The review period for the oral CGRP receptor antagonist has been set at 10 months, with a Prescription Drug User Fee Act action date in the fourth quarter of 2019.
C. David Nicholson, PhD
Allergan has announced that the FDA accepted its New Drug Application (NDA) for ubrogepant, an investigational acute treatment for migraine in adult patients.1
The NDA is supported by data from the 2 pivotal studies conducted by Allergan—ACHIEVE I and II—as well as 2 additional safety studies—UBR-MD-04 and 3110-105-002. The review period has been set at 10 months, with a Prescription Drug User Fee Act (PDUFA) action date in the fourth quarter of 2019.
"Following the acceptance and expected review of this NDA, we anticipate ubrogepant to be the first approved oral CGRP receptor antagonist for the acute treatment of migraine and may be used in conjunction with other available migraine treatments," said C. David Nicholson, PhD, the Chief Research and Development Officer at Allergan, in a statement. "As a leader in chronic migraine research for more than 20 years, Allergan looks to provide options for patients who need new acute and preventative treatments for migraine.”
The therapy has shown success in both of its phase 3 assessments. In ACHIEVE I, ubrogepant was administered to treat a single migraine attack in comparison with placebo (n = 456) at doses of 50 mg (n = 423) and 100 mg (n = 448) in 1327 patients. The study met its primary end points, with both doses showing a larger, statistically significant percentage of patients achieving pain freedom at 2 hours after the initial dose (50 mg, P = .0023; 100 mg, P = .0003) as well as a statistically significant greater percentage of patients achieving absence of the most bothersome migraine-associated symptom at 2 hours after the initial dose (50 mg vs placebo, p=0.0023, 100 mg vs placebo, p=0.0023) compared to placebo.2
In ACHIEVE II, the therapy was examined in 1686 patients randomized 1:1:1 to 25-mg (n = 435) or 50-mg (n = 464) ubrogepant, or placebo (n = 456). In total, 20.7% and 21.8% of patients in the 25-mg and 50-mg groups, respectively, were pain-free at 2 hours post-initial dose compared to 14.3% of placebo patients (25 mg, P = .0285; 50 mg, P = .0129). For the co-primary end point of absence from the most bothersome symptom, including photophobia, phonophobia, and nausea, the calcitonin gene-related peptide (CGRP) antagonist-treated groups experienced freedom at rates of 34.1% and 38.9%, respectively, compared to 27.4% with placebo (25 mg, P = .0711; 50 mg, P = .0129).3
In study UBR-MD-04, a phase 3, multicenter, randomized, 52-week open-label extension trial in which adults with migraine were randomized 1:1:1 to usual care, ubrogepant 50 mg, or ubrogepant 100 mg to assess long-term safety and tolerability, the treatment was well-tolerated over 1 year. The 3 most frequently reported adverse events (AEs) were nasopharyngitis, upper respiratory tract infection and sinusitis.
Study 3110-105-002 was a phase 1, multicenter, double-blind, parallel-group trial which evaluated the safety and tolerability of ubrogepant 100 mg—specifically, the hepatic safety in healthy participants administered high-frequency intermittent dosing (2 days of ubrogepant 100 mg followed by 2 days of placebo for 8 consecutive weeks). The 100-mg dose was well-tolerated and was not associated with persistent increases in ALT/AST compared to placebo, supporting liver safety.
"Despite its prevalence and burden, migraine remains an undertreated disease, with many patients continuing to seek additional treatment options from their physicians," said Jessica Ailani, MD, a neurologist and the director of the Medstar Georgetown Headache Center. "If approved, ubrogepant, the first innovation in the acute treatment of migraine in over 25 years, will be used across the entire spectrum of the disease [from episodic to chronic] helping patients achieve relief in the moments when they most demand it."
“In addition to ubrogepant, we are continuing to advance the phase 3 clinical program for atogepant, the company's second orally-administered investigational CGRP receptor antagonist specifically for migraine prevention," Nicholson added.
1. Allergan Announces FDA Acceptance of New Drug Application for Ubrogepant for the Acute Treatment of Migraine [press release]. Dublin, Ireland: Allergan. Published March 11, 2019. allergan.com/news/news/thomson-reuters/allergan-announces-fda-acceptance-of-new-drug-appl. Accessed March 11, 2019.
2. Allergan Announces Positive Top Line Phase 3 Results for Ubrogepant - an Oral CGRP Receptor Antagonist for the Acute Treatment of Migraine [press release]. Dublin, Ireland: Allergan. Published February 6, 2018. allergan.com/news/news/thomson-reuters/allergan-announces-positive-top-line-phase-3-resul. Accessed March 11, 2019.
3. Allergan Announces Second Positive Phase 3 Clinical Trial for Ubrogepant -- an Oral CGRP Receptor Antagonist for the Acute Treatment of Migraine [press release]. Dublin, Ireland: Allergan. Published April 27, 2018. allergan.com/news/news/thomson-reuters/allergan-announces-second-positive-phase-3-clinica. Accessed March 11, 2019.