Gene therapy shows encouraging efficacy for overactive bladder

The investigational gene therapy URO-902 demonstrated improved efficacy vs placebo while maintaining a manageable safety profile in women with overactive bladder (OAB) and urge urinary incontinence (UUI), according to data from a phase 2a study (NCT04211831) published in the Journal of Urology.¹

“Expanded clinical studies are warranted to further elucidate the efficacy and safety of URO-902," the authors wrote.

According to the authors, URO-902 “consists of a nonviral double-stranded naked DNA plasmid (pVAX vector) containing a complementary DNA insert (hSlo) that expresses the pore-forming α subunit of the human large-conductance Ca2+-activated K+ channel.”

For the study, the investigators enrolled 80 patients with OAB and UUI who were refractory to OAB medications. Participants were recruited across 14 clinical trial sites in the US. Patients included in the study were randomly assigned 1:1:1 to receive URO-902 at a 24 mg dose (n = 26) or a 48 mg dose (n = 27), or placebo (n = 27).

At week 12, patients in the URO-902 cohorts demonstrated significantly greater improvements in daily microuritions compared with those in the placebo arm. Specifically, the change from baseline to 12 weeks was -0.8 in the placebo arm compared with -2.3 in the 24 mg arm (least-squares mean difference, ‒1.5; 95% CI, ‒2.7 to ‒0.3; P = .017) and -2.4 in the 48 mg arm (least squares mean difference, ‒1.6; 95% CI, ‒2.8 to ‒0.4; P = .009).

Patients in the URO-902 48mg dose cohort also demonstrated statistically significant improvements over placebo in the change in daily urgency episodes and percentage of Patient Global Impression of Change (PGI-C) responders. The decrease in urgency episodes from baseline to 12 weeks was 3.4 in the URO-902 arm vs 1.1 in the placebo arm (least squares mean difference, ‒2.2; 95% CI, ‒4.0 to ‒0.4; P = .016). Further, 58% of patients in the URO-902 48 mg arm vs 31% of patients in the placebo arm were considered responders to PGI-C (P = .026).

A numerically greater percentage of patients in the URO-902 cohorts achieved a reduction in UUI episodes vs those in the placebo cohort, though these differences did not reach statistical significance. At week 12, 35% of patients in the placebo arm experienced at least a 50% reduction in UUI episodes from baseline compared with 50% of patients in the URO-902 24 mg arm (P = .12) and 50% of patients in the URO-902 48 mg cohort (P = .17). Similarly, 31% of patients in the placebo arm achieved at least a 75% reduction in UUI episodes from baseline to 12 weeks compared with 41% of patients in the URO-902 24 mg cohort (P = .3) and 38% of patients in the URO-902 48 mg cohort (P = .4).

The authors also reported, “The proportion of participants achieving 100% reduction in UUI episodes was similar with URO-902 24 mg, URO-902 48 mg, and placebo (5% and 8% vs 12%, respectively; P = .6 and P = 1, respectively).”

Patients in the URO-902 48 mg cohort achieved a numerically higher improvement in the Urinary Incontinence‒Specific Quality-of-Life Instrument total summary score at week 12 vs placebo (P = .2). Scores among patients in the URO-902 24 mg cohort and patients in the placebo cohort were comparable (P > .9).

Changes in the OAB Questionnaire (OAB-q) total scores from baseline to 12 weeks was numerically higher in the URO-902 24 mg and 48 mg cohorts vs placebo (P = .3 and P = .091, respectively). Patients in the URO-902 cohorts also achieved significantly improvements in the change of OAB-q symptom bother scores from baseline to 12 weeks vs placebo (P = .043 and P = .025, respectively).

Reragrding safety, URO-902 was found to be well-tolerated. Treatment-emergent adverse events (TEAEs) occurred in 46% of patients in the URO-902 24 mg arm, 54% of patients in the URO-902 48 mg arm, and 54% of patients in the placebo arm. The most common TEAEs were urinary tract infection, which was reported in 0%, 15%, and 4% patients, respectively, and hematuria, which was reported in 6%, 8%, and 8% of patients, respectively.

Serious TEAEs occurred in 5%, 8%, and 12% of patients, respectively.

Based on these findings, the authors concluded, “Expanded clinical studies are warranted to further elucidate the efficacy and safety of URO-902, possibly at higher doses, as a potential safe and durable treatment of refractory OAB.”

REFERENCE

1. Enemchukwu EA, Kalota S, Robertson K, et al. Gene therapy with URO-902 (pVAX/hSlo) for the treatment of female patients with overactive bladder and urge urinary incontinence: Safety and efficacy from a randomized phase 2a trial. J Urol. 2025;213(4):417-427. doi:10.1097/JU.0000000000004373