Canadian authorities have approved Xeomin (incobotulinumtoxinA) for the treatment of chronic sialorrhea, or excessive drooling, associated with neurological diseases such as amyotrophic lateral sclerosis (ALS).
The decision makes Xeomin the first and only neurotoxin for chronic sialorrhea licensed for this indication in Canada. The therapy was approved for the same indication by the U.S. Food and Drug Administration in July 2018.
Sialorrhea is a common symptom among patients with progressively deteriorating neurological diseases such as Parkinson’s disease, cerebral palsy, and ALS, due to difficulties in swallowing and controlling facial muscles.
“The reality is that uncontrolled salivation is underestimated in many neurological diseases,” Michel Panisset, MD, with the Centre hospitalier de l’Université de Montréal, Canada said in a press release. “Left untreated, involuntary drooling or sialorrhea is an annoying and disturbing symptom that can have aesthetic, psychological and medical consequences in some patients.”
Xeomin, developed by Merz Therapeutics, is a purified form of the botulinum neurotoxin type A. It works by preventing the release of the neurotransmitter acetylcholine from nerve endings at muscles and salivary glands, which decreases saliva secretion. (Neurotransmitters are substances produced in response to nerve signals that act as chemical messengers.)
Xeomin’s approval for sialorrhea in Canada and in the U.S. was based on results from the SIAXI Phase 3 clinical trial (NCT02091739), which investigated whether the treatment outperformed a placebo at reducing saliva secretion, as well as the severity and frequency of chronic sialorrhea.
A total of 184 participants were assigned randomly to one of two doses of Xeomin (75U or 100U, 74 patients in each group), or a placebo (36 patients). After receiving a single dose of their assigned treatment in the placebo-controlled part, patients were eligible to join an open-label, extension part, in which all received three additional Xeomin injections, given at about 16-week intervals.
Results showed that both primary goals were met during the first stage of the trial, with the 100U dose of Xeomin leading to statistically significant improvements in unstimulated salivary flow rate and in the Global Impression of Change Scale, a common rating system used to assess treatments of neurological disorders.
These benefits were observed as early as four weeks after the injection, and were maintained until the end of the placebo-controlled phase (16 weeks). Notably, uncontrolled saliva secretion continued to decrease with additional doses over the 64 weeks of the open-label extension phase.
Sustained benefits also were observed throughout the 64 weeks in additional measures of efficacy, including reductions in drooling frequency and severity, as well as stable speech and swallowing scores.
Xeomin was well-tolerated overall, leading to similar rates of adverse side effects as the placebo. The most frequent side effects related to Xeomin were dry mouth and difficulty swallowing, all of which were mild-to-moderate in severity. No additional safety concerns were reported over the 64 weeks of treatment.
“I am very encouraged by the clear published evidence demonstrating Xeomin reduces salivary flow rates in patients suffering from sialorrhea due to neurological conditions such as Parkinson’s disease and related disorders,” said Anthony Lang, director of the Movement Disorders Program at University Health Network in Toronto.
“Based on the data and my own clinical experience in managing this challenging problem, XEOMIN has an established tolerability and safety profile and is an important option for treating chronic sialorrhea in adults,” added Lang.
This approval is the fourth indication for Xeomin in Canada. It was first approved in 2009 for the treatment of hypertonicity disorders in adults, characterized by muscle stiffness and trouble moving, including blepharospasm and cervical dystonia. It also was approved as a therapy for adults with stiff arms due to stroke.
“Merz Therapeutics is passionate about developing better outcomes for more patients and this latest Xeomin milestone demonstrates that commitment especially to Canada’s estimated 65,000 adult patients who suffer from chronic sialorrhea,” said Yannick Grosskreutz, country manager, Canada, for Merz Therapeutics.
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