Regulatory Decision Summary for Elyxyb

The purpose of this New Drug Submission was to obtain market authorization, pursuant to section C.08.004 of the Food and Drug Regulations, for Elyxyb, filed by Scilex Pharmaceuticals Inc.

This submission was filed for Elyxyb (celecoxib), 25 milligrams per millilitre, oral solution, for the following indication: acute treatment of migraine with or without aura in adults.

Upon review of the submitted data package, Health Canada authorized Elyxyb, as filed.

The sponsor consented to information sharing between Health Canada and health technology assessment organizations as part of an aligned review pathway.

Two Phase 3 randomized, placebo-controlled, single attack, multicenter clinical trials were filed in this New Drug Submission to support the approval of Elyxyb (celecoxib oral solution) for the acute treatment of migraine with or without aura in adult patients.

Efficacy

The design of both studies was identical. The co-primary endpoints were the proportion of patients achieving freedom from pain and the absence of their most bothersome symptom (MBS) (nausea, photophobia or phonophobia) at 2 hours post-dose. Study 007 included 280 patients that received placebo and 283 patients that received Elyxyb. The Elyxyb group demonstrated statistically significant and clinically meaningful pain freedom and MBS freedom at 2 hours post-dose (co-primary efficacy endpoints) compared with the placebo group (pain freedom: 35.6% Elyxyb vs. 21.7% placebo, p less than 0.001; MBS freedom: 57.8% Elyxyb vs. 44.8% placebo, p = 0.007). Study 006 included 264 patients that received placebo and 280 patients that received Elyxyb. In Study 006, the co-primary endpoint of pain freedom at 2 hours was not statistically significant (32.9% Elyxyb vs. 25.8% placebo, p = 0.075), due to a pronounced placebo effect. However, the effect of Elyxyb on MBS freedom was significant and clinically meaningful compared to placebo (58.9% Elyxyb vs. 45.0% placebo, p = 0.003).

Safety

The safety profile of celecoxib is well characterized with over 20 years of use at higher doses than Elyxyb for the relief of symptoms of chronic conditions such as osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, as well as for the short-term management of moderate to severe acute pain in adults such as musculoskeletal or soft tissue trauma, including sprains, postoperative orthopedics, and pain following dental extraction. The safety of Elyxyb was supported by four Phase 1, one Phase 2, and two Phase 3 trials in which 941 participants received at least one dose of Elyxyb. There were no new or unexpected adverse events reported for Elyxyb treated patients in the clinical trials. The most commonly reported adverse events were dysgeusia (taste aversion) (3.0% Elyxyb, 1.2% placebo) and nausea (2.4% Elyxyb, 1.9% placebo). Most adverse events were mild or moderate and of low incidence, however, it should be noted that due to the study design, patients only received one dose per treatment period, limiting the power to detect less common adverse events. Given the known safety profile for celecoxib, the lower recommended dose of Elyxyb (120 milligrams [mg]) compared to other marketed celecoxib formulations (200 mg to 400 mg daily), and the recommended dosing instructions for Elyxyb, the absence of long-term safety data for this indication is considered acceptable. As Elyxyb is indicated to treat intermittent migraine attacks, the safety and efficacy of a second dose of Elyxyb following the first dose, or of multiple doses within a one-month period, were not studied. This was reflected in the Elyxyb Product Monograph which specifies that Elyxyb should only be used for the fewest number of days per month, based on individual therapeutic needs. In addition, the Elyxyb Product Monograph contains all of the safety information related to celecoxib and the class labelling for nonsteroidal anti-inflammatory drugs.

Overall, the benefit-harm-uncertainty profile for Elyxyb (celecoxib oral solution, 25 milligrams per millilitre), when used as recommended for acute treatment of migraine with or without aura in adults, is favourable. A Notice of Compliance was recommended.

Comparative bioavailability data demonstrated that a high-fat, high-calorie meal did not have a significant impact on the exposure of celecoxib in the commercial formulation of Elyxyb.

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

A Risk Management Plan for Elyxyb was reviewed by Health Canada and considered acceptable. The final labelling and Product Monograph were also considered acceptable.

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