Efficacy, tolerability, and safety of ubrogepant confirmed

Ubrogepant is a calcitonin gene-related peptide receptor antagonist in development for acute migraine. In the multicentre, double-blind, phase 3 ACHIEVE II study, ubrogepant 50 mg resulted in a significantly higher rate of freedom from headache and absence of the most bothersome migraine-associated symptom after 2 hours [1].

A total of 1,686 adults with a history of migraine were randomised to placebo, ubrogepant 25 mg, or 50 mg. Patients had 60 days to treat a single migraine attack of moderate or severe pain intensity. Significantly greater proportions of ubrogepant-treated patients achieved 2-hour pain freedom. In the placebo, 25 mg, and 50 mg groups these rates were 14.3, 20.7% (adjusted P=0.029), and 21.8% (adjusted P=0.013). Compared with placebo, the 2-hour absence of most bothersome symptom was also significantly higher in the 50 mg group (adjusted P=0.013). All secondary efficacy endpoints (except absence of nausea after 2 hours) met statistical significance versus placebo in the 50 mg group. Ubrogepant was well-tolerated and had a safety profile similar to placebo.

Results from the ACHIEVE I and ACHIEVE II study were also combined in an analysis of the impact of ubrogepant on patient-reported functional disability, satisfaction with study medication, and headache relief [2]. In both placebo-controlled trials, a higher proportion of ubrogepant-treated patients reported normal function (single-item functional disability scale) and overall satisfaction with treatment, and indicated their migraine was much better. The results of these patient-centred outcomes were found to be clinically meaningful by the authors and reinforce the potential benefits of ubrogepant in the acute treatment of migraine.

In a 1-year safety analysis of ubrogepant, asymptomatic elevations of liver enzymes were reported that resolved with continued dosing. Bilirubin was not elevated [3]. A separate study found no significantly prolonged QT intervals at therapeutic and supratherapeutic doses of up to 400 mg, which were well-tolerated in healthy adults [4].

1. Trugman JM, et al. AAN 2019, S38.008.
2. Viswanathan HN, et al. AAN 2019, P2.10-012.
3. Ailani J, et al. AAN 2019; abstract P2.10-009.
4. Jakate A, et al. AAN 2019; abstract P2.10-003.



Posted on 30 July 201915 March 2021