The Astellas Pharma agent earned an indication for children aged 3 years and older, after its original overactive bladder indication in 2012.
Salim Mujais, MD
The FDA has approved mirabegron extended-release tablets (Myrbetriq) and mirabegron for extended-release oral suspension (Myrbetriq Granules), both developed by Astellas Pharma, for the treatment of neurogenic detrusor overactivity (NDO) in children aged 3 years and older.1
The Astellas agent is also indicated for overactive bladder in adult patients, earning its original approval in 2012. A recommended dosage for the extended-release oral suspension for adults has not been determined. The causes of NDO in children can include transverse myelitis, spinal cord injury, spina bifida, and multiple sclerosis.
“Today’s action is a positive step for the treatment of NDO in young patients,” said Christine P. Nguyen, MD, director, FDA’s Division of Urology, Obstetrics and Gynecology, Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, Center for Drug Evaluation and Research, in a statement. “Mirabegron, the active ingredient in Myrbetriq and Myrbetriq Granules, works by a different mechanism of action from the currently approved treatments, providing a new treatment option for these young patients. We remain committed to facilitating the development and approval of safe and effective therapies for pediatric NDO patients.”
In January, at the time of the new drug application acceptance, Salim Mujais, MD, senior vice president and head, Medical Specialties, Astellas, said in a statement that “mirabegron has the potential to expand the repertoire of treatments available for these children, offering a favorable balance of efficacy and tolerability.”2
The efficacy of the 2 formulations in the treatment of pediatric NDO was established in an open-label single group assignment study of 86 patients ages 3 to 17 years old, titled CROCODILE (NCT02751931). The patients were assessed in a group of children aged 3 to less than 12 years (n = 55) and a group of adolescents aged 12 to less than 18 years (n = 35).
Improvements were observed in patients’ maximum cystometric capacity (MCC) at 24 weeks, which was significantly improved in both treatment groups: those aged 3 to less than 12 years (72.09 mL [95% CI, 45.28-98.89]; P <.001) and those aged 12 to less than 18 years (113.21 mL [95% CI, 78.95-147.47]; P <.001).
Additionally, secondary outcome measures such as the number of detrusor contractions (>15 cm H20), the volume of urine held until first detrusor contraction (>15 cm H20), and the number of daily urine leakage episodes all showed improvements after 24 weeks of treatment.
The most common adverse events (AEs) were urinary tract infection, nasopharyngitis, constipation, and headache. In total 60% (n = 33) of the children under 12 younger age group and 58.1% (n = 18) of the adolescent under 18 years but older than 12 years group.
“Myrbetriq and Myrbetriq Granules may increase blood pressure and may make blood pressure worse in patients with a history of high blood pressure. Myrbetriq and Myrbetriq Granules may cause angioedema, an allergic reaction with swelling of the lips, face, tongue or throat. Patients should promptly discontinue Myrbetriq and Myrbetriq Granules and seek medical attention if angioedema associated with upper airway swelling occurs, as this may be life-threatening,” the FDA noted in its statement.
These approvals join the February go-ahead for onabotulinumtoxinA (Botox; Allergan/AbbVie), which won an indication for the treatment of NDO in pediatric patients aged 5 years or older that are intolerant of or do not respond well to anticholinergic medication. OnabotulinumtoxinA was evaluated for the treatment of pediatric NDO in a randomized, double-blind, phase 3 study (NCT01852045) in more than 100 patients as well as a long-term extension study. Data showed that intradetrusor administration of onabotulinumtoxinA reduced daytime urinary incontinence episodes, lowered maximum bladder pressure, and increased bladder capacity at week 6.3