ICS 2022: Efficacy And Safety Of A Novel Gene Therapy (URO-902; PVAX/HSLO) In Female Patients With Overactive Bladder Syndrome And Urgency Urinary Incontinence: Results From A Phase 2a Trial

(UroToday.com) URO-902 is an intradetrusor injection investigational gene therapy for overactive bladder (OAB). It consists of a plasmid vector that expresses the α subunit of the large-conductance Ca2+-activated K+ channel in the detrusor to reduce bladder hypercontractility. This presentation reported on results from a 12-week interim analysis of a 48-week multicenter, randomized, double-blind, placebo-controlled, dose-escalation phase 2a trial assessing the safety and efficacy.

Study enrollment include adult women (40–79 years) with OAB and urgency urinary incontinence (UUI), who were not adequately managed with oral OAB medications, randomized to receive single-dose URO-902 24 mg, URO-902 48 mg or placebo intradetrusor injection. Adverse events (AEs) and postvoid residual (PVR) urine were assessed as well as, change from baseline in mean daily micturitions, urgency episodes, UUI episodes, and quality of life (QoL) measures. This trial was not powered to detect statistically significant differences between groups in efficacy measures. 74 women (mean age 64.7 yrs) were included in the intent-to-treat exposed (ITT-E) population. 13.5% had prior treatment with onabotulinumtoxinA. At week 12, URO-902 24 and 48 mg were associated with clinically relevant improvement vs placebo in mean daily micturitions (LS mean change from baseline, ‒2.5 and ‒3.0 vs ‒1.0, respectively), urgency episodes (‒2.4 and ‒3.4 vs ‒1.2), UUI episodes (‒2.4 and ‒2.6 vs ‒2.3), OAB questionnaire symptom bother score (‒24.1 and ‒25.3 vs ‒11.2), and proportion of patient global impression of change responders (40.9% and 57.7% vs 30.8%). AEs occurred in 45.5% of those receiving URO-902 24 mg, 46.2% receiving 48 mg, and 50.0% receiving placebo.

The most commonly occurring AE was urinary tract infection, one woman (48-mg arm) had asymptomatic elevated PVR urine volume at week 2 which spontaneously resolved without needing catheterization. In summary, a single dose of URO-902 24 or 48 mg was associated with clinically relevant improvement in efficacy and QoL endpoints and was safe and well tolerated. This is promising potential therapy for OAB but further investigation is needed.

Presented by: Kenneth M. Peters, MD, Oakland University William Beaumont School of Medicine,

Written by: Diane Newman, DNP, CRNP, FAAN, BCB-PMD, Urologic Nurse Practitioner, Adjunct Professor of Urology in Surgery, Senior Research Investigator, Perelman School of Medicine, University of Pennsylvania during the International Continence Society Annual Meeting, September 7-10, 2022, Vienna, Austria.

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Phase 2a Trial Results: Promising Gene Therapy for Overactive Bladder - URO-902 Safety and Efficacy Evaluation - Kenneth Peters