Gene Therapy for Overactive Bladder, Incontinence Shows Good Safety, Efficacy

A single dose, at either 24 mg or 48 mg, of URO-902 was safe and well tolerated, while also demonstrating clinically relevant efficacy and improved quality of life in women with overactive bladder (OAB) and urge urinary incontinence (UUI), according to interim results from a phase 2a trial (NCT04211831) presented at the 2022 American Urological Association (AUA) Annual Meeting.¹

At the AUA Annual Meeting, Kenneth M. Peters, MD, professor and chair of urology at Oakland University William Beaumont School of Medicine in Rochester, Michigan, presented on data from the prespecified, 12-week interim analysis of the 48-week trial.

At week 12 of the trial, both 24- and 48-mg doses of URO-902, compared with placebo, demonstrated clinically relevant improvements in the following areas:

• mean daily micturitions (LS mean change from baseline [CFB], ‒2.5 [95% CI, ‒3.5 to ‒1.4; P = .0297] and ‒3.0 [95% CI, ‒4.0 to ‒1.9; P = .0044] vs ‒1.0 [95% CI, ‒2.0 to 0.1], respectively),
• urgency episodes (LS mean CFB, ‒2.4 [95% CI, ‒3.9 to ‒0.8; P = .2060] and ‒3.4 [95% CI, ‒4.9 to ‒1.9; P = 0176] vs ‒1.2),
• UUI episodes (LS mean CFB, ‒2.4 [95% CI, ‒3.4 to ‒1.4; P = .8564] and ‒2.6 [95% CI, ‒3.6 to ‒1.6; P = .5690] vs ‒2.3),
• OAB questionnaire symptom bother score (LS mean CFB, ‒24.1 [95% CI, ‒34.5 to 13.7; P = .0431] and ‒25.3 [95% CI, ‒35.3 to ‒15.2; P = .0246] vs ‒11.2), and
• proportion of patient global impression of change responders (LS mean CFB, 40.9% [95% CI, ‒15.4% to 37.9%; P = .4093] and 57.7% [95% CI, 3.4%-52.8%; P = .0256] vs 30.8%).

Among patients who received URO-902 at the 24- and 48-mg doses, 45.5% (n = 10) and 46.2% (n = 12), respectively, experienced treatment-emergent adverse events (TEAEs), compared with 50.0% (n = 13) receiving placebo. Among all 3 cohorts, the most common AE was urinary tract infection, occurring in 0%, 15.4%, and 3.8% of patients, respectively. One patient on the 48-mg dose arm experienced asymptomatic elevated postvoid residual (PVR) urine volume at week 2, which resolved spontaneously and did not require catheterization.

No TEAEs led to treatment discontinuation, and there were no severe AEs that were related to the agent. Long-term follow-up of the study is ongoing.

“In this pre-specified 12-week analysis of a phase 2a trial of women with OAB and UUI, a single dose of URO-902 24 mg or 48 mg was associated with clinically relevant improvement in efficacy and quality of life and was safe and well tolerated,” Peters concluded.

According to Urovant Sciences, URO-902, an investigational, novel, locally injected gene therapy product (plasmid human cDNA encoding maxi-K channel), has the potential to be the first gene therapy for patients with OAB, and, If approved, could address an unmet need for patients who have failed oral pharmacologic therapies.^2,3

The multicenter, randomized, double-blind, placebo-controlled, dose-escalation phase 2a study included women aged 40 to 79 years with OAB and UUI who were not adequately managed with oral OAB medications. Investigators randomized 80 patients to receive either single-dose URO-902 24 mg (n = 22), URO-902 48 mg (n = 26), or placebo (n = 26) administered by intradetrusor injection via cystoscopy under local anesthesia.

Safety served as the primary end point and was assessed by AEs and PVR urine. Exploratory end points included change from baseline to week 12 in mean daily micturitions, urgency episodes, UUI episodes, and quality of life measures.

Of the 80 patients randomized, 68 completed week 12, and 74 were included in the intent-to-treat population.

Mean age was 64.7 years (SD, 7.1) and 13.5% had prior treatment with onabotulinumtoxinA.

“We are encouraged by these positive results and pending the completion of the study in fall 2022 and we look forward to discussing next steps for the URO-902 clinical development plan,” Sef Kurstjens, MD, PhD, Executive Vice President and Chief Medical Officer of Urovant Sciences, said in a press release.³

REFERENCES

1. Peters K, Enemchukwu E, Kalota S, Greene H. Efficacy and safety of a novel gene therapy (URO-902; pVAX/hSlo) in female patients with overactive bladder and urge urinary incontinence: results from a phase 2a trial. Journal of Urology. 2022;207(5S):e1048. doi:10.1097/JU.0000000000002671.03.

2. Urovant Sciences to present interim data from phase 2a study of potential novel gene therapy, URO-902, and new analyses of data from phase 3 EMPOWUR extension trial of GEMTESA (vibegron) 75 mg at 2022 American Urological Association Annual Meeting. News release. Urovant Sciences April 13, 2022. Accessed May 13, 2022. https://ir.urovant.com/news-releases/news-release-details/urovant-sciences-present-interim-data-phase-2a-study-potential

3. Urovant Sciences announces positive topline results of Phase 2a trial of its potential novel gene therapy, URO-902. News release. Urovant Sciences. March 7, 2022. Accessed May 13, 2022