Vibegron for the Treatment of Patients with Dry and Wet Overactive Bladder: A Subgroup Analysis from the EMPOWUR Trial.

Background: Overactive bladder (OAB) is characterized by urgency and frequency with (OAB wet) or without (OAB dry) urge urinary incontinence (UUI). In the phase 3 EMPOWUR trial, vibegron-a selective ß 3-adrenergic receptor agonist for the treatment of OAB-significantly improved daily number of urgency episodes and micturitions vs. placebo (P < 0.01). These post hoc analyses aimed to compare the efficacy of vibegron vs. placebo in OAB dry and wet populations. Methods: Patients were randomly assigned 5:5:4 to receive once-daily vibegron 75 mg, placebo, or tolterodine 4 mg extended release, respectively, for 12 weeks. Baseline criteria for OAB dry included an average of ≥8 micturitions, ≥3 urgency episodes, and <1 UUI episode per diary day and for OAB wet included an average of ≥8 micturitions and ≥1 UUI episode per diary day. Change from baseline in mean daily number of urgency episodes and micturitions was assessed in both populations. Results: Of the 1463 patients included in the full analysis set, 336 (23%) had OAB dry (vibegron, N = 123; placebo, N = 115; and tolterodine, N = 98), and 1127 (77%) had OAB wet (vibegron, N = 403; placebo, N = 405; and tolterodine, N = 319). Vibegron was associated with significant reductions (95% CIs of the least squares mean differences [LSMD] does not include 0) from baseline at week 12 vs. placebo in mean daily urgency episodes for the dry (LSMD [95% CI], ‒1.0 [‒2.0, ‒0.1]) and wet (‒0.6 [‒1.0, ‒0.1]) populations. Vibegron was associated with significant reductions from baseline at week 12 vs. placebo in mean daily micturitions for the dry (LSMD [95% CI], ‒0.8 [‒1.5, ‒ 0.1]) and wet (‒0.5 [‒0.8, ‒0.1]) populations. There were no significant differences in either outcome between tolterodine and placebo for either the dry or wet populations in this study. Conclusions: In this subgroup analysis from the EMPOWUR trial, vibegron was associated with significant reductions compared with placebo in urgency episodes and micturitions in both the OAB dry and wet populations, suggesting that vibegron is similarly efficacious for these endpoints in patients with and without UUI. This trial is registered with NCT03492281.

An Evaluation of the Efficacy and Safety of Vibegron in the Treatment of Overactive Bladder.

Pharmacologic treatment for overactive bladder (OAB), which is characterized by bothersome symptoms such as urgency and urge urinary incontinence (UUI), includes anticholinergics and ß3-adrenergic receptor agonists. Anticholinergics are associated with adverse effects including dry mouth, constipation, cognitive impairment, and increased risk of dementia. Therefore, the drug class of ß3-adrenergic receptor agonists may represent an effective, safe treatment option. Vibegron, a ß3-adrenergic receptor agonist, was approved for use in Japan (2018) and the United States (2020). Over the past 3 years, 2 phase 3 trials (EMPOWUR, EMPOWUR extension) have been conducted with once-daily vibegron 75 mg for the treatment of OAB, and additional secondary and subgroup analyses have detailed the efficacy and safety of vibegron. In the international phase 3 EMPOWUR trial, treatment with vibegron was associated with significant improvements compared with placebo in efficacy outcomes of micturition frequency, UUI episodes, urgency episodes, and volume voided as early as week 2 that were sustained throughout the 12-week trial. The 40-week EMPOWUR extension study, following the 12-week treatment period, demonstrated sustained efficacy in patients receiving vibegron for 52 weeks. Treatment with vibegron was also associated with improvements in patient-reported measures of quality of life. Across studies, vibegron was generally safe and well tolerated. A separate, dedicated ambulatory blood pressure monitoring study showed that treatment with vibegron was not associated with clinically meaningful effects on blood pressure or heart rate. Across all studies, vibegron was efficacious, safe, and well tolerated and thus represents a valuable treatment option for patients with OAB. Here, nearly 1 year after US approval, we review the published data on efficacy and safety of vibegron 75 mg for the treatment of OAB.

Interpretation of the Meaningfulness of Symptom Reduction with Vibegron in Patients with Overactive Bladder: Analyses from EMPOWUR.

INTRODUCTION: Reductions in bothersome symptoms of overactive bladder (OAB) demonstrate improvement in clinical trials, but patient perception of meaningfulness of such improvement is lacking. In the 12-week phase 3 EMPOWUR trial, vibegron significantly reduced average daily number of micturitions, urgency episodes, and urge urinary incontinence (UUI) episodes vs placebo (P < 0.01 each). This analysis assessed meaningfulness of reductions in clinical endpoints observed in EMPOWUR using patient perception of improvement. METHODS: An anchor-based approach using Patient Global Impression of Change (PGI-C) applied to phase 2 data allowed predefining phase 3 responder definitions. To confirm in phase 3, median change from baseline at week 12 in average daily number of micturitions, urgency episodes, and UUI episodes was generated for each PGI-C category and pooled across treatments. Based on predefined meaningful responder definitions, percentages of patients achieving ≥ 15% reduction in micturitions (post hoc), ≥ 50% reduction in urgency episodes (predefined), and ≥ 75% (predefined) and ≥ 90% (post hoc) reduction in UUI episodes were determined for patients receiving vibegron or placebo. RESULTS: Across treatments, for micturitions, urgency episodes, and UUI episodes, median change from baseline to week 12 increased with greater subjective improvement based on PGI-C scores, and median reductions pooled across treatment groups were higher than the responder definitions that patients perceived as improved. Significantly more patients receiving vibegron vs placebo achieved ≥ 15% reduction in micturitions (56.3% vs 44.6%, respectively), ≥ 50% reduction in urgency episodes (39.5% vs 32.8%), ≥ 75% reduction in UUI episodes (49.3% vs 32.8%), and ≥ 90% reduction in UUI episodes (35.2% vs 23.5%) at week 12 (P < 0.05 each). CONCLUSION: Significantly more patients treated with vibegron vs placebo in EMPOWUR achieved meaningful reductions in micturitions, urgency episodes, and UUI episodes that were associated with patient-perceived improvement. Results of these analyses support the meaningfulness of reductions in clinical endpoints observed in the 12-week EMPOWUR trial. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier, NCT03492281.