FDA Approves IncobotulinumtoxinA Pediatric Indication for Chronic Sialorrhea

Heakyung Kim, MD

Merz Therapeutics announced that its investigational agent incobotulinumtoxinA had its supplemental biologics license application (sBLA) accepted by the FDA for the treatment of patients aged 2 years and older with chronic sialorrhea.

Marketed as Xeomin, the treatment becomes the first and only FDA-approved neuromodulator with this indication, after previously being granted a priority review designation upon sBLA filing acceptance by the FDA.

The basis of this approval comes from a phase 3 prospective, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of incobotulinumtoxinA in 255 children and adolescents aged 2 to 17 years. Results showed that the treatment significantly reduced unstimulated Salivary Flow Rate (uSFR), or the primary end point, compared with placebo at week 4 among patients aged 6 to 17 years, and sustained efficacy over 64 weeks.

The study’s second primary end point, Global Impression of Change Scale (GICS) score, was also significantly improved and sustained over 64 weeks with the treatment compared with placebo.

"The current standard of care for sialorrhea is pharmacological management with anticholinergics such as glycopyrrolate or a scopolamine patch,” Heakyung Kim, MD, A. David Gurewitsch Professor of Rehabilitation and Regenerative Medicine and Professor of Pediatrics, Columbia University Medical Center, told NeurologyLive. “However, these medications could cause significant side effects such as urinary retention, increased mucus plugging, and blurry vision. Therefore, botulinum toxin injection, including Xeomin, which he will be given locally, decreasing the risk of systemic side effects.”

Improvements in chronic sialorrhea increased with each injection cycle of the treatment compared with baseline. Patients between the ages of 2 to 5 years, all of whom received incobotulinumtoxinA and not placebo, had comparable GICS scores.

There were no observations of clinical resistance or secondary treatment failure due to neutralizing antibodies (Nab). This finding supports the importance of the treatment’s unique purification process through XTRACT technology, according to Merz.

The safety findings were similar to previous adult and children pediatric studies and in line with the known safety profile. Bronchitis, headache, and nausea/vomiting were among the most common adverse events (AEs) affecting ≥1% of patients aged 6 to 17 years. In children aged 2 to 5 years, nasopharyngitis was the most common adverse reaction.

"Pediatric patients living with chronic sialorrhea have suffered with this debilitating condition without a viable long-acting treatment option,” Kevin O’Brien, president of North America, Merz Therapeutics, said in a statement. “Merz Therapeutics is proud to offer XEOMIN, the first and only FDA-approved neurotoxin treatment that is uniquely purified to provide safe and effective treatment for this condition.”

Notably, IncobotunlinumtoxinA has a number of serious adverse effects that may be life threatening. These include problems swallowing, speaking, or breathing, which may result in death for those who deal with these issues to begin with. Additionally, the treatment may cause the spread of toxin effects, including areas of the body away from the injection site, leading to botulism.

Other notable adverse effects caused by incobotulinumtoxinA include injury to the cornea in people treated for blepharospasm, as well as allergic reactions such as itching, redness, swelling, rash, wheezing, trouble breathing, or dizziness.

It is not known if the treatment is safe and effect in children younger than 2 years of age for the treatment of chronic sialorrhea or upper limb spasticity, and under 18 years of age for the treatment of cervical dystonia or blepharospasm.

"Having Xeomin approved to treat another symptom that children living with movement disorders experience is an important milestone for patients, caregivers and healthcare providers,” Elizabeth Moberg-Wolff, MD, pediatric and brain injury PM&R physician, Pediatric Rehabilitation Medicine Associates, said in a statement.

REFERENCE

FDA Approves pediatric indication for Xeomin (incobotulinumtoxinA) for the treatment of chronic sialorrhea. News release. Merz. December 21, 2020. Accessed December 21, 2020. https://www.merzusa.com/news/pediatricsialorrhea/