Vibegron reduces micturitions, urge incontinence in patients with overactive bladder

Treatment with vibegron 75 mg once daily effectively lowers micturitions, urgency episodes, and urge incontinence and increases the volume per micturition in patients with symptoms of overactive bladder (OAB), results of an international phase III study have shown. It is also safe and well tolerated.

“Statistically significant efficacy began by week 2 and was maintained through week 12,” the researchers said. “Vibegron was generally safe with adverse event (AE) rates comparable with those for placebo, including the incidence of hypertension.”

A total of 1,518 adult patients with OAB with ≥8.0 micturitions per day were randomly assigned 5:5:4 to 75-mg vibegron, placebo, or 4-mg extended-release tolterodine. Up to 25 percent of patients had dry OAB, defined as <1.0 urge incontinence episode per day. Seven-day diaries were completed by participants at baseline and weeks 2, 4, 8, and 12.

Of the randomized patients, 90.4 percent completed the trial. Micturitions decreased by an adjusted mean of 1.8 episodes per day for vibegron compared with 1.3 for placebo (p<0.001) and 1.6 for tolterodine at week 12. Among incontinent patients, urge incontinence episodes decreased by an adjusted mean of 2.0 episodes per day for vibegron compared with 1.4 for placebo (p<0.0001) and 1.8 for tolterodine. [J Urol 2020;204:316-324]

Vibegron was also statistically significantly superior to placebo in terms of number of urgency episodes, volume per micturition, and proportion of incontinent patients with a ≥75-percent reduction in urge incontinence episodes (p_all<0.01).

“In patients treated with 75-mg vibegron once daily, statistically significant reductions compared with placebo were identified in the number of micturitions and number of urge urinary incontinence episodes per day, already observed at week 2 and continuing throughout the rest of the 12-week treatment period,” the researchers said, adding that improvement was consistently higher for vibegron than for tolterodine in all outcome measures.

However, 1.7 percent of patients who received vibegron discontinued treatment due to adverse events (AEs). For placebo and tolterodine, the rates of treatment cessation were 1.1 percent and 3.3 percent, respectively. Hypertension rates were similar at 1.7 percent for vibegron and placebo.

Among AEs of clinical interest, the rates of hypertension, increased blood pressure, urinary tract infection, and urinary retention were similar between vibegron and placebo. No incidence of tachycardia was reported, and dry mouth was less frequent with vibegron than with tolterodine.

“In OAB treatment guidelines intended to maximize symptom control and quality of life and minimize AEs and patient burden, the American Urological Association recommends behavioural therapy as first-line treatment and oral pharmacotherapy with a β₃-adrenoceptor agonist or anticholinergic as second-line treatment,” the researchers noted. [J Urol 2015;193:1572-1580; J Urol 2019;202:558-563]

The current study was limited by its relative short duration, which could be extended from 12 weeks to 52 weeks, according to the researchers. Previous studies of vibegron included 52-week extensions, and open-label treatment was found to deliver a good safety and tolerability profile. [J Urol 2018;199:e970-e971; Int J Urol 2018;25:668-675]