Regulatory Decision Summary for Qulipta

This Supplemental New Drug Submission was filed to obtain market authorization for Qulipta (atogepant) for the prevention of chronic migraine (greater than or equal to 15 migraine days per month) in adults.

Qulipta (atogepant) is a Calcitonin gene-related peptide (CGRP) receptor antagonist that is currently authorized in Canada for the prevention of episodic migraine (less than 15 migraine days per month) in adults. The current Supplemental New Drug Submission was submitted to include an indication for the prevention of chronic migraine (greater than or equal to 15 migraine days per month) in adults.

The safety and efficacy was supported with a Phase III, placebo-controlled trial (Trial 303) in chronic migraine participants, who received either placebo (n = 259) or Qulipta (30 milligrams [mg] twice daily [BID] or 60 mg once daily [QD] [n = 518]) over a 12-week treatment period. Approximately 87% of participants in each treatment arm were female, with a mean age of 42 years (range: 18-74 years).

At baseline, participants experienced an average of 19 migraine days per month. Qulipta treated participants experienced an average of 2.1 fewer migraine days per month than the participants in the placebo group (p <0.001). In addition, 43% of Qulipta treated patients experienced greater than or equal to 50% reduction in monthly migraine days over the course of the study, compared to 26% of placebo treated participants (p <0.001). The majority of the secondary endpoints provided further support for the efficacy of Qulipta in the prophylaxis of chronic migraine.

The safety profile of Qulipta for prophylaxis of chronic migraine was similar to that for episodic migraine. The most common treatment-emergent adverse events (TEAEs) in Qulipta treated arms were nausea, constipation, decreased appetite, and dizziness. There were no new or unexpected adverse effects compared to the known safety profile of Qulipta.

Long-term safety of Qulipta was established in an open-label study (Trial 309) included and reviewed in the original New Drug Submission (control number 253186) which was conducted in participants with episodic migraine (n = 261) treated with Qulipta 60 mg QD for up to 40 weeks. The current submission included the interim results (104 weeks) from two open-label studies; Trial 312 which was conducted in participants with either episodic (n = 282) or chronic (n = 230) migraine, as well as Trial 306, which was conducted in Japanese participants. Overall, the results from Trial 312 and Trial 306 did not reveal any significant differences in safety compared to controlled studies in either episodic or chronic migraine. The most common reported adverse events included constipation, nausea, and decreased appetite. While similar events (for example nausea, constipation, increased transaminases) led to discontinuation in open-label studies, a slightly higher percentage of participants discontinued from study 312 due to TEAEs (4.9%) and study 306 (6%) compared to study 309 (3.2%).

The sponsor has committed to establishing a pregnancy registry for Canadian patients by the end of second quarter (Q2) of 2024. The Product Monograph will be updated accordingly at that time.

Overall, the benefit-harm-uncertainty profile was favourable for Qulipta (60 mg QD) for the approved indication when used under the conditions of use recommended in the approved Product Monograph. The indication was updated to be in line with other drug products for the same indication. Therefore, a Notice of Compliance (NOC) was recommended.

At this time, and based on the available information to Health Canada, the benefit-harm-uncertainty of Qulipta use in the prevention of both episodic and chronic migraine is favorable.

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