Study findings revealed statistically significant results at week 4 for the 100-U dose compared to placebo. The 75-U dose, while effective, did not achieve statistical significance.
Olaf Michel, PhD
IncobotulinumtoxinA (Xeomin, Mertz) has shown success in treating sialorrhea in Parkinson disease (PD), among other neurological conditions, according to new findings of a clinical trial.
Presented at the American Academy of Neurology's (AAN) 70th Annual Meeting in Los Angeles, California, by author Olaf Michel, PhD, the phase 3 Sialorrhea in Adults Xeomin Investigation (SIAXI) study evaluated the safety and efficacy of injections of incobotulinumtoxinA at a low dose of 75 U and a high dose of 100 U compared to placebo.1
The findings revealed that the 100 U dose showed statistically significant results at week 4 compared to placebo (P
<.005), while the 75-U dose did not achieve significance despite being more effective than the sham therapy.
“Uncontrolled sialorrhea is a very troublesome and disabling symptom associated with Parkinson’s disease and other various neurological conditions,” said Michel, the vice-chairman of the department of rhinology, head, and neck of the University Hospital of Vrije Universiteit Brussel, in Belgium.
In total, the trial randomized patients 2:2:1 to 100-U incobotulinumtoxinA (n = 74), 75-U incobotulinumtoxinA (n = 74), or placebo (n = 36). By percentage, sialorrhea etiologies were reported at 70.6% with PD, 17.9% with stroke, 8.7% with atypical Parkinson syndromes, and 2.7% with traumatic brain injury. Dosing and injection sites were 15 U into each submandibular gland and 22.5 U into each parotid gland for the lower-dose group, and 20 U into each submandibular gland and 30 U into each parotid gland in the higher-dose group. Patients were followed for 16 ±2 weeks post-injection.
The injection sites were localized by anatomical landmarks in 39.2%, 44.6%, and 50% of the 75 U, 100 U, and placebo-treated patients, respectively, while ultrasound guidance was used in the remaining respective 60.8%, 55.4%, and 50% of patients.
The 100-U group observed mean changes in unstimulated salivary flow rate (uSFR), a co-primary outcome, of -0.13 g/min at week 4 (P
= .004), -0.13 g/min at week 8, -0.12 g/min at week 12, and -0.11 g/min at week 16, all of which were statistically significant. The 75-U group experienced significant declines in uSFR at week 8 (-0.08 g/min) and week 12 (-0.10 g/min). The effect of the 75-U dose declined by week 16.
Measurements by the Global Impression of Change Scale (GCIS) were observed at weeks 4 (P
= .002), 8, 12, and 16 for the 100-U group, and weeks 8 and 12 for the 75-U group.
There were not any relevant differences in patient outcomes based on the injection technique using anatomical landmarks nor ultrasound guidance, and no unexpected adverse effects were recorded. “Both doses of incobotulinumtoxinA were safe and well tolerated over the whole time,” Michel said. Although, he added that “the safety profile is in favor of a higher dose of incobotulinumtoxinA.”
The study concluded that incobotulinumtoxinA (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.
“We can say that single injections of incobotulinumtoxinA in doses of 75 U or 100 U led to a clinical improvement in sialorrhea due to PD or other neurological conditions up to 16 weeks, but only the 100U dose resulted in statistically significant benefits to the coprimary endpoints at 4 weeks,” said Michel. “The effect was further increased during the 3 additional treatments in the extension period.”
On March 14, 2018, the US Food and Drug Administration (FDA) accepted a supplemental Biologics License Application (BLA) from Merz for the therapy for the treatment of chronic sialorrhea due to PD or other neurologic conditions in adult patients.2
The Prescription Drug Fee User Act action date was set for Q4 of 2018. If approved, it would be the only neurotoxin with this indication in the US.
“Sialorrhea is a common problem among people living with neurological disorders, causing added physical and psychosocial challenges for patients as well as caregivers,” David Dobrowski, the vice president of Research and Development, at Merz North America, said at the time. “We believe Xeomin can help manage excessive drooling, and we look forward to continuing to work closely with the FDA as they review our application.”
1. Jost W, Friedman A, Michel O, et. al.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. Presented at: 70th Annual American Academy of Neurology Meeting; April 24, 2018. neurology.org/content/90/15_Supplement/S2.007. Accessed April 24, 2018.
2. FDA Accepts for Filing Supplemental Biologics License Application (sBLA) for Xeomin® (incobotulinumtoxinA) in Adult Patients with Sialorrhea [press release]. Raliegh, NC: Merz North America Corporate Communications; March 14, 2018. Accessed April 24, 2018.