Urovant Sciences Ltd., an offshoot of Roivant Sciences Ltd., has kicked off a global phase III trial to evaluate vibegron, an oral beta 3-adrenergic agonist, in adults with symptoms of overactive bladder (OAB). Top-line data from the trial, called Empowur, are expected in 2019. The drug could potentially help millions of people for whom first-line behavioral therapies have fallen short. However, it is likely to face considerable headwinds, too.

In Urovant's favor, American Urological Association treatment guidelines identify drugs in vibegron's class as one of two recommended second-line treatment for OAB. Furthermore, vibegron, licensed to Urovant by Merck & Co. Inc.'s Merck Sharp & Dohme Corp., arrived at Urovant with significant clinical chops. It has been previously evaluated in 16 phase I studies, one large international phase IIb trial in patients with overactive bladder, and a phase III program in Japanese patients with condition.

The Japanese program, sponsored by Merck's Asian-markets licensee Kyorin Pharmaceutical Co. Ltd., yielded news earlier this month with a presentation at the 2018 International European Association of Urology Meeting in Copenhagen. According to Cortellis Clinical Trials Intelligence, more than 1,230 patients with OAB participated in the phase III trial. They were randomized to receive oral vibegron at 50 mg or 100 mg once daily, placebo, or the anticholinergic imidafenacin at 0.2 mg every second day for 12 weeks — the same as the treatment period in Urovant's new study.

Patients receiving vibegron in the phase III study showed significant improvements (p < 0.01) in the number of micturitions per day compared to those treated with placebo. Improvements in daily episodes of urgency, urgency incontinence, incontinence and nocturia, were greater in the group of patients receiving vibegron 100 mg (p < 0.01) over those dosed at 50 mg. The most frequent treatment-emergent adverse events (AEs) were diarrhea, dry mouth, cystitis and nasopharyngitis. There were no serious drug-related AEs reported. Three patients discontinued the study due to treatment-emergent AEs.

Urovant's study, Empowur, will also use a randomized, double-blind, placebo- and active comparator-controlled design and is expected to enroll a similar number of patients to Kyorin's study, about 1,400 men and women with symptoms of overactive bladder.

Participants who meet the eligibility requirements in Urovant's study will be randomized to one of three groups for a 12-week treatment period. Depending on their group, they'll receive either 75 mg of vibegron, a placebo, or a 4-mg dose of extended-release tolterodine, all administered orally once daily. Eligible patients completing the initial 12-week blinded assessment will be offered the opportunity to enroll in a 40-week double-blind extension study to evaluate the safety of longer-term treatment.

The co-primary efficacy endpoints of the study are change from baseline in the average number of micturitions per day in all patients and change from baseline in the average number of urge urinary incontinence (UUI) episodes per day in patients with an average of one or more UUI episodes per day prior to treatment.

Secondary endpoints of the study will include changes in the frequency of incontinence episodes and urinary urgency episodes, and self-reported quality of life scores.

Competition from an Astellas Pharma Inc. drug poised for potential approval at April's end is probably the highest profile threat Urovant may face. The subject of a supplemental new drug application filed in June 2017, Astellas' latest OAB candidate combines two medicines already FDA-approved as monotherapies for the indication: mirabegron and solifenacin, sold as Myrbetriq and Vesicare, respectively. However, that program could face its own challenges, in light of mirabegron's known hypertension risks and the anticipated arrival of generic Vesicare sometime later this year. (See BioWorld Today, Jan. 14, 2015.)

Other potential challengers for all comers in the OAB market are extended-release tolterodine, sold as Detrol LA, and the muscarinic antagonist oxybutynin chloride, sold as Ditropan XL. Allergan plc's Botox (onabotulinumtoxin type A) has also gained favor as a treatment for OAB in certain cases.

Urovant CEO Keith Katkin was unavailable for an interview Wednesday, and the company declined to comment on how it might differentiate vibegron. The company said OAB affects as many as 46 million adults in the U.S., with the most common symptoms including the experience of sudden urges to urinate that cannot be controlled, frequent urination, and urinary incontinence due to involuntary contractions of the detrusor muscle. The underlying cause of OAB remains unclear.