Efficacy and Safety of Vibegron for the Treatment of Overactive Bladder in Women: A Subgroup Analysis From the Double-Blind, Randomized, Controlled EMPOWUR Trial

Abstract

ABSTRACT The sudden, intense urge to urinate, with or without urge urinary incontinence (UUI), is the predominant characterization of overactive bladder (OAB). Despite a similar prevalence of OAB between both women and men (respectively 17% and 16%), the disproportionate effects of the most bothersome symptoms of UUI fall to women. In addition, OAB’s prevalence in women increases with age when compared with men, leading to decreased scores in quality of life (QoL) measures, sexual function, depression, and sleep quality. Although behavioral therapies such as bladder training and pelvic floor muscle exercises are recommended as the first-line treatment of OAB symptom management, other treatments do exist. These second-line treatments, such as anticholinergics, are commonly prescribed as treatment for these conditions, but their use also entails persistence-limiting adverse effects. Such adverse effects include risk of dementia and cognitive impairment. The American Urogynecologic Society recommends alternative medication consideration for all patients and outright avoidance of anticholinergics for OAB treatment in women older than 70 years. Vibegron, a selective b3-adrenergic receptor agonist, was approved in 2020 for adult OAB treatment. The EMPOWUR trial, the international, placebo- and active-controlled, randomized, double-blind, phase 3 trial, demonstrated over the course of 12 weeks both the efficacy and safety of both vibegron and tolterodine for adults with OAB. Based on the disproportionate nature and bother of OAB symptoms in women, this study intended to analyze subgroups of the EMPOWUR trial to compare the QoL outcomes, 12-week treatment safety, and efficacy of vibegron treatment in women. End points for coprimary efficacy were altered from baseline at week 12 in mean daily number of UUI episodes and micturitions. Secondary efficacy end points included daily number of urgency episodes (also week 12). Exploratory outcomes included change from baseline at weeks 2, 4, and 8 for the same factors. The full set analysis for this study included all women (randomized) receiving greater than 1 dose of vibegron or placebo who experienced greater than 1 measured change using baseline valuations of urgency episodes, micturitions, and QoL outcomes unrelated to incontinence. A total of 1515 patients were included in the safety set, 1289 (84.9%) of which were women (placebo, n = 459; vibegron, n = 463; tolterodine, n = 364), with the mean age being 59.5 years. The study determined that vibegron was associated with a statistically significant greater reduction among women from baseline at week 12 in comparison to placebo. QoL also improved significantly across the board, including total, concern, sleep, coping, and symptom bother subscale scores compared with placebo. Treatment emergent adverse effects incidence was 39.3% with vibegron, 34.9% with placebo, and 39.6% with tolterodine, leading to 1.5%, 1.1%, and 3.8% of women, respectively, discontinuing treatment. The most common treatment emergent adverse effects reported was headache. An analytical limitation was the relatively brief study period of 12 weeks. The double-blind 40-week extension of the EMPOWUR trial (52 total treatment weeks) substantiated long-term safety and efficacy of vibegron (J Urol. 2021;205:1421–1429). Although a relatively high placebo response rate was observed (consistent with other analyses), vibegron was still associated with statistically significant improvements when compared with placebo in OAB symptoms in women. This subgroup analysis of OAB-diagnosed women yielded results consistent with those of the EMPOWUR 12-week trial, which indicated statistically significant reductions versus placebo in efficacy end points with once-daily vibegron 75 mg. The results also showed favorable safety and tolerability profiles. Vibegron treatment among women with OAB also significantly improved measures of QoL versus placebo. All results therefore indicate the efficacy and safety of treatment of women’s OAB with vibegron.