Once-Daily Vibegron 75 mg for Overactive Bladder: Long-Term Safety and Efficacy from a Double-Blind Extension Study of the International Phase 3 Trial (EMPOWUR).

PURPOSE: The long-term safety, tolerability and efficacy of vibegron in adults with overactive bladder were evaluated in the 40-week phase 3 EMPOWUR extension study. MATERIALS AND METHODS: Patients who completed 12 weeks of once-daily vibegron 75 mg or tolterodine 4 mg extended release in EMPOWUR continued double-blind treatment; patients who completed 12 weeks of placebo were randomly assigned 1:1 to receive double-blind vibegron or tolterodine. The primary outcome was safety, measured by incidence of adverse events. Secondary outcomes included change from baseline at week 52 in average daily number of micturitions and urgency episodes (all patients), and urge and total urinary incontinence episodes (patients with overactive bladder wet) based on 7-day diary data. RESULTS: Of 506 patients randomized 505 received ≥1 dose of medication, and 430 (85%) completed the study. A total of 12 patients (2.4%) discontinued owing to adverse events. The most common adverse events with vibegron/tolterodine (>5% in either group) were hypertension (8.8%/8.6%), urinary tract infection (6.6%/7.3%), headache (5.5%/3.9%), nasopharyngitis (4.8%/5.2%) and dry mouth (1.8%/5.2%). Improvements in efficacy end points were maintained for patients receiving vibegron for 52 weeks; least squares mean change from baseline to week 52 in micturitions was ‒2.4 for vibegron vs ‒2.0 for tolterodine; in urge urinary incontinence episodes ‒2.2 vs ‒1.7 (p <0.05); in urgency episodes ‒3.4 vs ‒3.2; and in total incontinence episodes ‒2.5 vs ‒1.9 (p <0.05). Among patients with overactive bladder wet 61.0% receiving vibegron experienced ≥75% reduction in urge urinary incontinence episodes after 52 weeks of treatment vs 54.4% with tolterodine, while 40.8% vs 34.2% experienced a 100% reduction. CONCLUSIONS: Vibegron demonstrated favorable long-term safety, tolerability and efficacy in patients with overactive bladder, consistent with results of the 12-week study.

Long-term efficacy and safety of vibegron versus mirabegron and anticholinergics for overactive bladder: a systematic review and network meta-analysis.

Background: Few randomized controlled trials evaluate the long-term efficacy and safety of pharmacotherapy for overactive bladder (OAB). This network meta- analysis compares the long-term (52-week) efficacy and safety of vibegron, mirabegron and anticholinergics for the treatment of OAB. Methods: A systematic literature review and network meta-analysis were conducted following PRISMA guidelines using MEDLINE, Embase and Cochrane Central Register of Controlled Trials and terms related to OAB. Efficacy outcomes included change from baseline to week 48-52 in mean daily total urinary incontinence (UI) episodes, mean daily number of micturitions and volume voided/micturition. Efficacy outcomes were analysed using Bayesian models. Commonly reported adverse events (AEs) are described. Results: Of 2098 hits retrieved, 5 publications and 1 study report describing 5 unique randomized controlled trials were included in the analyses. Mean (95% credible interval) change from baseline in total UI episodes for vibegron 75 mg (-2.2; -2.9 to -1.5) showed a significantly greater reduction than mirabegron 50 mg (-1.3; -1.9 to -0.8) and tolterodine 4 mg extended release (-1.6; -2.1 to -1.1). No significant differences were observed between vibegron and comparators for daily micturitions or volume voided/micturition. Within the manuscripts, the 4 most common AEs (range) for anticholinergics included dry mouth (5.2-90.0%), constipation (7.7-65.0%), blurred vision (3.8-35.0%) and hypertension (8.6-9.6%); the 4 most commonly reported AEs for ß3-adrenergic agonists included hypertension (8.8-9.2%), urinary tract infection (5.9-6.6%), headache (5.5%) and nasopharyngitis (4.8-5.2%). Conclusion: Vibegron was associated with significantly greater improvement in daily total UI episodes at 52 weeks than mirabegron and tolterodine. When reported, the most common AE for anticholinergics was dry mouth and for ß3-adrenergic agonists was hypertension. Hypertension incidence was similar between drug classes.

Efficacy of Vibegron and Mirabegron for Overactive Bladder: A Systematic Literature Review and Indirect Treatment Comparison.

BACKGROUND: In the absence of head-to-head trials, we performed an indirect treatment comparison of the ß3-adrenergic agonists vibegron and mirabegron in the treatment of overactive bladder (OAB). METHODS: PubMed, Embase, and Cochrane Library were searched for articles related to phase 3, double-blind, controlled trials of vibegron 75 mg and mirabegron 25/50 mg in patients with OAB. Efficacy outcomes included change from baseline at weeks 4, 12, and 52 in mean daily number of total urinary incontinence episodes and micturitions and mean volume voided/micturition. Effect size was computed as placebo-subtracted change from baseline (weeks 4, 12) or active control (tolterodine)-subtracted change from baseline (week 52) for each treatment group. Adverse events (AEs) are presented descriptively. RESULTS: After removal of duplicates, 49 records were identified, and after screening 9 met inclusion criteria for analysis. Vibegron showed significantly greater reduction in mean daily number of total incontinence episodes than mirabegron 25 mg at week 4, mirabegron 50 mg (weeks 4, 52), and tolterodine (weeks 4, 12) (P < 0.05, each) and significantly greater improvement in volume voided versus mirabegron 25 mg (week 12), mirabegron 50 mg (weeks 12, 52), and tolterodine (week 4) (P < 0.05, each). Confidence intervals of point estimates overlapped zero for all other comparisons of vibegron and mirabegron (25 or 50 mg) or tolterodine, indicating no significant differences between treatments for these time/endpoints. Urinary tract infection, hypertension, and dry mouth were the most commonly occurring AEs for vibegron, mirabegron, and tolterodine, respectively, in the short-term trials; hypertension was the most commonly occurring AE with all three treatments in the long-term trials. CONCLUSIONS: Vibegron was associated with significant improvement in total incontinence episodes versus mirabegron at 4 and 52 weeks and volume voided at 12 and 52 weeks. Improvement in micturitions was similar between vibegron and mirabegron or tolterodine. Incidence of AEs was generally comparable between vibegron and mirabegron.