Bladder regulatory peptides hold potential as add-on therapy for overactive bladder symptoms

Low-molecular bioregulatory peptides extracted from bovine bladder tissue may represent a safe and effective add-on therapy for people with benign prostatic hyperplasia (BPH) who experience overactive bladder (OAB) symptoms that are unresponsive to conventional treatments, according to a study presented at the 2025 Annual Meeting of the American Urological Association in Las Vegas, Nevada.

Alpha blockers are considered the mainstay of therapy for BPH, but often have limited efficacy in the treatment of symptoms associated with OAB. As the global burden of BPH continues to increase in the aging population, the search for optimized management strategies continues. Vesusten, a complex of bladder regulatory peptides that have the potential to restore the functional activity of the bladder, has emerged as a potential therapy for OAB. The low-molecular bioregulatory peptides, which are extracted from cattle bladder tissue and undergo ultrafiltration and lyophilization, have been previously studied in the management of neurogenic bladder overactivity in multiple sclerosis (MS). A clinical trial showed that both solifenacin and vesusten were effective therapeutic options for the management of neurogenic bladder overactivity in individuals with MS. However, vesusten showed superiority in the resolution of pollakiuria, urge incontinence, and urgency and demonstrated a sustained therapeutic effect after treatment completion [Abdallah Nemer MN, et al. Urologiia. 2024;(3):63-71].

An open-label prospective randomized phase IV study was designed to assess whether combination therapy with bioregulatory peptides (vesusten) and alpha-blockers is superior to alpha-blocker monotherapy. The study, conducted at Sechenov First Moscow State Medical University in Moscow, Russia, enrolled 100 patients aged between 45 and 80 years who presented with BPH and lower urinary tract symptoms. Follow-up visits were completed by 93 patients (46 from the experimental group and 47 from the monotherapy group). Participants in the experimental group were administered vesusten 5 mg intramuscular injections three times a week, for a total of 10 doses, in addition to daily alpha-blocker therapy, while those in the control group received alpha-blocker monotherapy. All participants received selective alpha-blockers (silodosin or tamsulosin) before enrollment.

Participants underwent uroflowmetry and completed questionnaires assessing improvements in symptoms and quality of life, as well as adverse events, at 60 days. All parameters showed a statistically significant improvement with the addition of vesusten to alpha-blockers. Improvement in International Prostate Symptom Scores was more significant in the vesusten group than in the control group (p<0.001). Bladder-related symptoms as perceived by the patients and their impact on quality of life, reflected in OAB-q and PPBC scores, also improved significantly in patients treated with peptides compared with those who received monotherapy (p<0.001 and p<0.01, respectively). The investigators observed a significant decrease in the rates of urination per 24 hours (measured during 72 hours) as well as less postvoid residual (PVR) urine in the group treated with vesusten compared with the participants who received monotherapy.

A total of 17 mild adverse events, limited to pain and discomfort at the sight of the injection, were reported in the experimental group. None of the participants required additional treatment and the adverse events resolved within a few days.

“When added to alpha blockers in patients with lower urinary tract symptoms due to BPH, vesusten allowed [for significant improvement in] symptoms according to questionnaires, uroflowmetry, and PVR.” the authors concluded. “This therapy did not influence BPH volume. Only mild local adverse events were noted that did not require additional treatment or stopping treatment with the investigational drug.”