Ubrogepant Safety Reaffirmed Over Long-Term Intermittent Use
New 52-week data from an extension study has suggested that recently FDA-approved ubrogepant (Ubrelvy; Allergan) is safe and tolerable, with minimal treatment-related adverse events with 2 doses assessed.
By: Matt Hoffman
Published: January 10, 2020
Jessica Ailani, MD, FAHS
New long-term extension study results suggest that using ubrogepant (Ubrelvy; Allergan) intermittently for the acute treatment of migraine is both safe and tolerable for patients, with little incidence of treatment-related adverse events (AEs) or need to discontinue medication accompanying its use.1
The 52-week, phase 3 data included 1230 participants receiving either 50 mg (n = 404) or 100 mg (n = 409) ubrogepant who administered 1 to 2 doses per migraine attack, or usual care (n = 417). All told, treatment-related AEs were reported by 10% (n = 42) and 11% (n = 43) of the low and high dose groups. Only 2% (n = 9) and 3% (n = 12) of those in the 50- and 100-mg groups, respectively, experienced serious AES. Discontinuation due to AEs occurred in 2.2% (n = 9) and 2.7% (n = 11) of the treatment groups.
Data were collected by a group of investigators, including Jessica Ailani, MD, FAHS, director, MedStar Georgetown Headache Center, and associate professor of neurology, MedStar Georgetown University Hospital. “Overall, data from this trial further support the safety profile of ubrogepant,” they wrote.
Ubrogepant was approved by the FDA for the acute treatment of migraine with or without aura in adults, making it the first-in-class oral calcitonin gene-related peptide (CGRP) antagonist for this indication, in December 2019. Its new drug application (NDA) was supported by data from the 2 pivotal studies—ACHIEVE I and II—as well as 2 additional safety studies. The results showed that both doses were effective, with patients reporting significant rates of pain freedom and freedom from most bothersome symptoms at 2 hours post-dose. It is contraindicated for co-administration with strong CYP3A4 inhibitors.2
Although this 52-week extension trial was not designed the compare AEs between the usual care and treatment groups, 65% (n = 271) of the usual care arm reported a treatment-related AE, though relatedness was not assessed. The most common were upper respiratory tract infection (n = 48; 11.5%), nasopharyngitis (n = 33; 7.9%), sinusitis (n = 25; 6.0%), urinary tract infection (n = 23, 5.5%), and influenza (n = 21, 5.0%).
With regard to hepatic safety, 2% (n = 16) of the 805 participants randomized to ubrogepant had increases in their ALT/AST ≥3× the upper limit of normal, compared to 1% (n = 4) of the 397 participants in the usual care arm. Investigators were unconcerned with the hepatic safety findings, with 13 of the 16 cases in the ubrogepant groups considered “unlikely related” to treatment. All told, 2 were judged “possibly related” and 1 “probably related.” Notably, there were confounding factors—increased alcohol and acetaminophen use, dilated bile duct, and prednisone use—in those 3 cases.
Ailani and colleagues wrote that “these findings, along with the observation that all aminotransferase elevations ≥3× ULN resolved in participants who continued ubrogepant dosing, indicate that there were no clinically meaningful hepatic safety signals for ubrogepant in this trial.” Additionally, these data help to confirm the findings of prior 12-week, high-frequency dosing hepatic safety trial in healthy volunteers.
“Long‐term intermittent use of ubrogepant 50 and 100 mg given as 1 or 2 doses per attack for the acute treatment of migraine was safe and well tolerated, as indicated by a low incidence of treatment‐related TEAEs and SAEs and discontinuations due to adverse events in this 1‐year trial,” Ailani and colleagues concluded.
Ailani spoke with NeurologyLive at the 2019 American Headache Society Annual Meeting, in Philadelphia, Pennsylvania, about this major unmet need in headache medicine—acute migraine treatments—and how ubrogepant may fill help to fill it. Watch her speak below.
1. Ailani J, Lipton RB, Hutchinson S, et al. Long‐Term Safety Evaluation of Ubrogepant for the Acute Treatment of Migraine: Phase 3, Randomized, 52‐Week Extension Trial. Headache. Published online January 8, 2020. doi: 10.1111/head.13682.
2. FDA approves new treatment for adults with migraine [press release]. Silver Springs, MD: FDA; Published December 23, 2019. fda.gov/news-events/press-announcements/fda-approves-new-treatment-adults-migraine. Accessed December 23, 2019.