Vibegron provides long-term improvement in urinary symptoms associated with overactive bladder

Long-term safety and efficacy data showed that vibegron is a safe, effective add-on therapy for men with benign prostatic hyperplasia (BPH) who continue to experience overactive bladder (OAB) symptoms despite conventional treatment with alpha-blockers. David Staskin, MD, an associate professor of urology at Tufts University School of Medicine, in Boston, presented new findings from the open-label extension phase of the COURAGE trial at the 2025 Annual Meeting of the American Urological Association in Las Vegas, Nevada.

BPH, a urologic condition characterized by the nonmalignant growth of prostate tissue, is a common cause of lower urinary tract symptoms (LUTS) in older adults. The prevalence of BPH increases with advancing age, affecting up to 60% of men in their 60s, and 80% to 90% of those aged 70 years and older [Roehrborn CG. Rev Urol. 2005;7 Suppl 9:S3-S14.]. A significant portion of men living with this condition experience LUTS consistent with a diagnosis of OAB, such as increased urinary frequency, nocturia, urgency, and urge urinary incontinence. Well-established pharmacologic options for BPH, which include alpha-blockers and 5-alpha reductase inhibitors (5-ARIs), typically fail to achieve improvement or resolution of OAB symptoms in all individuals with BPH [Kaplan SA, et al. JAMA. 2006;296(19):2319-23280]. Beta-3 adrenergic agonists like vibegron have emerged as add-on therapies for BPH to help manage symptoms of OAB that do not respond to first-line therapies.  
In the initial phase 3, randomized, placebo-controlled COURAGE trial, once-daily vibegron (75 mg) achieved significant, clinically meaningful improvements in OAB symptoms over 24 weeks in men treated with first-line pharmacotherapy for OAB, and was generally safe and well tolerated, with adverse event (AE) rates similar to those observed with placebo [Staskin D, et al. J Urol. 2024;212(2):256-266]. Participants in the United States and Poland who completed the 24-week, double-blind, randomized, placebo-controlled COURAGE trial were eligible to enroll in the open-label extension phase. Patients who received vibegron over the initial 24 weeks continued to receive once-daily vibegron (75 mg) for 28 weeks, and those who initially received placebo were switched to once-daily vibegron (75 mg) for 28 weeks in the extension phase. All participants continued to take a stable dose of alpha-blockers, with or without a 5-ARI. In total, 276 participants who completed the COURAGE trial enrolled in the extension phase. Most of the participants (90.6%) completed the extension study.

Vibegron was well tolerated across the cohort, with no additional safety concerns identified with exposure up to 52 weeks. The overall incidence of AEs during the open-label extension phase (29.6%) was similar to the incidence reported during the double-blind treatment period (35.9%). The most commonly reported AEs during open-label treatment were hypertension (6.3%), COVID-19 (5.6%), and increased hepatic enzyme levels (2.1%). Only 7 participants (4.9%) experienced one or more treatment-related AEs during the extension phase. The analysis did not reveal any clinically meaningful changes in laboratory assessments or vital signs.

The efficacy analysis showed that improvements in symptoms were sustained among participants treated with vibegron over 52 weeks, and efficacy outcomes improved after 28 weeks of vibegron treatment for those who received placebo in the initial COURAGE trial. Among participants receiving vibegron for 52 weeks, median International Prostate Symptom Scores decreased from baseline to week 52 (−7.0 [−11.0, −2.0]). Moreover, no participants had post-void residual (PVR) urine volumes ≥200 mL at two or more consecutive assessments.

The authors noted that the lack of a clinically relevant effect on PVR urine volume and the low incidence of urinary retention suggest that vibegron does not increase the risk for urinary retention in this population. “The 24-week initial study included a group who underwent urodynamic studies that demonstrated the drug did not affect bladder contractility during voiding,” Staskin explained. “The flow was not decreased, the residual urine was not clinically significantly increased, and the peak contractile pressure was not decreased. Therefore, it is not surprising that men who were on therapy for 52 weeks should have the same rate of urinary retention as those receiving placebo in the first 24 weeks or as the general population in the following 28 weeks.”

As the emerging data continue to highlight a favorable safety profile and insurance coverage for beta-3 adrenergic agonists becomes more refined across the United States, vibegron uptake will likely continue to increase in urology and primary care practices, Staskin added.