Reductions in bothersome symptoms of frequent micturitions, urgency episodes, and urge urinary incontinence episodes are generally reported to demonstrate improvement in clinical trials for overactive bladder (OAB), but the interpretation and meaningfulness of the magnitude of the reduction for each symptom is often omitted. In the phase 3 EMPOWUR trial, once-daily vibegron 75 mg was associated with significant improvement from baseline at week 12 in average daily number of micturitions, urgency episodes, and urge urinary incontinence episodes vs placebo (P<0.01, each). These analyses used a classic, anchor-based approach to interpret the meaningfulness of change in micturitions, urgency episodes, and urge urinary incontinence episodes based on the patient global impression of change (PGI-C) and predefined responder definitions.

Median change from baseline at week 12 in average daily number of micturitions, urgency episodes, and urge urinary incontinence episodes was generated for each PGI-C category, pooled across treatment groups. Response options for the PGI-C included much better, moderately better, a little better, no change, a little worse, moderately worse, and much worse. Responses of no change and worse were combined for these analyses. Median changes associated with PGI-C of moderately better and much better were used to define meaningful changes, and the percentages of patients achieving these reductions (≥15% reduction in micturitions and ≥90% reduction in urge urinary incontinence episodes, post hoc analyses; ≥50% reduction in urgency episodes and ≥75% reduction in urge urinary incontinence episodes, predefined in EMPOWUR) were determined. As supportive evidence, patient interviews were conducted to understand the bother associated with symptoms of OAB.

Across treatment groups, patients who experienced greater change from baseline at week 12 in micturitions, urgency episodes, and urge urinary incontinence episodes reported greater improvement in PGI-C (Figure). Patients with ≥15% reduction from baseline in micturitions reported at least moderately better for PGI-C; a significantly greater percentage of patients receiving vibegron (56.3%) vs placebo (44.6%) achieved this ≥15% reduction in micturitions (nominal P=0.0002). Patients with ≥50% reductions from baseline in urgency episodes reported much better for PGI-C; significantly more patients receiving vibegron (39.5%) vs placebo (32.8%) achieved this ≥50% reduction in urgency episodes (P=0.0235). Patients with ≥90% reductions from baseline in urge urinary incontinence episodes reported much better for PGI-C; significantly more patients receiving vibegron (35.2%) vs placebo (23.5%) experienced this ≥90% reduction in urge urinary incontinence episodes (nominal P<0.001), consistent with the significantly greater percentage of vibegron- vs placebo-treated patients experiencing a ≥75% reduction in urge urinary incontinence episodes reported in EMPOWUR (PGI-C of at least moderately better; 49.3% vs 32.8%, respectively).

Significantly more patients treated with vibegron in EMPOWUR achieved meaningful reductions in micturitions, urgency episodes, and urge urinary incontinence episodes that were associated with patient perception of moderate to much improvement compared with placebo at week 12.

The patient perception of change associated with treatment with vibegron supports the clinical meaningfulness of a ≥15% reduction in micturitions, ≥50% reduction in urgency episodes, and ≥90% reduction in urge urinary incontinence episodes. A statistically significantly greater percentage of patients receiving vibegron compared with placebo achieved these clinically meaningful thresholds.