No differences were observed in the magnitude of ubrogepant treatment effect between defined triptan subgroups.
Susan Hutchinson, MD
The oral small molecule CGRP receptor antagonist ubrogepant led to freedom from migraine pain, resolution of the most bothersome migraine-associated symptom (MBS), and pain relief for patients for whom triptans were ineffective, according to a pooled analysis of the phase III ACHIEVE I and II studies presented at the 2019 American Headache Society (AHS) Annual Meeting, July 11-14, 2019, in Philadelphia, Pennsylvania.
"Despite whether the candidate was triptan-naive, triptan-effective, or triptan-ineffective, there is a benefit to using ubrogepant. It was effective across the board compared with placebo," Susan Hutchinson, MD, Orange County Migraine & Headache Center. "I certainly think that we're starting to see that this could have clinical relevance for those of us in practice."
Data from the ACHIEVE I and II studies were included in a new drug application for ubrogepant, which was accepted for review by the FDA in March 2019. Data from the UBR-MD-04 and 3110-105-002 trials were also submitted as part of the application. The FDA is scheduled to make a decision on the application by the end of the year.
The ACHIEVE I study included 1672 patients and explored ubrogepant at 50 mg and 100 mg doses compared with matched placebo. The ACHIEVE II study enrolled 1686 patients and examined 25 mg and 50 mg doses of ubrogepant compared with placebo. Data from both studies for those receiving the 50 mg dose (n = 887) and matched placebo (n = 912) were pooled for the AHS analysis.
Baseline patient characteristics were similar between groups. Across both trials, 57% to 64% of patients had moderate headache pain and 36% to 43% had severe headache pain. The most commonly reported MBS was photophobia (55% to 59% of patients). Triptans were deemed ineffective for a quarter of patients, with the most common cause being insufficient efficacy (81%). Thirty-seven percent of patients were triptan-naive and triptans were effective for 37% of those in the ubrogepant arm.
In the triptan-ineffective group, freedom from pain 2 hours following the initial dose was achieved for 16% of patients in the ubrogepant group compared with 8% in the placebo group (odds ratio [OR], 2.16; 95% CI, 1.19-3.95). This magnitude of benefit was similar to the triptan-naive and triptan-effective groups.
In the group of patients for whom triptans were effective, 20% were free of pain at 2 hours with ubrogepant compared with 11% with placebo (OR, 2.03; 95% CI, 1.32-3.11). In the triptan-naive group, 24% and 18% were free from pain at 2 hours in the ubrogepant and placebo groups, respectively (OR, 1.37; 95% CI, 0.94-2.01).
In the triptan-ineffective group, absence of MBS at 2 hours was achieved for 36% of those treated with ubrogepant and for 23% of those in the placebo arm (OR, 1.76; 95% CI, 1.16-2.68). In the treatment-naive and triptan-effective groups, respectively, MBS was resolved for 41% and 39% with ubrogepant compared with 31% and 27% for placebo. The odds ratio was 1.50 in the triptan-naive group (95% CI, 1.09-2.08) and was 1.81 for the triptan-effective group (95% CI, 1.31-2.52).
Pain relief at 2 hours was achieved by 55% of those treated with ubrogepant compared with 43% with placebo in the triptan-ineffective arm (OR, 1.64; 95% CI, 1.12-2.40). In the triptan-naive group, ubrogepant relieved pain for 66% of patients compared with 58% for placebo (OR, 1.39; 95% CI, 1.01-1.93). In the triptan-effective group, 62% had pain relief at 2 hours compared with 44% with placebo (OR, 2.19; 95% CI, 1.60-2.99).
"No differences were observed in the magnitude of treatment effect between the defined triptan subgroups," said Hutchinson.
Treatment-emergent adverse events (AEs) occurred in 11.5% of patients in the placebo group and for 11.2% of those in the ubrogepant group. The rate of treatment-related AEs was the same in both groups (7.2%). There were no serious AEs and the most common treatment-emergent AEs were nausea, somnolence, and dry mouth.
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Blumenfeld AM, Goadsby PJ, Dodick DW, et al. Ubrogepant is effective for the acute treatment of migraine in patients for whom triptans are ineffective. Presented at: American Headache Society 2019, Philadelphia, PA, July 11-14, 2019.