BERKELEY, CA (UroToday.com) - Overactive bladder (OAB) is a prevalent condition, affecting an estimated 11.8% to 16.5% of adults worldwide.[1, 2] Although rarely life-threatening, the impact of OAB is substantial with respect to adverse effects on quality of life and co-morbidities as well as the economic burden. Traditionally, anti-muscarinic agents have been the primary pharmacologic therapy for the medical management of OAB. Although effective, persistence with anti-muscarinic therapy has been poor with discontinuation rates at 12 months ranging between 65% and 86%.[3] Modifications in delivery systems, modes of delivery, and differences in molecular structure/weight and muscarinic receptor affinity have provided for a more patient-centric treatment approach, but side effects such as constipation and dry mouth and concerns regarding the risk of cognitive dysfunction, particularly in high-risk patient populations, remain.
Recently, a new class of pharmacologic therapy, a beta-3 adrenoceptor agonist, has been approved for the treatment of OAB. A systematic review of the literature and mixed treatment comparisons demonstrated that mirabegron (a beta -3 adrenoceptor agonist) 50mg was as efficacious as anti-muscarinic agents in reducing urinary incontinence and urgency urinary incontinence episodes, although head-to-head comparisons are needed to confirm these results. In contrast to anti-muscarinic agents, which are thought to “prevent” detrusor contractions, beta 3-adrenoceptor agonists induce detrusor relaxation.[4]
Solabegron is a selective beta 3-adrenoceptor agonist under clinical investigation. Animal studies have demonstrated that intravenous administration of solabegron increases the micturition threshold without significantly affecting voided volume, voiding efficiency, or bladder contraction amplitude and duration.[5] A proof-of-concept study in incontinent women with OAB comparing solabegron 50mg, solabegron 125mg, and placebo demonstrated a statistically significant percentage change from baseline to week 8 in the number of incontinence episodes compared to placebo. Additionally, statistically significant differences compared to placebo were noted for other endpoints including:
- percentage reduction in incontinence episodes with solabegron 50mg and 125mg at week 4,
- actual reductions in micturitions for solabegron 125mg at weeks 4 and 8, and
- percentage and actual increase in volume voided with solabegron 125 mg at week 8.
Safety results demonstrated no significant difference from placebo in the incidence of dry mouth and constipation compared to placebo or in changes in ambulatory blood pressure, monitoring for both doses of solabegron. In addition to the potential use as a monotherapy for OAB, the role of combination therapy with solabegron is being explored and a U.S. patent (EP2600859A1) exists for a solabegron and oxybutynin combination therapy.[6]
As with anti-muscarinic therapy, the availability of more than one beta 3-adrenoceptor agonist may prove useful in providing a more patient-centric therapy. Future phase III studies with solabegron will be useful in identifying the potential future role of solabegron in the management of OAB.
References:
- Irwin DE, Abrams P, Milsom I et al. Understanding the elements of overactive bladder: questions raised by the EPIC study. BJU Int 2008; 11: 1381-7.
- Steward WF, Van Rooven JB, Cundigg GW et al. Prevalence and burden of overactive bladder in the United States. World J Urol 2003; 20(6): 327-36.
- Wagg A, Compion G, Fahey A, Siddiqui E. Persistence with prescribed antimuscarinic therapy for overactive bladder. A UK experience. BJU Int 2012; 110: 1767-74.
- Maman K, Aballea S, Nazir J, et al. Comparative efficacy and safety of medical treatments for the management of overactive bladder: a systematic literature review and mixed treatment comparison. Eur Urol 2014; 65: 755-65.
- Hicks A, McCafferty GP, Riedel E, et al. GW427353 (solabegron), a n ovel, selective beta3-adrenergic receptor agonist, evokes bladder relaxation and increases micturition reflex threshold in the dog. J Pharmacol Exp Ther 2007; 323(1): 202-9.
- Ohlstein EH, von Keitz A, Michel MC. A multicenter, double-blind, randomized, placebo-controlled trial of the beta 3-adrenoceptor agonist solabegron for overactive bladder. Eur Urol 2013; 62(5): 834-40.
Written by:
Pamela I. Ellsworth, MD, FACS as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
UMassMemorial Medical Center, Department of Urology, Worcester, MA USA