The FDA is considering an application for vibegron for the treatment of patients with OAB with symptoms of urge urinary incontinence, urgency, and urinary frequency.
Vibegron continued to demonstrate improved clinical outcomes versus tolterodine in patients with overactive bladder (OAB), according to findings from an extension study of the phase 3 EMPOWUR trial presented during the 2020 International Continence Society (ICS) online meeting.1
The extension results showed that at week 52, 61% of patients receiving vibegron had a 75% or higher reduction in urge urinary incontinence (UUI) episodes compared with 54.5% of patients who received tolterodine. Additionally, 40.8% versus 34.2% of patients, respectively, had a 100% reduction in UUI episodes and experienced no incontinence episodes over a 7-day diary.
Based on the previously reported primary results from the EMPOWUR trial, the FDA is currently reviewing a new drug application (NDA) for vibegron for the treatment of patients with OAB with symptoms of UUI, urgency, and urinary frequency. The FDA action date for the NDA is December 26, 2020.
David Staskin, MD
“A large segment of the OAB population suffers in silence because they are embarrassed, afraid, or unaware that there are treatments, including medications, that could address their problems with bladder control. This situation leads to OAB being overlooked and undertreated, and highlights the need for therapeutic options to improve quality of life,” David Staskin, MD, principal investigator of the EMPOWUR study, leading urologist with St. Elizabeth’s Medical Center, and associate professor of urology at Tufts University School of Medicine, stated in a press release.2
“The EMPOWUR 40-week extension study demonstrated how vibegron, if approved by the FDA, has the potential to offer a lasting solution for adult patients with OAB to manage urinary frequency and urinary incontinence associated with the urgent need to go to the bathroom,” added Staskin.
Vibegron is an investigational, highly selective oral β3‐adrenoreceptor agonist that does not inhibit the CYP2D6 enzyme pathway. The overall EMPOWUR trial included 1518 adult patients with OAB who were assigned in a 5:5:4 ratio to vibegron (75 mg once daily), placebo, or tolterodine.
In the primary analysis, “Vibegron significantly improved the coprimary endpoints of change from baseline in daily micturitions and UUI episodes (P <.001 each) and all key secondary end points versus placebo,” said Staskin when presenting the results during the ICS meeting.
Patients who completed their 12-week treatment course from the primary EMPOWUR analysis were eligible for a 40-week, double-blind extension phase. In the extension, patients continued to receive their active medication from the previous 12 weeks, or if they were initially randomized to placebo, they were randomized in a 1:1 ratio to vibegron or tolterodine.
Of the 587 patients who completed their initial EMPOWUR regimen, 506 chose to participate in the extension study. The mean age of these patients was 61 years, 78% were women, and 78% had OAB wet.
Overall, 183 of the 506 patients had been assigned to placebo, and were thus randomized in the extension to either 40 weeks of vibegron (92 patients) or 40 weeks of tolterodine (91 patients). Of these patients, 85.9% and 79.1%, respectively, completed their 40-week extension regimen.
Among 182 patients who completed their initial vibegron regimen, 85.7% also completed their additional 40 weeks of vibegron. In the group continuing on tolterodine, 87.2% completed their 40-week extension regimen.
At 52 weeks, vibegron showed a mean change from baseline in the average daily number of micturitions of -2.4 compared with -2.0 with tolterodine. Also at week 52, the mean change from baseline in the average number of UUI episodes was -2.2 versus -1.7, respectively.
Regarding safety, Staskin said, “Consistent with the phase 3 placebo controlled EMPOWUR study, vibegron demonstrated a favorable long-term safety profile in patients with OAB in the 40-week extension.”
In the extension, adverse events (AEs) across all grades were experienced by 62.6% of patients receiving vibegron and 54.3% of patients receiving tolterodine. AE-related treatment discontinuations occurred in 1.5% (4 patients) versus 3.4% (8 patients) of the 2 groups respectively.
"Adverse events of blood pressure elevation were more common in the tolterodine group (1.7%) than in the vibegron group (0.7%),” said Staskin.
There was 1 patient death in the vibegron group, which was due to arteriosclerotic heart disease and not deemed to be related to study treatment.
In the primary EMPOWUR analysis, at 12 weeks, vibegron showed a mean change from baseline in the average daily number of micturitions of -1.8 compared with -1.3 for placebo and -1.6 for tolterodine (P <.001).3 The mean change from baseline in UUI episodes was -2.0, -1.4, and -1.8, respectively.
1. Staskin D, Frankel J, Varano S, et al. Once-daily vibegron 75 mg for overactive bladder: double-blind 52-week results from an extension study of the international phase 3 trial (EMPOWUR). Presented during: 2020 the International Continence Society online meeting. November 19-22, 2020. Poster 33.
2. Urovant Sciences Announces Positive Clinical Efficacy and Safety Data from Vibegron EMPOWUR Long Term Extension Study. Posted online November 19, 2020. https://bit.ly/2HiXXqq. Accessed November 20, 2020.
3. Staskin D, Frankel J, Varano S, et al. International phase III, randomized, double-blind, placebo and active controlled study to evaluate the safety and efficacy of vibegron in patients with symptoms of overactive bladder: EMPOWUR. Clinical Trial J Urol. 2020;204(2):316-324. doi: 10.1097/JU.0000000000000807