Efficacy and Safety of IncobotulinumtoxinA for Treatment of Sialorrhea: A Multicenter, Phase 3 Study in Japan

Background: Sialorrhea, caused by various neurological diseases, impairs patient health and quality of life. After the results of a randomized controlled trial, incobotulinumtoxinA was approved for the treatment of chronic sialorrhea in the United States and Europe; however, no pharmacotherapy has been approved in Japan. Objective: The aim was to evaluate the efficacy and safety of incobotulinumtoxinA treatment for chronic sialorrhea in a single-arm phase 3 study in Japan. Methods: Patients with chronic sialorrhea caused by neurological diseases (Parkinson's disease, atypical parkinsonism, and stroke, group A) and broader diseases (eg, muscular dystrophy and amyotrophic lateral sclerosis, group B) were enrolled. IncobotulinumtoxinA 100 U was injected into the salivary glands once every 16 weeks for 48 weeks. A primary endpoint was assessed in group A, whereas secondary endpoints and safety were assessed in both groups. Results: From November 2021 to August 2023, 92 patients (58 and 34 in groups A and B, respectively) received incobotulinumtoxinA at 28 institutions. The primary endpoint, the least square mean (standard error) of change in unstimulated salivary flow rate from baseline to 4 weeks, was −0.08 (0.009, 95% confidence interval [CI]: −0.10, −0.06) g/min, achieving the prespecified efficacy criteria (upper limit of the 95% CI <−0.04). The secondary endpoints were consistent across efficacy measures, indicating that reduced salivary secretion and improved drooling symptoms persisted for 48 weeks. The most common adverse events were dry mouth and dysphagia. Conclusions: The first study in Japan confirmed the efficacy of incobotulinumtoxinA treatment for chronic sialorrhea with good patient tolerability and no new safety concerns.