Regulatory Decision Summary for Botox

The purpose of this Supplement to a New Drug Submission (SNDS) was to seek market authorization, pursuant to section C.08.004 of the Food and Drugs Regulations to request a label update for Botox for adult upper limb spasticity indication to include updated dosing guidance for several, an increase in the maximum dose from 360 Units (U) to 400 U for the treatment of adult upper limb spasticity across multiple joints, and to remove the requirement for a poststroke etiology from the upper and lower limb spasticity indications.

The efficacy and safety of Botox for the treatment of adult upper limb spasticity was evaluated in three randomized, multicentre, double-blind, placebo-controlled studies (Studies 4, 5 and 6). Studies 4 and 5 provided sufficient evidence to support the hand/wrist and elbow flexor muscle labeling.

Study 4 was designed to give direct comparison information between the current standard of care and the increased dose of 400 U for up to 12 weeks for the treatment of upper limb spasticity (elbow flexors). The study met its primary endpoint, the responder rate was 68% in the treatment group (400 U) and 50.8% in the control group, the difference was 18.1% (95% Confidence Interval [CI] 1.1 to 35). Results are suggestive of some improvement in muscle tone, which can be associated with clinical improvement, but not necessarily for all responders.

Study 5 was considered supportive and enrolled 53 post-stroke adult patients with upper limb spasticity. Patients received a single fixed-dose, fixed-muscle treatment of either Botox 300 Units (150 Units elbow; 150 Units shoulder), or placebo, divided across defined muscles of the elbow and shoulder in a single limb. The duration of follow-up was 12 to 16 weeks. The mean change from baseline in elbow flexor muscle tone on Modified Ashworth Scale (MAS) was -1.47 compared to -0.74 in the placebo group, and the Modified Ashworth Scale (MAS) elbow flexors response rate was 72.2% compared to 47.1% respectively.

Study 6 was a two-part Phase 3b multicenter study with one double-blind-placebo controlled treatment cycle of placebo or Botox up to 400 U, followed by an open-label (OL) extension phase with up to 4 treatments over 1 year. A total of 274 patients were enrolled. For the hand/wrist muscles, the resistance to passive movement scale (REPAS) score at week 6 was -0.5 in the treatment group, and -0.3 in the control group. In other supporting studies (191622-056 and 057), the wrist muscles tone change from baseline at week 6 was -0.7 in the Botox >250 U, and -0.2 in the Botox<250 U.

There was an acceptable safety profile that was consistent with the established safety profile of Botox, and the provided evidence is sufficient to add the requested hand/wrist and elbow flexor muscle to the Product Monograph.

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

A Notice of Compliance (NOC) was issued.

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