November 20, 2019
The novel oral calcitonin gene-related peptide (CGRP) receptor antagonist ubrogepant (Allergan) is safe and effective for treating acute migraine, final results from the phase 3 ACHIEVE II trial indicate.
They reinforce topline results presented in April 2018 at the annual meeting of the American Academy of Neurology and reported by Medscape Medical News at that time.
The new findings were published online November 19 in JAMA.
ACHIEVE II was a randomized, placebo-controlled trial that evaluated ubrogepant 50 mg and 25 mg for acute treatment of a migraine attack of moderate or severe pain intensity. Coprimary efficacy outcomes were freedom from pain and freedom from the most bothersome migraine-associated symptom 2 hours after dosing.
Among 1686 participants, 1465 received study treatment (safety population). Of these patients, 1355 (92.5%) were evaluable for efficacy.
Rates of freedom from pain at 2 hours were significantly greater with ubrogepant 50 mg (101 of 464 patients, 21.8%) and 25 mg (90 of 435, 20.7%) than with placebo (65 of 456, 14.3%).
The absolute difference for 50 mg vs placebo was 7.5% (95% confidence interval [CI], 2.6% – 12.5%; P = .01). The absolute difference for 25 mg vs placebo was 6.4% (95% CI, 1.5% – 11.5%; P = .03).
Rates of freedom from the most bothersome migraine-associated symptom at 2 hours were significantly greater with ubrogepant 50 mg (38.9%) but not 25 mg (34.1%) vs placebo (27.4%).
Additionally, ubrogepant 50 mg was statistically superior to placebo with respect to the absence of light sensitivity (43.8% for 50 mg and 35.5% for placebo) and sound sensitivity (54.1% for 50 mg and 46.3% for placebo).
Both the 50-mg and the 25-mg doses of ubrogepant were well tolerated, with an adverse event profile similar to placebo. The most common adverse reaction was nausea.
The US Food and Drug Administration is expected to act on the new drug application for ubrogepant in December, Allergan said in a news release announcing publication of the ACHIEVE II results.
"Migraine is the second leading cause of disability, and we need new acute treatments that are efficacious, safe, and tolerable," lead investigator Richard Lipton, MD, from Montefiore Headache Center, Albert Einstein College of Medicine, New York City, said in the release.
"Having ubrogepant as a potential new medication for the acute treatment of migraine will provide much-needed innovation for a disease that causes lost time for millions of people," he added.
ACHIEVE II was funded by Allergan. Lipton serves as consultant, advisory board member, or has received honoraria from Alder, Allergan, Amgen, Autonomic Technologies, Avanir, Boston Scientific, Dr Reddy's, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Novartis, Teva, and Vedanta and serves on the editorial boards of Neurology and Cephalalgia. The original article has a complete list of the author's relevant financial disclosures.