Urovant’s lead investigational product candidate, vibegron, is an oral, once-daily, small molecule beta-3 agonist. The beta-3 adrenergic receptor is the most prevalent beta-adrenergic receptor subtype on the smooth muscle around the bladder. Bladder filling involves the relaxation of this muscle and the contraction of the urethral smooth muscle, while voiding involves contracting the bladder muscle and relaxation of the urethral muscle. Studies of isolated human bladder smooth muscle have shown that selective activation of the beta-3 adrenergic receptor results in smooth muscle relaxation. Therefore, beta-3 stimulation can increase bladder capacity and reduce the symptoms of OAB. Vibegron has been evaluated in multiple clinical trials with a total of over 2,600 OAB patients, including a completed international randomized, double-blind, placebo-controlled Phase 2b study of over 1,300 subjects. Urovant is currently evaluating vibegron in our pivotal Phase 3 clinical trial for the treatment of OAB. In addition to OAB, vibegron is being developed for two additional potential indications: the treatment of OAB in men with benign prostatic hyperplasia (BPH) and the treatment of pain associated with irritable bowel syndrome (IBS).
Overactive Bladder (OAB) is a clinical condition characterized by the sudden urge to urinate that is difficult to control, referred to as urgency, with or without accidental urinary leakage, and usually with increased frequency of urination. Accidental urinary leakage resulting from urgency is referred to a urge urinary incontinence (UUI). More than 30 million Americans over the age of 40 suffer from bothersome symptoms of OAB. Anticholinergic drugs have been the standard of pharmacologic care for OAB. However, anticholinergics are associated with poor tolerability and increasing safety concerns.
BPH is characterized by prostate enlargement, which can block the urethra and prevent normal urine flow, and is progressive with age. There are approximately 40 million men between the ages of 50 and 80 in the United States with BPH, approximately 4.5 million of whom are treated for their BPH symptoms. In addition, approximately 50% of BPH patients also suffer from OAB. A majority of men with BPH and OAB are not treated for their OAB symptoms.
IBS is characterized by recurrent abdominal pain associated with two or more of the following: defecation, a change in frequency of stool and a change in form or appearance of stool. There are approximately 30 million to 40 million Americans with IBS symptoms, 30% of whom consult with their physician. Approximately 80% of these patients identify pain as a symptom contributing to the severity of their IBS. Additionally, IBS presents a significant health care burden and can severely impair a patient’s quality of life. There are no currently marketed drugs indicated specifically for IBS-associated pain.
Urovant’s second investigational product candidate, hMaxi-K, is a novel gene therapy for patients with overactive bladder (OAB) symptoms who have failed oral pharmacologic therapy. hMaxi-K has been evaluated in two Phase 1 studies in OAB patients including a small, double-blind, placebo-controlled Phase 1b clinical trial as an intravesical injection in women with overactive bladder symptoms. Ion Channel Innovations completed the Phase 1b study in 2017 and found hMaxi-K to be generally well tolerated. Efficacy results of the trial, which included a limited number of patients (n=13), indicated dose-dependent improvements in urinary urgency and frequency, achieving statistical significance (p<0.05) in the high dose cohort. Urovant expects to initiate a Phase 2 hMaxi-K study in 2019.