Vibegron is a novel, highly selective, oral, once-daily β3-adrenergic receptor agonist being investigated for overactive bladder (OAB) treatment. In the phase 3 randomized, double-blind, 12-week EMPOWUR trial (N=1518), vibegron 75 mg statistically significantly improved co-primary OAB endpoints of change from baseline to week 12 in average daily number of micturitions and urgency urinary incontinence (UUI) episodes (p<0.001 for each) and key secondary endpoints vs placebo; tolterodine extended-release 4 mg was active control. Vibegron tolerability was favorable. Results from the 40-week EMPOWUR extension study are reported.

EMPOWUR enrolled adults aged ≥18 years with OAB wet (with incontinence) or OAB dry. The planned enrollment for the 40-week extension study was 500 patients who had completed the EMPOWUR trial. Those patients who received vibegron or tolterodine in the EMPOWUR trial continued that treatment in the extension study. Patients who received placebo in EMPOWUR were randomized to vibegron or tolterodine (1:1), with the randomization stratified by OAB type and sex. The primary objective of the extension was to evaluate vibegron safety and tolerability for up to 52 weeks. Safety assessments were summarized for all enrolled patients using descriptive statistics. 

Key efficacy endpoints were changes from EMPOWUR baseline at week 52 for average daily micturitions, UUI episodes, urgency episodes, and total incontinence episodes. A mixed model for repeated measures with restricted maximum likelihood estimation was used. The analysis model included treatment, visit, baseline stratification factors, baseline value, and interaction by treatment visit.

Among 505 randomized, treated patients (n=273, vibegron; n=232, tolterodine) in the EMPOWUR extension, median age was 64.0 years (mean age: 61.1 years); 46.5% were aged ≥65 years; 78.2% were women; and 78.2% had OAB wet. Baseline characteristics and extension completion rates (vibegron, 85.8%; tolterodine, 84.1%) were similar. Adverse events (AEs) occurred in 171 (62.6%) vibegron and 126 (54.3%) tolterodine patients; 4 (1.5%) vibegron and 8 (3.4%) tolterodine patients discontinued study medication due to an AE. Key AEs (>5% for vibegron) for vibegron and tolterodine, respectively, were hypertension (8.8% and 8.6%), urinary tract infection (6.6% and 7.3%), and headache (5.5% and 3.9%). One death (due to arteriosclerotic disease, judged not related to study drug by investigators or sponsor) occurred in the vibegron group. 

Among patients receiving active treatment throughout the full 52 weeks of EMPOWUR trial and extension, there was adjusted mean change from EMPOWUR baseline improvement at week 52 in all key OAB endpoints: micturitions (-2.4, vibegron [n=152 for calculation of adjusted mean change]; -2.0, tolterodine [n=120]; Figure 1), UUI episodes (-2.2, vibegron [n=125]; -1.7, tolterodine [n=91]; Figure 1), urgency episodes (-3.4, vibegron [n=152];  3.2, tolterodine [n=120]), and total incontinence episodes (-2.5, vibegron [n=125]; -1.9, tolterodine [n=91]); 61.0% of 143 vibegron-treated patients had a ≥75% reduction in UUI, and 40.8% became dry (100% reduction) at week 52.

Consistent with the placebo-controlled EMPOWUR phase 3 study, vibegron 75 mg demonstrated a favorable long-term safety profile in patients with OAB in the 40-week extension. Vibegron demonstrated durable efficacy across all OAB endpoints.

Vibegron demonstrated a favorable long-term safety profile in extension patients with OAB and showed durable improvements in micturitions, UUI, urgency, and total incontinence; 40.8% of wet patients became dry at week 52.