Evaluating the safety and potential activity of URO-902 (hMaxi-K) gene transfer by intravesical instillation or direct injection into the bladder wall in female participants with idiopathic (non-neurogenic) overactive bladder syndrome and detrusor overact

Two phase 1 trials were performed in healthy women with the overactive bladder (OAB) syndrome and urodynamically demonstrated detrusor overactivity (DO), with the aim to demonstrate the safety and potential efficacy of URO-902, which comprises a gene therapy plasmid vector expressing the human big potassium channel α subunit.

ION-02 (intravesical instillation) and ION-03 (direct injection) were double-blind, placebo-controlled, multicenter studies without overlap in enrollment between studies. Active doses were administered and evaluated sequentially (lowest dose first) for safety. ION-02 participants received either 5000 µg or 10 000 µg URO-902, or placebo. ION-03 participants received either 16 000 or 24 000 µg URO-902, or placebo, injected directly into the bladder wall using cystoscopy. Primary outcome variables were safety parameters occurring subsequent to URO-902 administration; secondary efficacy variables also were evaluated.

Among the safety outcomes, there were no dose-limiting toxicities or significant adverse events (AEs) preventing dose escalation during either trial, and no participants withdrew due to AEs. For efficacy, in ION-02 (N = 21), involuntary detrusor contractions on urodynamics at 24 weeks in patients receiving URO-902 (P < .0508 vs placebo) and mean urgency incontinence episodes in the 5000 µg group (P = .0812 vs placebo) each showed a downward trend. In ION-03 (N = 13), significant reduction versus placebo in urgency episodes (16 000 µg, P = .036; 24 000 µg, P = .046) and number of voids (16 000 µg, -2.16, P = .044; 24 000 µg, -2.73, P = .047) were observed 1 week after injection.

Promising safety and efficacy results in these preliminary phase 1 studies suggest gene transfer may be a promising therapy for OAB/DO, warranting further investigation.

Neurourology and urodynamics. 2020 Jan 16 [Epub ahead of print]

Eric Rovner, Toby C Chai, Sharon Jacobs, George Christ, Karl-Erik Andersson, Mitchell Efros, Victor Nitti, Kelvin Davies, Andrew R McCullough, Arnold Melman

Department of Urology, Medical University of South Carolina, Charleston, South Carolina., Department of Urology, Boston University School of Medicine, Boston, Massachusetts., Ion Channel Innovations, LLC, New York, New York., Department of Orthopaedics, University of Virginia Medical School, Charlottesville, Virginia., Department of Urology, Wake Forest School of Medicine, Winston-Salem, North Carolina., Accumed Research Associates, Garden City, New York., Departments of Urology and Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, California., Department of Urology, Albert Einstein College of Medicine, New York, New York., Department of Urology, Tufts University School of Medicine, Boston, Massachusetts.