SIAXI: Efficacy and safety of Xeomin (incobotulinumtoxinA) for the treatment of sialorrhea in Parkinson’s disease (PD) and other neurological conditions: Results of a Phase III, placebo-controlled, randomized, double-blind study (S2.007)

Objective: To investigate the efficacy and safety of Xeomin for treating troublesome sialorrhea.

Background: Uncontrolled sialorrhea results from various causes including Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). Botulinum toxin A/B improves sialorrhea in PD and ALS, as shown here with Xeomin.

Design/Methods: Eligible subjects had chronic troublesome sialorrhea due to PD or atypical parkinsonism/stroke/traumatic brain injury, and were randomly assigned (double-blinded) to Xeomin 75U/100U or placebo. Dosing and injection sites were: 15/20U into each submandibular gland; 22.5/30U into each parotid gland in the lower/higher dose group. Subjects were followed for 16±2 weeks after injection. Co-primary outcomes were: unstimulated salivary flow rate (uSFR) at week 4 vs baseline and Global Impression of Change Scale (GICS) 4 weeks post-injection.

Results: 184 subjects were enrolled and received either 75U (n=74); 100U (n=74); or placebo (n=36). Sialorrhea etiologies by percentage were: PD 70.6%, atypical Parkinson syndromes 8.7%, stroke 17.9%, traumatic brain injury 2.7%. Injection sites were localized by anatomical landmarks in 39.2%, 44.6%, 50% and ultrasound guidance was used in 60.8%, 55.4%, 50% in the 75U, 100U and placebo-treated subjects, respectively. Both coprimary outcomes uSFR and GICS improved significantly and reached statistical significance in the 100U treatment arm at week 4 vs baseline pre-injection vs placebo (p<0.005). 75U was more effective than placebo (not statistically significant). There was significant improvement in both uSFR and GICS at Weeks 8/12 post-injection in both active treatment groups, with maintained improvement in the uSFR in both dose groups at the last observation point at week 16. Further measures of efficacy showed clinically relevant improvement. No relevant differences in outcomes based on injection technique using anatomical landmark vs ultrasound guidance were observed, with no unexpected side effects.

Conclusions: Xeomin (75U/100U) effectively treated troublesome sialorrhea in PD and other neurological conditions at a parotid/submandibular dose ratio of 3:2, for up to 16 weeks.

Study Supported by: Merz Pharmaceuticals GmbH.

Disclosure: Dr. Jost has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Allergan plc, Ipsen, and Merz. Dr. Friedman has received research support from Merz. Dr. Michel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with MERZ GmbH Germany. Dr. Flatau-Baque has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merz Pharmaceuticals GmbH. Dr. Flatau-Baque has received royalty, license fees, or contractual rights payments from Merz Phamaceuticals GmbH. Dr. Csikós has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merz Pharmaceuticals GmbH. Dr. Csikós has received royalty, license fees, or contractual rights payments from Merz Pharmaceuticals GmbH. Dr. Blitzer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merz. Dr. Blitzer has received research support from Merz.