meaningful clinical benefits, and fail to meet the needs of most patients. Furthermore, up to 80 percent of patients discontinue use within six months to a year due to lack of efficacy and/or side effects.

“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,” said Dr. Stephen D. Silberstein, a professor of neurology and director of the Jefferson Headache Center, Thomas Jefferson University. “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.”