Investigational drugs for bladder pain syndrome (BPS) / interstitial cystitis (IC)

ABSTRACT

Introduction: Bladder pain syndrome (BPS)/interstitial cystitis (IC) is associated with sensory lower urinary tract symptoms. Unfortunately, many of the existing oral treatments are ineffective in most patients of BPS/IC, which is the motivation for developing new drugs and therapeutic approaches. This review covers the latest drugs that have been investigated in BPS/IC patients. Intravesical treatments offer the opportunity to directly target the painful bladder with less systemic side effects.

Areas Covered: In this review, the authors analyze the existing literature supporting the treatment of BPS/IC with conventional drugs including heparin, hyaluronic acid, chondroitin sulfate, and dimethylsulfoxide (DMSO). Furthermore, investigational drugs such as tanezumab and adalimumab, capable of sequestering nerve growth factor (NGF), and Tumor necrosis factor-α (TNF- α) are discussed. Investigational treatments such as liposomes, botulinum toxin (BTX), liposomal BTX, PD-0299685 (a Ca²⁺ channel ɑ2δ ligand), continuous intravesical lidocaine, and AQX-1125 (a novel SHIP1 activating compound) are also covered.

Expert opinion: New investigational drugs offer promising improvements in clinical outcomes for BPS/IC patients; however, BPS/IC is a chronic pain disorder that is very vulnerable to a strong placebo effect. In addition, BPS/IC is a heterogeneous disorder that can be classified into several phenotypes. Since different phenotypes of BPS/IC respond differently to systemic and intravesical treatments, the authors believe that new drugs developed for BPS/IC are more likely to meet their predetermined clinical endpoints if the inclusion/exclusion criterion is tailored to specific phenotype of BPS/IC patients.

KEYWORDS:

• Bladder pain syndrome
• botulinum toxin
• liposome
• interstitial cystitis
• intravesical therapy

Article highlights.

• Latest guidelines on bladder pain syndrome (BPS)/interstitial cystitis (IC) recommend to reduce delay in diagnosis and treatment.

• Pathophysiology of BPS/IC is multifactorial involving epithelial permeability and/or neurogenic inflammation, activation of mast cells.

• The signaling pathways underlying these pathophysiological mechanisms are promising therapeutic targets.

• Hyperexcitability of afferent neurotransmission is attenuated by botulinum toxin and newer drug PD-0299685.

• Early clinical data indicate potential of liposomes in improving BPS/IC symptoms alone and together with botulinum toxin.

• To date, several drugs targeting neurogenic inflammation and mast cells have been tested on patients.

This box summarizes key points contained in the article.

Declaration of interest

The authors are supported by an Interstitial Cystitis Association pilot grant. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.