Investigational medication shows encouraging efficacy in stress urinary incontinence

The investigational noradrenaline reuptake inhibitor TAS-303 demonstrated superior efficacy over placebo with a favorable safety profile in patients with stress urinary incontinence (SUI), according to data from a phase 2 study (NCT04512053) recently published in the Journal of Urology.¹

"Our study adds new evidence that TAS-303 reduces the frequency of incontinence episodes in women with SUI, without the worrisome adverse effects associated with the existing SUI medication duloxetine," says Momokazu Gotoh, MD, PhD.

"Our study adds new evidence that TAS-303 reduces the frequency of incontinence episodes in women with SUI, without the worrisome adverse effects associated with the existing SUI medication duloxetine," said senior author Momokazu Gotoh, MD, PhD, of Chukyo Hospital in Nagoya, Japan, in a news release on the findings.²

Duloxetine is currently approved for the treatment of patients with SUI in Europe. However, the therapy is not approved in the US or Japan because it was determined that the risks of the medication outweighed its benefits, according to the authors.¹

They noted, “However, additional treatment options with fewer safety concerns are needed for patients with SUI.”¹

In total, the current phase 2 trial enrolled 231 female patients with SUI who were randomly assigned 1:1 to receive 18 mg oral TAS-303 once daily (n = 116) or to placebo (n = 115) for 12 weeks.

At 12-week follow-up, TAS-303 demonstrated a least squares mean percent change in SUI episode frequency per 24 hours (SUIEF) of -57.7% (95% CI, −64.9% to –50.6%) vs -46.9% (95% CI, −54.0% to –39.8%)with placebo in the per protocol set. This translated to a least squares mean difference of -10.8% (P = .036). The improvement in percent SUIEF was greater in patients who had 2 or more SUI episodes daily at baseline (59.3% vs 40.5%; P = .006) and in patients with pure SUI (P = .014). An improvement in SUIEF was seen in both patients younger than 60 and in those aged 60 and older.

In the full analysis set, 64.7% of patients in the TAS-303 arm experienced at least a 50% reduction in SUIEF at 12 weeks compared with 53.0% in the placebo arm. TAS-303 also showed improved incontinence episode frequency, incontinence amount, and health-related quality of life at 12 weeks vs placebo, although the differences did not reach statistical significance.

Regarding safety, 29.3% of patients in the TAS-303 arm and 29.6% of patients in the placebo arm experienced any adverse event (AE) during the study period. All AEs were mild or moderate. No severe AEs, serious AEs, discontinuations due to AEs, or nervous system- or gastrointestinal-related AEs were reported.

The double-blind, phase 2 trial enrolled adult Japanese women with SUI across 25 clinical trial sites in Japan. Patients were enrolled between September 4, 2020 and December 22, 2021. The mean age of patients was 53.9 (SD, 8.8) in the TAS-303 arm and 54.1 (SD, 9.3) in the placebo arm.

Patients were eligible for inclusion in the study If they had symptoms of SUI for at least 12 weeks prior to study entry, urinary incontinence per 1-hour pad weight test that exceeded 2.0 g, at least 1 SUI episode per day, an average of 0.43 or less urge urinary incontinence episodes per day, an average of 10 or less urinary diurnal frequency, and an average of 2 or less nocturia frequency per day. Additionally, the number of SUI episodes experienced by patients needed to exceed the number of other episodes.³

The primary outcome measure for the study was the percent change in SUIEF from baseline to week 12 in the per-protocol set. Secondary end points included the proportion of patients with at least a 50% reduction in mean SUIEF, incontinence episode frequency, incontinence amount, health-related quality of life, and safety in the full analysis set.

Overall, the authors concluded, “Based on these findings, TAS-303 may be considered to have comparable efficacy with that of duloxetine (which is marketed in Europe) and improved safety due to the absence of nervous system– or gastrointestinal-related (eg, nausea or vomiting) [adverse drug reactions]. Further validation studies in larger more diverse populations are needed to confirm the efficacy and safety of TAS-303 in women with SUI.”¹

References

1. Takahashi S, Kato K, Yokoyama O, Takei M, Gotoh M. Efficacy and safety of TAS-303 in female patients with stress urinary incontinence: A phase 2, randomized, double-blind, placebo-controlled trial. J Urol. 2024;212(2):267-279. doi:10.1097/JU.0000000000004024

2. New medication for stress urinary incontinence? Investigational drug shows promise. News release. Wolters Kluwer Health: Lippincott. July 11, 2024. Accessed July 12, 2024. https://www.newswise.com/articles/new-medication-for-stress-urinary-incontinence-investigational-drug-shows-promise

3. A phase 2 study of TAS-303 in female patients with stress urinary incontinence. ClinicalTrials.gov. Last updated February 10, 2022. Accessed July 12, 2024. https://clinicaltrials.gov/study/NCT04512053