Discovery history and clinical development of mirabegron for the treatment of overactive bladder and urinary incontinence

Overactive bladder (OAB) and urinary incontinence, although not life-threatening, are very bothersome chronic health conditions. The limitations of current pharmacological treatment urge the need for novel drugs with alternative mechanisms of action. Huge efforts in this area of research led to the synthesis of several selective and potent β3-adrenoceptor agonists that gained relevance through research during the late 80s and 90s. Mirabegron was the first compound of this new class of drugs that showed preclinical efficacy in several models of storage bladder dysfunction, together with a favorable human pharmacological profile. Having passed the proof-of-concept stage, an extensive clinical development and pharmacology program was performed during the last 10 years, involving >10,000 individuals, before mirabegron was granted marketing approval.