Once-Daily Vibegron 75 mg for Overactive Bladder (OAB): Double-Blind 52-Week Results From an Extension Study of the International Phase 3 Trial (EMPOWUR)
David Staskin, MD1, Jeffrey Frankel, MD2, Susann Varano, MD3, Denise Shortino, MS4, Rachael Jankowich, RN, MSN4, Paul N Mudd, Jr., PharmD, MBA4.
1Tufts University School of Medicine, Boston, MA, 2Seattle Urology Research Center, Seattle, WA, 3Clinical Research Consulting, Milford, CT, 4Urovant Sciences, Irvine, CA.
Introduction Vibegron is a novel, 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 primary OAB endpoints of daily micturitions and urge urinary incontinence (UUI) (p<0.001 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 are reported.
Materials & Methods EMPOWUR enrolled adults aged ≥18 years with OAB wet (incontinence) or dry. The 40-week extension enrolled ~500 EMPOWUR completers. Those receiving vibegron or tolterodine in EMPOWUR continued; placebo patients received vibegron or tolterodine (1:1). The randomization was stratified by OAB type and sex. The primary endpoint was vibegron safety and tolerability. Key efficacy endpoints were changes from EMPOWUR baseline at week 52 in average daily micturitions, UUI, urgency, and total incontinence.
Results Among 505 randomized, treated extension patients (n=273, vibegron; n=232, tolterodine), 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 62.6% of vibegron and 54.3% of 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 EMPOWUR vibegron and tolterodine patients receiving 52 weeks of active treatment, there was adjusted mean change from EMPOWUR baseline improvement at week 52 in all key OAB endpoints: micturitions (-2.4, vibegron [n=152]; -2.0, tolterodine [n=120]; Figure 1), UUI (-2.2, vibegron [n=125]; -1.7, tolterodine [n=91]; Figure 1), urgency (-3.4, vibegron [n=152]; ‑3.2, tolterodine [n=120]), and total incontinence (-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.Conclusions Consistent with the placebo-controlled EMPOWUR phase 3 study, 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.
Figure legend: Change from baseline least squares mean; 52-week groups only. Covariates included in the mixed model for repeated measures are study visit, treatment, treatment by study visit interaction, baseline, OAB type (micturitions only), and sex. Baseline value is computed using the run-in diary from the EMPOWUR 12-week study. LS, least square; UUI, urge urinary incontinence.
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