Regulatory Decision Summary for Xeomin

This submission was filed in order to seek approval for the expanded use of Xeomin (botulinumtoxin A) for the treatment of lower limb spasticity in adult patients. The sponsor submitted two placebo-controlled trials in support of this indication and also referred to an open-label study that was previously submitted in support of the upper limb spasticity indication. After evaluation of the submitted data package, Health Canada authorized Xeomin for the treatment of post-stroke spasticity of the lower limb involving the ankle and foot in adults.

Xeomin has previously been authorized for indications relating to blepharospasm, cervical dystonia, chronic sialorrhea, and spasticity of the upper limb.

Authorization of this indication for Xeomin was based on two pivotal placebo-controlled, double-blind, randomized Phase 3 trials.

One placebo-controlled Phase 3 study (study 3002) was conducted at study sites in Europe and North America in 290 patients with post-stroke spasticity of the lower limb. The study comprised a double-blind, single-dose main phase and an open-label extension phase. Study 3002 did not meet its primary endpoint of change from baseline in the Ashworth Score of plantar flexors at Week 4, possibly due to study design flaws.

The second placebo-controlled Phase 3 study (study 3098) was conducted at study sites in Japan in 219 patients with post-stroke spasticity of the lower limb. The study comprised an open-label lead-in tolerability period, a double-blind single-dose main phase, and an open label extension phase. Study 3098 showed a statistically significant difference between Xeomin and placebo on the primary endpoint of area under the curve for the change from baseline to the end of the main phase (12 weeks) in the Modified Ashworth Score plantar flexors score, and this result was supported by the secondary endpoints.

In both trials, the type and frequency of adverse reactions reported in adults treated with Xeomin for lower limb spasticity were consistent with the known safety profile of Xeomin and that of other BoNT A products. One new safety issue (risk of fall) was identified, and all identified risks are defined in the Canadian Product Monograph (CPM).

The recommended dose of Xeomin is a maximum of 400 units per treatment session, administered intramuscularly. Recommended muscles, dose per muscle and number of injection sites per muscle are defined in a dosage guide in Section 4.2 of the approved CPM.

The final recommendation for this product was based on the totality of evidence, including clinical data and comparisons with labels of other botulinumtoxin A products marketed in Canada.

A Risk Management Plan (RMP) for Xeomin was reviewed by Health Canada and considered acceptable.

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

Overall, the benefit-harm-uncertainty profile was favourable for Xeomin for the approved indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

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