Once-Daily Vibegron 75 mg for Overactive Bladder: Long-Term Safety and Efficacy from a Double-Blind Extension Study of the International Phase 3 Trial (EMPOWUR)

Abstract

The long-term safety, tolerability and efficacy of vibegron in adults with overactive bladder were evaluated in the 40-week phase 3 EMPOWUR extension study. Materials and Methods: Patients who completed 12 weeks of once-daily vibegron 75 mg or tolterodine 4 mg extended release in EMPOWUR continued double-blind treatment; patients who completed 12 weeks of placebo were randomly assigned 1:1 to receive double-blind vibegron or tolterodine. The primary outcome was safety, measured by incidence of adverse events. Secondary outcomes included change from baseline at week 52 in average daily number of micturitions and urgency episodes (all patients), and urge and total urinary incontinence episodes (patients with overactive bladder wet) based on 7-day diary data. Results: Of 506 patients randomized 505 received !1 dose of medication, and 430 (85%) completed the study. A total of 12 patients (2.4%) discontinued owing to adverse events. The most common adverse events with vibegron/tolterodine (>5% in either group) were hypertension (8.8%/8.6%), urinary tract infection (6.6%/ 7.3%), headache (5.5%/3.9%), nasopharyngitis (4.8%/5.2%) and dry mouth (1.8%/ 5.2%). Improvements in efficacy end points were maintained for patients receiving vibegron for 52 weeks; least squares mean change from baseline to week 52 in micturitions was -2.4 for vibegron vs -2.0 for tolterodine; in urge urinary incontinence episodes -2.2 vs -1.7 (p <0.05); in urgency episodes -3.4 vs -3.2; and in total incontinence episodes -2.5 vs -1.9 (p <0.05). Among patients with overactive bladder wet 61.0% receiving vibegron experienced !75% reduction in urge urinary incontinence episodes after 52 weeks of treatment vs 54.4% with tolterodine, while 40.8% vs 34.2% experienced a 100% reduction.

Efficacy of Vibegron and Mirabegron for Overactive Bladder: A Systematic Literature Review and Indirect Treatment Comparison

“…A manual search of primary publications and references was performed to identify relevant articles not captured during the initial search. Previously unpublished data for two phase 3 studies of vibegron were provided by Urovant Sciences in the form of clinical study reports; data for the trials have since been published [12,13].…”

“…After removal of duplicates, 49 records remained and were screened for inclusion; 34 records did not meet inclusion criteria, resulting in 15 full-text articles being assessed for eligibility. After further evaluation, seven were identified and included in the meta-analyses [18,[21][22][23][24][25][26], in addition to the vibegron phase 3 EMPOWUR [12] and EMPOWUR extension [13] trials.…”

“…Only the publications by Chapple et al [21], Herschorn et al [22], Khullar et al [23], Nitti et al [24], Yamaguchi et al [25], Kuo et al [26], and Staskin et al [13] reported the incidence of AEs that occurred in at least 2% of any treatment group. Staskin et al [12] reported AEs with an incidence of at least 2% in the vibegron group and greater than for placebo.…”

“…Across the long-term trials, the most frequently occurring AE with mirabegron 50 mg, vibegron, and tolterodine was hypertension (9.2%, 8.8%, and 8.6-9.6%, respectively; Supplementary Table 6). Additional AEs reported at an incidence of at least 5% were UTI with mirabegron 50 mg; UTI and headache with vibegron; and UTI, dry mouth, and nasopharyngitis with tolterodine [13,21].…”

“…Monotherapy with a b 3 -adrenergic agonist may be preferred in older patients, those with high anticholinergic burden, and older adults with multiple comorbidities. Vibegron is a selective b 3 -adrenergic agonist that was approved by the US Food and Drug Administration at a once-daily dose of 75 mg for the treatment of OAB [12,13]. Dosage adjustments are not recommended for patients with renal or mild to moderate hepatic impairment [14].…”