Efficacy and Safety of Vibegron for the Treatment of Overactive Bladder in Women: A Subgroup Analysis From the Double-Blind, Randomized, Controlled EMPOWUR Trial

Abstract

Importance The international phase 3 EMPOWUR trial demonstrated efficacy and safety of vibegron, a newer b 3 -adrenergic receptor agonist, in adults with overactive bladder (OAB). Women are disproportionately affected by OAB, especially those with bothersome symptoms, such as urge urinary incontinence (UUI). Objective This subgroup analysis from EMPOWUR assessed efficacy and safety of vibegron in women. Study Design In EMPOWUR, patients with OAB were randomized 5:5:4 to 12 weeks of treatment with once-daily vibegron 75 mg, placebo, or tolterodine 4-mg extended release. Efficacy end points included change from baseline at week 12 in mean daily number of micturitions, UUI episodes, and urgency episodes. Safety was assessed through adverse events (AEs). Results Of the patients included in the analysis, 1286 (84.9%) were women (vibegron, n = 463; placebo, n = 459; tolterodine, n = 364). At week 12, women receiving vibegron showed significant reductions (95% confidence intervals of least squares mean differences does not include 0) from baseline versus placebo in mean daily micturitions, UUI episodes, and urgency episodes, with least squares mean differences (95% confidence intervals) of −0.5 (−0.8 to −0.2), −0.7 (−1.0 to −0.4), and −0.8 (−1.3 to −0.4), respectively. Treatment-emergent AE incidence was similar with vibegron (39%) and placebo (35%); the most common AE with incidence higher with vibegron (4.3%) than placebo (2.6%) was headache. Conclusions In this subgroup analysis, women receiving vibegron showed significant reductions in key efficacy end points versus placebo and favorable safety profile, consistent with the overall results from EMPOWUR, suggesting that vibegron is efficacious and safe for the treatment of OAB in this patient population.

A Comparison of U.S. Individual and Family Plan Medication Coverage for Overactive Bladder

“…A recent systematic review by Yeowell et al 8 found that treatment with mirabegron was associated with greater adherence and longer time to discontinuation compared with anticholinergics with use of ER formulations also noted to be associated with greater adherence. Given the more recent U.S. Food and Drug Administration approval for vibegron, data regarding continuation rates are limited; however, these likely mirror those of mirabegron given its documented tolerability 21,22 . In this context, the finding that beta-agonists are associated with the worst coverage is concerning as it creates a significant obstacle to initiation and continued use of an effective and safe medication therapy for OAB.…”

“…Given the more recent U.S. Food and Drug Administration approval for vibegron, data regarding continuation rates are limited; however, these likely mirror those of mirabegron given its documented tolerability. 21,22 In this context, the finding that beta-agonists are associated with the worst coverage is concerning as it creates a significant obstacle to initiation and continued use of an effective and safe medication therapy for OAB. This lack of coverage for preferred medications combined with existing insurance policies requiring medication trials before moving on to alternative therapies result in an increased unnecessary exposure to anticholinergics and cognitive harm.…”

The AUA/SUFU Guideline on the Diagnosis and Treatment of Idiopathic Overactive Bladder

“…The body of evidence supporting the use of antimuscarinic medications and beta-3 (b3) adrenergic agonist oral medications has demonstrated improvement in urgency urinary episodes, voiding episodes, and UUI [8][9][10][11][12][13][14][15][16][17] as compared to placebo. Clinical studies have also demonstrated that OAB agents significantly improve other outcomes of interest, including overall and condition-specific QoL, 10,11,14,[18][19][20] satisfaction with treatment, 9 and work productivity 21 ; however, there is considerable variance in estimated magnitudes of effects, [8][9][10][11][12][13][14][15][16] and given the lack of evidence indicating superiority for either class when evaluating OAB symptoms control, the Panel concluded that the efficacies of antimuscarinic medications and b3-agonists were similar. Furthermore, the Panel felt it was important to note that the observed placebo effect is very strong in some clinical studies.…”

“…Most clinical studies included assessments of efficacy and/or side-effects at 4 weeks and most were able to demonstrate medication effects by that time. [10][11][12][13]16 Assessment after initiating OAB therapy is important to avoid medical "purgatory," in which patients remain in a state of none to minimal improvement or significant side-effects. Those who do not achieve appropriate improvement should be offered change in therapy.…”

“…Most clinical studies included assessments of efficacy and/or side-effects at 4 weeks and most were able to demonstrate medication effects by that time. 10-13,16…”