Regulatory Decision Summary for Suvexx

Suvexx is a combination product consisting of sumatriptan succinate (85 mg) and naproxen sodium (500 mg). Both sumatriptan and naproxen have been approved in Canada for over 15 years. The dose of each component product falls within the recommended Canadian daily and maximum doses of each of the individual monotherapies.

Given the market history of both sumatriptan and naproxen, an abbreviated non-clinical package was provided for the combination product.

The clinical program consisted of two pivotal Phase 3 studies (MT400-301 and MT400-302) in support of the indication. These two studies were conducted in subjects with moderate to severe migraine with or without aura. They were single attack studies in adults aged 18-65 years of age, with at least a 6 month history of migraine. The primary endpoints were 2 hour pain relief (no or mild pain 2 hours after taking the investigational product), incidence of migraine symptoms (phonophobia, photophobia and nausea) at 2 hours, and superiority of Suvexx over the individual components (sumatriptan and naproxen) for sustained pain-free (no pain) from 2 to 24 hours.

The efficacy of Suvexx was supported by all primary endpoints measured with the exception of nausea in study MT400-301, which did not differ statistically relative to placebo. This lack of statistical significance was not considered of great concern as there was an imbalance of nausea in patients at baseline in that study. In addition, the trends showed a greater decrease in nausea in the Suvexx group relative to the placebo group; nausea was 7% higher in the Suvexx group than in placebo at baseline, 1% lower at 2 hours postdose and statistical significance was reached at 4 hours. Further, when subjects were separated into those that had nausea at baseline and those that did not (an a priori subset analysis), among the subjects with nausea at baseline, subjects treated with Suvexx had a higher nausea-free rate at 2 hours (52%) compared to the subjects in the placebo treatment group (43%). Thus, although not significant in one study, the trends supported a reduction in nausea and this endpoint reached statistical significance in the second study (MT400-302).

Suvexx was also found statistically superior over each of its constituent ingredients in sustained pain-free from 2 to 24 hours. Both pivotal studies demonstrated this effect, suggesting a sustained effect that is better than either component alone.

In support of the findings in the pivotal studies, 10 additional non-pivotal placebo-controlled studies supported the efficacy of Suvexx when looking at the 2 hour pain-free and/or sustained pain-free endpoints. A long-term open-label study also supported the safety of Suvexx treatment up to one year.

No new safety signals beyond those already known for sumatriptan and naproxen monotherapies have arisen since Treximet was approved in the United States more than 10 years ago. There does not appear to be any concerning additive safety issues by combining the two monotherapies together, and both individual components have a long safety history in Canada. The key safety issues of concern included in the Product Monograph (PM) are the cardiovascular and gastrointestinal risks, highlighted in the boxed Serious Warnings. Also, Suvexx is contraindicated in the PM for patients with coronary artery disease and conduction disorders, history of ischemias, vascular diseases, uncontrolled hypertension, bleeding disorders, gastrointestinal disorders, or during third trimester pregnancies.

Taken together, Suvexx is the combination of two products that have an acceptable safety profile and the safety does not appear to be exacerbated by their combination. These safety risks are well known by physicians and pharmacists due to the long history of the monotherapies on the Canadian market and are well documented in the PM. Suvexx has better efficacy than its individual components alone. For these reasons, Suvexx demonstrates a positive benefit-harm-uncertainty balance.