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.

Purpose: We assessed efficacy and safety of URO-902, an investigational gene therapy expressing the α subunit of the large-conductance Ca²⁺-activated K⁺ channel, in a phase 2a placebo-controlled trial in women with overactive bladder (OAB).

Materials and methods: Women, age 40 to 79 years, with OAB and urge urinary incontinence who were refractory to OAB medications were randomized to single-dose URO-902 24 and 48 mg or placebo administered by intradetrusor injection via cystoscopy under local anesthesia. Efficacy end points included change from baseline to week 12 in mean daily micturitions, urgency episodes, urge urinary incontinence episodes, and patient-reported outcomes. Safety assessments included adverse events and postvoid residual urine volume.

Results: Of 80 patients randomized (URO-902 24 mg, n = 26; URO-902 48 mg, n = 27; placebo, n = 27), 74 received treatment, and 67 reached week 24. At week 12, URO-902 24 and 48 mg were associated with significant improvement vs placebo in daily micturitions (least-squares mean change from baseline, -2.3 and -2.4 vs -0.8, respectively; least-squares mean difference [95% CI], ‒1.5 [‒2.7 to ‒0.3] and ‒1.6 [‒2.8 to ‒0.4], nominal P = .017 and P = .009, respectively). URO-902 48 mg was associated with significant improvements vs placebo in urgency episodes (‒3.4 vs ‒1.1; ‒2.2 [‒4.0 to ‒0.4]; nominal P = .016) and percentage of Patient Global Impression of Change responders (58% vs 31%; nominal P = .026). Among patients receiving URO-902 24 mg, URO-902 48 mg, and placebo, 46%, 54%, and 54%, respectively, experienced ≥ 1 treatment-emergent adverse events, most commonly UTI (0%, 15%, 4%) and hematuria (6%, 8%, 8%).

Conclusions: In this phase 2a trial, treatment with URO-902 was associated with improvements vs placebo in efficacy and patient-reported outcomes and was safe and well tolerated.