The sBLA for onabotulinumtoxinA is supported by the findings from a randomized, double-blind phase 3 study evaluating the safety and efficacy of onabotulinumtoxinA in more than 100 pediatric patients.
Mitchell F. Brin, MD
The FDA has accepted a supplemental biologics license application (sBLA) from Allergan for onabotulinumtoxinA (Botox) to expand its prescribing information to include the treatment of signs and symptoms related to detrusor overactivity associated with an underlying neurologic condition, such as spina bifida and spinal cord injuries. The indicated patient population would be pediatric patients aged 5 to 17 years who have inadequate or intolerant responses to anticholinergic medications.1
Allergan’s submission is based on the findings from a randomized, double-blind phase 3 study evaluating the safety and efficacy of onabotulinumtoxinA in more than 100 pediatric patients with neurogenic detrusor overactivity and its long-term extension. The Prescription Fee User Drug Act (PDUFA) action date is anticipated to be in the first quarter of 2021.
"The FDA acceptance of this application underscores our ongoing commitment to pursuing the full potential of BOTOX® to serve patients across a wide spectrum of diseases and clinical needs," Mitchell F. Brin, MD, senior vice president, chief scientific officer, BOTOX® & Neurotoxins, AbbVie, said in a statement. "Children living with neurogenic detrusor overactivity currently have limited options when they fail anticholinergic medications and prior to surgical intervention.”
OnabotulinumtoxinA is already indicated for a number of conditions, including overactive bladder symptoms, incontinence caused by neurologic disease, headache prevention in those with chronic migraine, muscle stiffness in those with upper and lower limb spasticity, and abnormal head position and neck pain associated with cervical dystonia, among others.
“If approved, BOTOX® will be the first neurotoxin treatment approved for use in treating detrusor overactivity in pediatric patients with an underlying neurologic condition who are not adequately managed by anticholinergic medications," Brin added.
Children often faced neurogenic detrusor overactivity due to transverse myelitis, spinal cord injury, and spina bifida, which is estimated to affect 1500 to 2000 of the more than 4 million babies born in the United States each year. Of those with spina bifida, more than 90% experience urinary symptoms.
"Over time, many pediatric patients with underlying neurologic conditions experience bladder and kidney damage, and treatment is critical," said Paul F. Austin, MD, FAAP, chief, Pediatric Urology, Texas Children's Hospital, and professor of urology, Baylor College of Medicine, in a statement. "Current treatment options often include anticholinergic medications, where long-term use needs to be considered carefully, in addition to surgery. The favorable BOTOX® clinical results for the treatment of pediatric patients with neurogenic detrusor activity are promising as we look to address unmet and ongoing needs in children and adolescents."
In the phase 3 assessment (NCT01852045), the total study population of 113 patients had an average of daily daytime urinary incontinence episodes of 3.16 (range, 0.5 to 29.5), with those averages by dose group being 2.81 (range, 0.8 to 6.7) for the 50 U group (n = 38), 2.99 (range, 1.3 to 6.1) in the 100 U group (n = 45), and 3.68 (range, 0.5 to 29.5) in the 200 U group (n = 30).2
The change from baseline to Day 28 in the daily average frequency of daytime urinary incontinence episodes for the 50 U group was —1.30 (standard error [SE], 0.205), the 100 U group was –1.30 (SE, 0.189), and 200 U group was –1.34 (SE, 0.245). The change from baseline in average urine volume at first-morning catheterization was 21.93 mL (SE, 14.676), 34.90 mL (SE, 13.580), and 87.49 mL (SE, 17.808), for the 50, 100, and 200 U groups, respectively.
1. FDA Accepts Supplemental Biologics License Application (sBLA) for BOTOX® (onabotulinumtoxinA) for the Treatment of Pediatric Patients with Neurogenic Detrusor Overactivity [press release]. North Chicago, IL. AbbVie. June 22, 2020. Accessed June 26, 2020.
2. Study of OnabotulinumtoxinA (BOTOX®) for Urinary Incontinence Due to Neurogenic Detrusor Overactivity in Pediatric Patients. ClinicalTrials.gov website. Updated November 21, 2019. Accessed June 29, 2020. clinicaltrials.gov/ct2/show/results/NCT01852045.