Efficacy and Safety of Once-Daily Vibegron for Treatment of Overactive Bladder in Patients Aged ≥65 and ≥75 Years: Subpopulation Analysis from the EMPOWUR Randomized, International, Phase III Study

Abstract

Background: Overactive bladder (OAB) is common among older adults. The efficacy and safety of vibegron for the treatment of OAB were demonstrated in the international, phase III EMPOWUR trial. This subpopulation analysis from EMPOWUR assessed the efficacy and safety of vibegron in patients aged ≥ 65 and ≥ 75 years.

Methods: In EMPOWUR, patients with OAB were randomly assigned 5:5:4 to receive once-daily vibegron 75 mg, placebo, or tolterodine 4 mg extended release, respectively, once daily for 12 weeks. Coprimary efficacy endpoints were change from baseline at week 12 in average daily number of micturitions and urge urinary incontinence (UUI) episodes; a key secondary efficacy endpoint was change from baseline at week 12 in average daily number of urgency episodes. Safety was assessed through adverse events (AEs). Efficacy analyses compared vibegron with placebo; no efficacy comparisons were made between vibegron and tolterodine.

Results: Of the 1463 patients with evaluable efficacy data, 628 patients were aged ≥ 65 years, and 179 were aged ≥ 75 years. After 12 weeks, patients treated with once-daily vibegron 75 mg in both age subgroups showed significant improvements from baseline versus placebo in all three symptoms of OAB: daily micturitions (≥ 65 years, P < 0.0001; ≥75 years, P < 0.05), UUI episodes (≥ 65 years, P < 0.001; ≥ 75 years, P < 0.0001), and urgency episodes (≥ 65 years, P < 0.01; ≥ 75 years, P < 0.01). Significant reductions from baseline versus placebo in daily micturitions, UUI episodes, and urgency episodes were observed beginning at week 2 for patients aged ≥ 65 years treated with vibegron. In patients aged ≥ 65 years, 50.0% of those receiving vibegron versus 29.8% receiving placebo experienced a ≥ 75% reduction in UUI episodes at week 12 (P < 0.0001). Rates of cardiovascular-associated AEs were low for patients receiving vibegron (<2% of patients in either age subgroup) and similar to rates in patients receiving placebo. In patients aged ≥ 65 years, hypertension was reported by 1.2%, 3.1%, and 2.9% of patients receiving vibegron, placebo, and tolterodine, respectively; in patients aged ≥ 75 years, hypertension was reported by 1.3%, 3.3%, and 2.1%, respectively.

Conclusions: In this subpopulation analysis of patients with OAB aged ≥ 65 and ≥ 75 years from the EMPOWUR study, once-daily vibegron 75 mg showed rapid onset and robust efficacy versus placebo and was generally safe and well tolerated, consistent with results from the overall population.

Trial registration: ClinicalTrials.gov identifier NCT03492281; registered April 10, 2018.

Conflict of interest statement

S. Varano is principal investigator for Clinical Research Consulting and adjunct professor at Sacred Heart University and University of Bridgeport. D. Staskin is an investigator and consultant for Urovant Sciences; a consultant, investigator, and speaker for Astellas Pharma; and a consultant for New Uro B.V. J. Frankel is an investigator for Urovant Sciences, an investigator and speaker for Astellas Pharma and Pfizer Inc., and a speaker for Tolmar Inc. D. Shortino, R. Jankowich, and P.N. Mudd Jr are employees of Urovant Sciences and may be shareholders.

Figures

Fig. 1

Patient disposition for patients (a) ≥ 65 years and (b) ≥ 75 years. ER extended release, FAS full analysis set, PI principal investigator

Fig. 1

Patient disposition for patients (a) ≥ 65 years and (b) ≥ 75 years. ER extended release, FAS full analysis set, PI principal investigator

Fig. 2

Change from baseline in average daily number of micturitions for patients aged (a) ≥ 65 years and (b) ≥ 75 years in the full analysis set. ER extended release, LS least squares, SE standard error. *P < 0.05, **P < 0.01, ***P < 0.001 vs. placebo using mixed model for repeated measures

Fig. 3

Change from baseline in average daily number of urge urinary incontinence episodes for patients aged a ≥ 65 years and b ≥ 75 years in the full analysis set for incontinence. ER extended release, LS least squares, SE standard error. *P < 0.05, **P < 0.01, ***P < 0.001 vs. placebo using mixed model for repeated measures

Fig. 4

Change from baseline in average daily urgency episodes for patients aged a ≥ 65 years and b ≥ 75 years in the full analysis set. LS least squares, SE standard error. *P < 0.05, **P < 0.01, ***P < 0.001 vs. placebo using mixed model for repeated measures