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 co-primary OAB endpoints of change from baseline at week 12 in average number of daily micturitions and urgency urinary incontinence (UUI) episodes (p<0.001 for each) and key secondary endpoints vs placebo; tolterodine extended-release 4 mg was active control. Treatment was well-tolerated, with a favorable safety profile. 

Presented here are results from the 40-week EMPOWUR extension study for change from EMPOWUR baseline to week 52 for quality-of-life (QOL) endpoints as measured by the Overactive Bladder Questionnaire Long Form (OAB-q LF) and for responder efficacy endpoints of ≥75% and 100% reduction from EMPOWUR baseline in UUI episodes and ≥50% reduction from baseline to week 52 in total incontinence episodes.

The EMPOWUR trial enrolled adults aged ≥18 years who had OAB wet (with incontinence) or OAB dry. The planned enrollment for the extension was approximately 500 men and women who had completed the EMPOWUR trial. Those patients who received vibegron or tolterodine in the EMPOWUR trial continued that treatment in the extension. EMPOWUR patients who received placebo were randomized 1:1 to vibegron or tolterodine; the randomization was stratified by OAB type and sex. The primary objective of the extension was to evaluate vibegron safety and tolerability for up to 52 weeks. Safety assessments were summarized for all patients enrolled in the extension study using descriptive statistics. Secondary efficacy endpoints at week 52 were change from baseline for number of daily micturitions and UUI, urgency, and total incontinence episodes (not presented here). Of 23 exploratory efficacy endpoints, the following nine are presented here: change from baseline at week 52 for all OAB-q LF endpoints (Coping, Health-Related Quality of Life [HRQL], Symptom Bother, Concern, Sleep, and Social Interaction scores) and percentages of OAB wet patients at week 52 with ≥75% and 100% reduction from baseline in UUI episodes and ≥50% reduction in total incontinence episodes.

Quality-of-life efficacy endpoints were calculated for all randomized OAB patients receiving double-blind study treatment and having an evaluable change from baseline micturition measurement in the extension study. The validated OAB-q LF was administered to assess QOL endpoints, for a 1-week recall period, at weeks 12, 24, and 52 relative to start of treatment in the double-blind EMPOWUR trial. The OAB-q LF includes an HRQL scale (25 items) and a Symptom Bother scale (8 items). The HRQL scale includes 4 subscales: Coping, Concern, Sleep, and Social Interaction. Items on the HRQL scales were scored from 1 to 6, with higher scores indicating better QOL. For the Symptom Bother scale, items were scored from 1 to 6, with higher scores indicating greater symptom severity (ie, lower scores showed more improvement). For OAB-q LF scores, if <50% of the scale items were missing, the scale was retained with the mean scale score of the items present used to impute a score for the missing items. 

The incontinence responder efficacy endpoints were calculated for all OAB wet patients receiving double-blind study treatment and having an evaluable change from baseline UUI measurement in the extension study.

Among the safety set (including those randomized from placebo) of 505 patients in the extension study (n=273, vibegron; n=232, tolterodine), the 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% (171/273) of vibegron and 54.3% (126/232) 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 cardiovascular disease, judged not related to study drug by investigators or sponsor) occurred in the vibegron group. 

For the OAB-q LF scores at EMPOWUR baseline, mean scores were similar across both active treatment groups for all scales. Among patients receiving 52 weeks of active treatment, mean change from baseline in the vibegron group (n=164) was numerically better than in the tolterodine group (n=134) for all OAB-q scales (Figure 1). For the responder efficacy endpoints of reduction from EMPOWUR baseline at week 52, for which the analysis model was used, the vibegron group (N=143) demonstrated a numerically greater proportion of patients achieving the endpoints of reduction of ≥75% and 100% in daily UUI episodes and ≥50% in daily total incontinence episodes than the tolterodine group (N=106; Figure 2).

In the 40-week extension to the 12-week EMPOWUR trial, vibegron 75 mg demonstrated numerically greater QOL improvements from baseline at week 52 for all OAB-q scale scores and for proportions of patients meeting responder endpoints relative to tolterodine. Vibegron had a favorable long-term safety profile.

Vibegron demonstrated a favorable long-term safety profile in patients with OAB in the 52-week results from the EMPOWUR extension study. Vibegron 75 mg once daily demonstrated durable efficacy for QOL and incontinence efficacy endpoints.