The approval was based on the phase 3 EMPOWUR trial.
The FDA has approved vibegron (Gemtesa) for the treatment of adult patients with overactive bladder (OAB) with symptoms of urge urinary incontinence (UUI), urgency, and urinary frequency.1
The approval was based on the phase 3 EMPOWUR trial. In the primary study 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).2 The mean change from baseline in UUI episodes was -2.0, -1.4, and -1.8, respectively.
Treatment with vibegron also led to a statistically significant improvement in the key secondary outcome measures of number of urgency episodes, volume per micturition, and proportion of incontinent patients with a ≥75% reduction in urge incontinence episodes (P <.01 for all).
"The clinical data for once-daily 75 mg Gemtesa demonstrated clear efficacy on the key symptoms of OAB by reducing urinary frequency, urge urinary incontinence, and urgency. In addition, data specifically showing reduction in urgency episodes are included in the Prescribing Information of Gemtesa, which is unique among currently-available OAB treatments. Urgency episode reduction data are particularly relevant for OAB patients and their health care providers, as they show Gemtesa’s direct impact on a hallmark symptom of the condition," Cornelia Haag-Molkenteller, MD, PhD, chief medical officer of Urovant Sciences, the manufacturer of vibegron, stated in a press release.1 "By successfully treating clinical symptoms, Gemtesa may allow patients to overcome the devastating impact that OAB can have on their daily lives.
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.
Regarding safety, adverse events (AEs) led to treatment discontinuation in 1.7%, 1.1%, and 3.3%, of the vibegron, placebo, and tolterodine arms, respectively.
Vibegron continued to demonstrate improved clinical outcomes versus tolterodine in results of an extension study of the phase 3 EMPOWUR trial presented during the 2020 International Continence Society online meeting.3
The extension results showed that at week 52, 61% of patients receiving vibegron had a 75% or higher reduction in 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
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.
In the extension, 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%). 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.
"Gemtesa is the first beta 3-agonist available as a once-daily pill which does not require dose titration," said David Staskin, MD, EMPOWUR trial investigator and a leading urologist with St. Elizabeth’s Medical Center in Boston, stated in the press release.1 "Notably, Gemtesa did not have any increase in the adverse event of hypertension compared to placebo in the key EMPOWUR study and has no interactions with medications metabolized by CYP2D6, which is important since many common medications are metabolized by CYP2D6."
1. Urovant Sciences Announces U.S. FDA Approval of GEMTESA® (vibegron) 75 mg Tablets for the Treatment of Patients with Overactive Bladder (OAB). Published online December 23, 2020. https://bit.ly/37I8SVc. Accessed December 23, 2020.
2. 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. J Urol. 2020;204(2):316-324. doi: 10.1097/JU.0000000000000807
3. 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.