Data presented at the 26th Annual Congress of the European Association of Urology in Vienna on 21st March show that mirabegron significantly improves urinary incontinence and frequency - key symptoms of overactive bladder.
"The findings of these studies are very exciting," said Vik Khullar of St Mary's Hospital, London, lead investigator for one of the two trials. "As these two studies suggest, mirabegron has the potential to provide an effective new treatment option for OAB patients who continue to suffer from the distressing symptoms of incontinence and frequent need to pass urine."
The majority of existing treatments for overactive bladder, including oxybutynin, tolterodine, solifenacin and trospium, act on muscarinic receptors to inhibit bladder contraction. By contrast, mirabegron activates β3 adrenoceptors, thereby improving the storage capacity of the bladder.
The two randomised, double-blind parallel-group trials of mirabegron took place in the US and Canada (n=1328) and in Europe and Australia (n=1978). Investigators randomised patients with at least a 3-month history of overactive bladder symptoms to receive once-daily treatment with mirabegron 50mg or 100mg, or placebo (or, in the European/Australian trial, sustained-release tolterodine 4mg). More than 70% of patients in each trial were female.
After 12 weeks, patients in the mirabegron groups showed significant improvements from baseline in the two primary endpoints:
Incontinence episodes per 24 hours:
- North American trial: reduction of 1.47–1.63 versus 1.13 with placebo (p<0.05)
- European/Australian trial: reduction of 1.46–1.57 versus 1.17 with placebo (p<0.05)
Micturitions per 24 hours:
- North American trial: reduction of 1.66–1.75 versus 1.05 with placebo (p<0.05)
- European/Australian trial: reduction of 1.77–1.93 versus 1.34 with placebo (p<0.05)
The incidence of adverse events was similar for mirabegron, placebo and tolterodine.
Manufacturer Astellas plans to submit a regulatory filing for mirabegron later this year. If approved, mirabegron would be the first oral treatment for overactive bladder with a completely new mode of action since the launch of oxybutynin several decades ago.