Concomitant Atogepant and Ubrogepant for Acute and Preventive Migraine Demonstrates Safety

New data from the phase 4, 2-period, open-label TANDEM trial (NCT05264129) showed that treatment with atogepant (Qulipta; AbbVie) 60 mg once daily (QD) as a migraine preventive in combination with ubrogepant (Ubrelvy; AbbVie) 100 as needed (PRN) as an acute therapy was safe and well tolerated over a 12-week period.¹

Presented at the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18 in Denver, Colorado, the study featured 263 enrolled patients with migraine, with or without aura, who had less than 15 headache days/month. In the trial, participants were treated with atogepant 60 mg QD for 12 weeks for part 1, followed by ubrogepant 100 mg PRN added to atogepant for the treatment of breakthrough migraine attacks (up to 8/month). Period 2, which included 218 of the 262 treated patients, lasted 12 weeks as well, and allowed patients to use an optional second ubrogepant dose to rescue unresolved headaches within 2-24 hours post-dose.

Led by senior investigator Jessica Ailani, MD, director of the MedStar Georgetown Headache Center, the most common treatment-emergent adverse events (TEAEs) observed in safety populations 1 and 2 were COVID-19 (8.4%, 3.2%), fatigue (6.5%, 1.4%), nausea (6.1%, 0.9%), decreased appetite (5.7%, 0.9%), and constipation (5.3%, 0.9%). TEAEs were slightly more frequent in safety population 1 (49.6%) than 2 (43.1%). Overall, there was 1 serious TEAE in each period (period 1: ureterolithiasis; period 2: myelopathy) that were both considered unrelated to the study treatments.

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Patients were on ubrogepant for a mean number of 6.6 (SD, 5.03; min-max: 1-24) use days over 12 weeks of period 2 (n = 188). Overall, 9.9% of all participants discontinued any treatment because of TEAEs. Atogepant a calcitonin gene-related peptide (CGRP) antagonist approved for preventive migraine, and ubrogepant, a CGRP receptor antagonist approved for acute treatment, were deemed safe to use concomitantly by investigators.

A previous phase 1b study showed that the combination of approach of atogepant and ubrogepant at the highest FDA-approved dose strengths was safe for patients with migraine. At total of 31 patients were enrolled in March 2021, and 26 completed the study a few months later. The 5 patients who discontinued the study were either because they withdrew consent (n = 3), had an AE of rash (n = 1), or an AE of drug eruption (n = 1).

Led by Andrew Blumenfeld, MD, director of the Headache Center of Southern California, the trial’s primary objective was to assess pharmacokinetic (PK) interactions of the highest approved dose of each therapy, with ubrogepant administered on a fixed-dose schedule every 3 days. Atogepant, administered in 60 mg QD, had plasma concentrations that were similar upon concomitant administration with a single 100 mg dose of ubrogepant. All told, the point estimates for atogepant Cmax and area under the curve (AUC) were 104.09 (90% CI, 94.02-115.25) and 10.4.48 (90% CI, 97.59-111.86), respectively; thus, meeting the predefined DDI criteria of between 80% to 125% for no significant interaction.

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REFERENCES
1. Brand-Schieber E, Lipton R, Blumenfeld A, et al. Safety and tolerability of ubrogepant for the acute treatment of migraine in participants taking atogepant for the preventive treatment of episodic migraine: results from the TANDEM trial. Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO. POSTER 006390
2. Blumenfeld AM, Boinpally R, Ferreira RA, et al. Phase 1b, open-label, fixed-sequence, drug-drug interaction, safety, and tolerability study between atogepant and ubrogepant in participants with a history of migraine. Headache. Published online January 5, 2023. doi:10.1111/head.14433.