Urodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine

Abstract

INTRODUCTION AND OBJECTIVE: Vibegron (VIB) is a novel, oral, once-daily b3-adrenergic receptor agonist being investigated for OAB treatment. In the phase 3 randomized, double-blind, 12-week EMPOWUR trial (N[1518), VIB 75 mg statistically significantly improved primary OAB endpoints of daily micturitions and urge urinary incontinence (UUI) (P<0.001 each) and key secondary endpoints vs placebo; tolterodine (TOL) extended-release 4 mg was active control. VIB tolerability was favorable. Results from the 40week EMPOWUR extension are reported. METHODS: EMPOWUR enrolled adults aged 18 years with OAB wet (incontinence) or dry. The 40-week extension enrolled w500 EMPOWUR completers. Those receiving VIB or TOL in EMPOWUR continued; placebo patients (pts) received VIB or TOL (1:1). The primary endpoint was VIB safety and tolerability. Key efficacy endpoints were changes from EMPOWUR baseline at week 52 in average daily micturitions, UUI, urgency, and total urinary incontinence (TUI). RESULTS: Among 505 randomized, treated extension pts (n [273, VIB; n[232, TOL), mean age was 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 (VIB, 85.8%; TOL, 84.1%) were similar. AEs occurred in 62.6% of VIB and 54.3% of TOL pts; 4 (1.5%) VIB and 8 (3.4%) TOL pts discontinued study medication due to an AE. Key AEs (>5% for VIB) for VIB and TOL, 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 VIB group. Among pts receiving 52 weeks of active treatment, there was further improvement from week 12 to 52 in all key OAB endpoints: micturitions and UUI episodes (Figure), urgency (-3.4, VIB [n[176]; -3.2, TOL [n[136]), and TUI (-2.5, VIB [n[143]; -1.9, TOL [n[106]); 61% of VIB-treated pts had a 75% reduction in UUI, and 41% had a 100% reduction (ie, were dry) at week 52. CONCLUSIONS: Consistent with the placebo-controlled EMPOWUR phase 3 study, vibegron demonstrated a favorable longterm safety profile in pts with OAB. Vibegron-treated pts had further improvement in micturitions, UUI, urgency, TUI; 41% with no UUI episodes at week 52. Source of Funding: Urovant Sciences