Urovant’s Vibegron Flops In IBS Study
Decision on OAB Indication Awaits
Executive Summary
Another disappointment for irritable bowel syndrome therapies as Urovant Science’s vibegron fails in a Phase II trial, likely spelling the end for the investigational indication.
Urovant Sciences, Inc.’s oral beta-3 agonist vibegron has missed its primary endpoint in a Phase IIa study in the treatment of irritable bowel syndrome (IBS) pain.
The news comes as Urovant awaits the verdict of the US Food and Drug Administration on its new drug application for the product in the treatment of overactive bladder (OAB). The Prescription Drug User Fee Act goal date is 26 December.
The Phase IIa trial of 75mg vibegron once daily in 222 women with abdominal pain due to IBS with IBS-D (diarrhea) and IBS-M (mixed IBS) missed the primary endpoint, with 40.9% of vibegron IBS-D patients achieving at least a 30% improvement in average worst abdominal pain over the week 12 period, compared with 42.9% in the placebo group. A responder was defined as a subject with at least a 30% decrease in “worst abdominal pain in the past 24 hours” compared with the weekly baseline average over the 12-week period.
The study also missed the most important secondary endpoint of proportion of Global Improvement Scale (GIS) responders at week 12. In the vibegron group, there were 42.4% GIS responders at week 12 for IBS-D patients, compared with 33.3% for placebo, which was not statistically significant.
Vibegron was at least very well tolerated in the study, and analysts at Biomedtracker said that since the issues concerning this Phase II trial were efficacy-related as opposed to safety/tolerability-related, “Urovant will focus its resources into developing vibegron for the treatment of OAB.”
In addition to the NDA for OAB, the drug is advancing in its Phase III program in men with overactive bladder and benign prostatic hyperplasia (BPH).
Urovant’s only other product is URO-902, which is in a Phase IIa program for OAB. URO-902 is a naked plasmid DNA gene therapy expressing the Maxi-K or SLO alpha large-conductance calcium and voltage-activated potassium ion channel. It causes smooth muscle cells to produce more potassium channels and thus relaxes them.
Urovant was launched by Roivant Sciences in 2017 with a license to Merck & Co., Inc.’s then-Phase III vibegron OAB candidate as its first project, and last December, Urovant submitted the NDA seeking approval of once-daily vibegron for OAB patients with symptoms of urge urinary incontinence, urgency and urinary frequency.
The hope is that it will compete with Astellas Pharma, Inc.’s beta-3 agonist Myrbetriq (mirabegron). The only other beta-3 agonist in clinical development for OAB is
Velicept Therapeutics, Inc.’s solabegron, which is in Phase II, and also in Phase II for IBS.
Currently, Urovant is about 72% owned by Sumitovant Biopharma Ltd. In December 2019, Sumitomo Dainippon Pharma Co., Ltd.. paid $3bn in cash to exercise a previously announced option to acquire five Roivant Sciences biopharmaceutical divisions, one of which was Urovant. SDP is operating these through a newly formed, wholly owned subsidiary called Sumitovant.
Earlier this month, Sumitovant announced that it would acquire the remaining 18% of Urovant that it does not already own, in a transaction expected to close in the first quarter of next year.
It will pay $16.25 per share (a 106% premium) in cash for each outstanding share of Urovant common stock not already owned; this equates to an equity value of approximately $584m on a fully diluted basis, or an enterprise value of $681m, after accounting for Urovant’s $210m in debt and cash of approximately $112m. (Also see "Deal Watch: Lilly Finds New Partners For Genetic Disorders, Protein Degradation" - Scrip, 25 Nov, 2020.)