Regulatory Decision Summary for Nurtec ODT

This New Drug Submission-New Active Substance was filed to obtain market authorization for Nurtec ODT (rimegepant orally disintegrating tablet) for acute treatment of migraine with or without aura and for the preventative treatment (prophylaxis) of episodic migraine in adults. After review, only the indication for acute treatment of migraine with or without aura was granted.

Rimegepant, the active ingredient of Nurtec ODT (orally disintegrating tablet) is a new active substance. It is classified as a calcitonin-gene-related peptide (CGRP) inhibitor.

Support for market authorization of Nurtec ODT for acute treatment of migraine was provided in three randomized, double-blind, placebo-controlled, single-dose, Phase 3 safety and efficacy studies (BHV3000-301, -302, and -303). A total of 3,551 participants were randomized 1:1 to placebo, 75 milligram (mg) Nurtec ODT or a bioequivalent rimegepant tablet formulation. The 75 mg dose of rimegepant (ODT or tablet) was significantly more effective than placebo for the proportion of patients achieving the co-primary endpoints of pain freedom at 2 hours postdose (19.2%, 19.6%, and 21.2% with rimegepant vs. 14.2%, 12.0%, and 10.9% with placebo in Study 301, 302, and 303, respectively) and absence of most bothersome symptom (patient-specified choice of photophobia, phonophobia, or nausea) associated with migraine at 2 hours postdose (36.6%, 37.6%, and 35.1% with rimegepant vs. 27.7%, 25.2, and 26.8% with placebo in Study 301, 302, and 303 respectively). Secondary endpoints were generally supportive, including the key secondary endpoint of pain relief at 2 hours postdose.

Across the Phase 3 studies, the most common treatment-emergent adverse events (TEAEs) in Nurtec ODT treatment arms of the three controlled studies were nausea, vomiting, dry mouth, and somnolence. The only on-treatment adverse event (AE) occurring in at least 1% of participants in either overall treatment group was nausea, and no AEs were reported at an incidence greater than 2%.

Long-term safety of Nurtec ODT was assessed in one open-label trial (N = 1,514), and the safety profile was similar to that observed in the controlled studies. The most common TEAEs were dizziness, nausea, constipation, and somnolence. There were no new safety signals or unexpected AEs in the open-label trial.

A dedicated thorough QT study was performed. In the double-blind, randomized, placebo- and positive-controlled, crossover electrocardiogram assessment study in healthy subjects (N = 38), single 75 mg (therapeutic) and 300 mg (supratherapeutic) doses of Nurtec ODT did not show any noteworthy pharmacodynamic effects on the QTc interval, the QRS duration, the PR interval, or heart rate.

Dedicated Phase 1 studies investigating Nurtec ODT pharmacokinetics in elderly participants, those with renal or hepatic impairment, and lactating individuals, as well as studies investigating potential interactions between Nurtec ODT and other drugs that may be administered concomitantly were conducted. Risk mitigation measures have been implemented based on the results of these studies.

Notable uncertainties included a limited number of elderly participants across studies (N = 131), use of Nurtec ODT in pregnant individuals, participants with end-stage renal disease or undergoing dialysis, have been addressed in the approved Product Monograph (PM).

Health Canada identified issues with the data available for the prophylaxis indication that prevented its approvability as part of the current submission. As these concerns could not be resolved with the available data and analysis, the sponsor agreed to no longer pursue this indication within this submission.

Upon review, the Risk Management Plan was considered acceptable with some revisions.

The chemistry and manufacturing information submitted for Nurtec ODT demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

The potential effect of decreased rimegepant exposure after administration of Nurtec ODT with food is unknown as the proposed product was administered without regard for food in the clinical safety and efficacy studies. Nurtec ODT is proposed to be taken with or without food.

Following review and requested revisions, the final labelling and PM were considered to be acceptable.

Overall the benefit-harm-uncertainty profile is favourable for Nurtec ODT therapy for the acute treatment of migraine in adults when the product is used as described in the approved PM. Therefore, a Notice of Compliance (NOC) pursuant to section C.08.004 of the Food and Drug Regulations was recommended.

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