Overactive bladder treatment maintains favorable long-term safety profile

Findings from a double-blind extension study of the vibegron EMPOWUR phase 3 trial demonstrated that once-daily vibegron maintained a favorable safety profile and had durable benefit for improving symptoms of overactive bladder (OAB) over the 52 weeks of the study, exceeding that of the comparator anticholinergic agent, tolterodine extended release.

The data were presented by David Staskin, MD, during the 2020 American Urological Association Virtual Experience.¹

“Long-term efficacy and safety were investigated as key outcome measures in the extension

David Staskin, MD

study, and the long-term safety profile demonstrated for vibegron is consistent with the findings in the 12-week placebo-controlled phase 3 study,” said Staskin, associate professor of urology at Tufts University School of Medicine in Boston, Massachusetts.

“The efficacy data from the extension study showed that the benefits of vibegron for reducing average number of daily micturitions, episodes of urge urinary incontinence [UUI], urgency, and total incontinence that were observed at the end of the 12-week pivotal trial were maintained with treatment for up to 52 weeks,” Staskin said. “Furthermore, in post hoc analyses of data from the extension study, vibegron had statistically significant superiority to tolterodine extended-release for reducing UUI and total incontinence episodes.”

Vibegron is a novel ß3-adrenergic receptor agonist. A once-daily dose of vibegron 75 mg was administered in the EMPOWUR phase 3 study (NCT03492281) and the extension study. Notably, vibegron does not inhibit the cytochrome P450 2D6 enzyme (CYP2D6), the hepatic enzyme that is involved in the metabolism of approximately 25% of all drugs. Approximately 43% of patients with OAB take a drug metabolized by CYP2D6.

“Avoiding the potential for drug interactions is especially important in this population, as many OAB patients have comorbidities and take multiple medications,” Staskin said.

Reductions in average daily micturitions seen

Significant reductions in average daily micturitions were seen at week 2 among those taking vibegron, and there was even greater benefit at week 52 in the extension trial, when the mean change from baseline was –2.4. A similar pattern was observed in the analysis of reduction in UUI episodes over time among patients treated with vibegron.

The analysis of change in daily urgency episodes from baseline to week 52 showed a reduction of 3.4 in the vibegron group and 3.2 for tolterodine. At 52 weeks compared with baseline, patients treated with vibegron had 2.5 fewer incontinence episodes daily; daily episodes were reduced by an average of 1.9 in the tolterodine group.

“Post hoc analyses evaluating the difference in week 52 change from baseline between vibegron and tolterodine using the mixed model for repeated measures specified in the statistical analysis plan showed vibegron was statistically superior to tolterodine for reducing both UUI and total incontinence episodes from baseline to week 52,” Staskin said.

Results of a UUI responder analysis of UUI episodes recorded in a 7-day diary showed that 61% of vibegron-treated patients achieved at least a 75% reduction at week 52 and 41% of patients had a 100% reduction: They were dry with no incontinence episodes over the study’s final 7 days.

The phase 3, 12-week, placebo- and active-controlled, double-blind EMPOWUR study randomized 1518 adults with wet or dry OAB to once-daily treatment with vibegron 75 mg, placebo, or tolterodine extended-release 4 mg. EMPOWUR met both coprimary end points, demonstrating statistically significant greater improvement in average number of daily micturitions and UUI episodes with vibegron compared with placebo.

“There was no preplanned statistical comparison between vibegron and tolterodine in EMPOWUR, but numerical differences favoring vibegron were noted in all evaluable efficacy measures,” Staskin said.

In the double-blind extension study, patients originally randomized to vibegron or tolterodine continued the same treatment, and patients in the placebo group were randomized to receive vibegron or tolterodine. The extension study had a target participation of 500 patients. It enrolled 506 patients, and 505 received at least 1 dose of study medication, including 273 who received vibegron and 232 who got tolterodine. The completion rate of patients in the extension trial was approximately 85% and similar across all treatment groups.

Baseline characteristics of participants in the extension trial were similar to those of the EMPOWUR study. They had a median age of 64 years, 78% were women, and 78% had wet OAB.

Adverse events (AEs) were reported by 62.6% of patients receiving vibegron and 54.3% of patients in the tolterodine group. Rates of AE-related discontinuation in the vibegron and tolterodine groups were 1.5% and 3.4%, respectively; rates of treatment-emergent serious AEs were 3.3% and 4.3%, respectively.

AEs reported by more than 5% of patients treated with vibegron included hypertension (8.8%), urinary tract infection (6.6%), and headache (5.5%). The rates of these AEs, including that of hypertension, were similar in the tolterodine group, Staskin reported.

“First demonstrated in the 12-week EMPOWUR study, data from the extension study now confirm efficacy and a very good safety and tolerability profile for vibegron over the 52 weeks of treatment,” Staskin said.

Disclosures: Urovant Sciences provided funding for the study. Staskin is an investigator and consultant for Urovant Sciences and a consultant to Astellas Pharma, Ferring Pharmaceuticals, and New Uro BV.

Reference

1. Staskin D, Frankel J, Varano S, Shortino D, Jankowich R, Mudd P. Once-daily vibegron 75 mg for overactive bladder (OAB): double-blind 52-week results from an extension study of the international phase 3 trial (EMPOWUR). Paper presented at: 2020 American Urological Association Virtual Experience; June 27-28, 2020.