Regulatory Decision Summary for Ubrelvy

This New Drug Submission - New Active Substance (NDS-NAS) was filed to obtain market authorization for Ubrelvy (ubrogepant tablets) as a new active substance for the acute treatment of migraine with or without aura in adults.

This New Drug Submission- New Active Substance (NDS-NAS) sought an indication for Ubrelvy (ubrogepant tablets) for the acute treatment of migraine with or without aura in adults. Ubrogepant is part of a new class of drugs, called gepants, which are small molecule calcitonin gene-related peptide (CGRP) receptor antagonists. Ubrelvy was the first gepant approved by the United States Food and Drug Administration (FDA) on December 23, 2019, providing some degree of post-market experience. The recommended dosage of oral Ubrelvy is 50 milligrams (mg) or 100 mg taken as needed, without regard to food. A second dose may be administered at least 2 hours after the initial dose if needed, with a maximum dose in a 24-hour period of 200 mg.

The primary support for the indication was provided by two pivotal, randomized, placebo-controlled, single attack, safety and efficacy studies MD-01 (N = 1,415) and MD-02 (N = 1,355). In both studies, the 50 mg and 100 mg doses of Ubrelvy effectively provided freedom from migraine pain at 2 hours post-dose, as well as freedom from the most bothersome migraine-associated symptom (MBS), one of nausea, vomiting, photophobia, or phonophobia, at 2 hours post-dose and demonstrated statistically significant superiority over placebo on both co-primary endpoints. By contrast, the 25 mg dose demonstrated statistically significant superiority to placebo for pain-freedom at 2 hours, but not MBS-freedom at 2 hours. These are both well-validated and clinically meaningful migraine endpoints. There were no significant differences between the 50 mg and 100 mg doses, in terms of efficacy on these endpoints. While the data supported the efficacy of an optional second dose, study design flaws compromised the validity of those assessments, leaving the value of the optional second dose uncertain. Overall, efficacy was notably modest, relative to other anti-migraine medication, with response rates ranging from 19-21% and absolute treatment effect ranging from 7-9% for pain freedom at 2 hours and 10-12% for MBS-freedom at 2 hours.

Ubrelvy demonstrated a favourable safety profile. Safety was informed primarily by the two pivotal trials, as well as a long-term extension trial (MD-04) involving repeat dosing for up to one year. Ubrelvy was generally safe and well-tolerated. The most commonly reported adverse events were nausea, somnolence, and dry mouth. Most adverse events were mild or moderate and of low incidence. None of the clinical studies, including a dedicated hepatic safety study, discovered any indication of hepatotoxicity. Unlike triptans, ubrogepant is not a potent vasoconstrictor and safety studies found no increase in cardiovascular risk with Ubrelvy. A dedicated QT study found no significant QT prolongation with Ubrelvy. However, safety on the face of pre-existing cardiovascular conditions was not fully addressed, requiring ongoing pharmacovigilance.

Some uncertainty remains, regarding the safety of Ubrelvy use in geriatric patients, and pregnant or breast-feeding women. The safety of concomitant use of Ubrelvy with other gepants also remains unclear. However, these issues have been thoroughly addressed, through labelling and ongoing pharmacovigilance activities.

While the efficacy of Ubrelvy was relatively modest, it has a favourable safety profile and may represent an option to current available treatments (e.g., triptans) that may be unsuitable for patients who either do not respond well or are precluded from taking them due to contraindications or other safety issues.

Based on the safety and efficacy data currently available to Health Canada, the Benefit-Harm-Uncertainty of Ubrelvy (ubrogepant tablets) in the acute treatment of migraine attacks with or without aura in adults is considered favourable.

For further details about Ubrelvy, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.