The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion, recommending the granting of a marketing authorization for BETMIGA[ (mirabegron) for the symptomatic treatment of urgency, increased micturition frequency and/or urgency incontinence as may occur in adult patients with overactive bladder (OAB) syndrome. 

The opinion now needs ratification by decision of the European Commission which is expected within the next 74-90 days. If approved, mirabegron will be the first in a new class of OAB treatment, offering healthcare professionals an alternative option to antimuscarinics (currently the only licensed oral treatment option) when treating patients with OAB.

Mirabegron is a once daily oral beta3-adrenoceptor agonist with a distinct mechanism of action compared to antimuscarinics, the current treatment standard.[1] Antimuscarinics work by binding to muscarinic receptors in the bladder and inhibiting involuntary bladder contractions. Mirabegron works by stimulating the beta3 receptors in the detrusor muscle of the bladder[2] causing relaxation of the bladder muscle during the storage phase of the micturition cycle. This improves the storage capacity of the bladder without inhibiting bladder voiding.[3]

 The positive opinion was reached after the CHMP reviewed comprehensive clinical trial evidence from 7 phase II / III studies in which over 5,000 patients received mirabegron, including three Phase III double-blind, randomized controlled trials conducted in the US and Europe-Australia.[4],[5],[6] In the trials, mirabegron demonstrated superior efficacy compared to placebo in the treatment of symptoms of OAB, with patients needing to visit a toilet significantly less frequently and experiencing fewer incontinence episodes.[4],[5],[ 6] In terms of quality of life, treatment of the symptoms of OAB with mirabegron once daily has also demonstrated statistically significant improvements over placebo on quality of life measures such as treatment satisfaction and symptom bother.[7] 

Overactive bladder (OAB) is characterized by symptoms of urinary urgency, with or without urgency incontinence, usually with increased daytime frequency and nocturia (awakening at night one or more times to empty the bladder).[8]

OAB is a common condition. A survey of over 16,000 adult men and women in six European countries revealed that 17% of respondents had symptoms of OAB.[9] Prevalence of OAB increases with age, with 30% to 40% of those aged over 75 years affected.[9] OAB can also have a major impact on quality of life. In the survey, a majority (65%) of respondents indicated their daily lives were adversely affected.[9]

Mirabegron is a once daily oral β3-adrenoceptor agonist discovered and developed by Astellas. It is the first compound submitted for regulatory approval in this new class of treatment for OAB, using a distinct mechanism of action compared to antimuscarinics, the current treatment standard.[1] Antimuscarinics work by binding to muscarinic receptors in the bladder and inhibiting involuntary bladder contractions. Mirabegron works by stimulating the β3 receptors in the detrusor muscle of the bladder causing relaxation of the bladder muscle during the storage phase of the micturition cycle.[2] This improves the storage capacity of the bladder without impeding bladder voiding.[3]

Astellas submitted a New Drug Application and Market Authorisation Application for mirabegron to the U.S. Food and Drug Administration and the European Medicines Agency in August 2011 and received FDA approval on 28th June 2012, and CHMP opinion today. In Japan, Astellas was granted marketing approval under the trade name of BETANIS® tablet in July 2011. Additionally, there is a recently completed multiregional Phase III study in China, Korea, Taiwan, and India.

References

(1)Khullar V et al. Efficacy of mirabegron in patients with and without prior antimuscarinic therapy for overactive bladder (OAB): Post-hoc analysis of a prospective, randomised European-Australian phase III trial. EAU 2012 Abstract AM12-2389: 684

(2) Takasu T et al. Effect of (R)-2-(2-aminothiazol-4-yl)-4′-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function. J Pharmacol Exp Ther 2007; 321: 642-7

(3) Tyagi P et al. Mirabegron: safety review Expert Opin. Drug Safety 2011;10.2: 287-294

(4) Nitti V et al. The efficacy and tolerability of mirabegron, a potent and selective β3-adrenoceptor agonist, compared with placebo and tolterodine slow release in patients with overactive bladder - results from a North American Phase III trial. Presented at ICS 2011.

(5) Khullar V et al. The efficacy and tolerability of mirabegron, a potent and selective β3-adrenoceptor agonist, compared with placebo and tolterodine slow release in patients with overactive bladder - results from a European-Australian Phase III trial. Presented at ICS 2011

(6) Van Kerrebroeck P, Barkin J, Castro-Diaz D et al. Randomised, double-blind, placebo-controlled Phase III study to assess the efficacy and safety of mirabegron 25 mg and 50 mg once daily in overactive bladder (OAB). Presented at ICS 2012.

(7) Nitti V et al. Mirabegron improves patient-reported outcomes in patients with overactive bladder syndrome - results from a North-American study. Presented at AUA 2011

(8) Abrams P. et al. Reviewing the ICS 2002 Terminology Report: The Ongoing Debate. Neurourol Urodyn 2006; 25: 293-294

(9) Milsom I, Abrams P, Cardozo L, et al. How widespread are the symptoms of an overactive bladder and how are they managed? A population-based prevalence study. BJU Int 2001; 87(9): 760-6