Regulatory Decision Summary for Xeomin
Review decision
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
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What was the purpose of this submission?
Xeomin is a muscle relaxant produced by the bacterium Clostridium botulinum. Botulinum neurotoxin type A blocks cholinergic transmission at the neuromuscular junction and at the salivary glands by inhibiting the release of Acetylcholine (Ach) from peripheral cholinergic nerve terminals. Xeomin was approved for marketing in Canada in March 2009 as a muscle injection for the treatment of blepharospasm, cervical dystonia and upper limb spasticity in adult subjects. The current SNDS proposed a new indication of parotid and submandibular gland injections with Xeomin for the treatment of chronic sialorrhea in adult patients with neurological disorders. Chronic sialorrhea is usually a consequence of neurological disease or injury requiring long-term treatment.
A Notice of Compliance (NOC) was recommended and issued.
Why was the decision issued?
A phase 3 randomized, double-blind, placebo-controlled and multicenter clinical study was conducted in 184 patients with chronic sialorrhea resulting from the neuromuscular disorders (i.e., Parkinsons disease, stroke or traumatic brain injury). The study consisted of a 16-week main phase and followed by a 64-week extension period (EP) of dose-blinded repeated treatment. In the double-blind main phase, patients were randomised (36:74:74) to receive parotid and submandibular gland injections of placebo or Xeomin at total doses of 100 units (U) or 75 U. The co-primary efficacy endpoints were the changes in unstimulated Salivary Flow Rate (uSFR) and the Global Impression of Change Scale (GICS) at week 4 post-injection. The patients uSFR and GICS scores were statistically significantly improved at week 4 after the injection with Xeomin at the dose of 100 U compared to placebo. The benefits persistence was observed for 8-12 weeks after the treatment, in the secondary endpoints. The patients have received up to 3 additional treatments for total of 64 weeks in the extension period of the study. The results support the findings of the main phase of the study showing continued treatment benefits of Xeomin in patients with neurological disorders.
Adverse drug reactions (ADRs) reported (>1%) were dry mouth, dysphagia, paresthesia and speech disorder mainly related to the diffusion of Botulinum neurotoxin type A from the target muscle to adjacent muscles. The ADRs were observed within the first week after treatment and were temporary in nature. No safety signal was identified and no patient deaths were identified to be related to the study.
The intraglandular injection of Xeomin was demonstrated to relieve symptoms of chronic sialorrhea (SIA), preventing complications in patients with neuromuscular disorders. The benefits outweigh the risks.
A NOC is recommended.
The recommended total dose of Xeomin for parotid and submandibular glands injections is 100 U per treatment. View the Product Monograph for details.
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.