The oral beta-3 agonist vibegron, taken once daily at either 50 mg or 100 mg, is well tolerated and results in clinically and statistically significant reductions in daily micturitions, urge incontinence, and urgency episodes.
The oral beta-3 agonist vibegron, taken once daily at either 50 mg or 100 mg, is well tolerated and results in clinically and statistically significant reductions in daily micturitions, urge incontinence, and urgency episodes, according to an 8-week phase IIb study presented at the Society of Urodynamics, Female Pelvic Medicine, & Urogenital Reconstruction (SUFU) winter meeting in Austin, TX.
A drug for overactive bladder in the beta-3 alpha-receptor agonist class hasn’t been approved since mirabegron (Myrbetriq), which has been on the market for several years, according to presenting author Henry David Mitcheson, MD, a urologist in Brighton, MA.
Vibegron, he says, is novel in its selectivity.
“It actually has a very profound selectivity for beta 3 adrenergic receptor-more than 9,000-fold selectivity for beta-3, compared to beta-1 and beta-2. And it has a very favorable clinical and preclinical pharmacokinetic, pharmacodynamics, and toxicological profile,” Dr. Mitcheson told Urology Times.
For the trial, researchers studied 1,395 patients, ages 18 to 75 years, who were randomized to receive once-daily vibegron at a range of doses, including 3 mg, 15, mg, 50 mg, or 100 mg; placebo; tolterodine (Detrol); or a combination of tolterodine and vibegron at either 50 mg or 100 mg. Most of those studied were women, and more than 80% had overactive bladder-wet.
The antimuscarinic antagonist tolterodine was the gold standard drug treatment for overactive bladder. While it continues to be an excellent option, solifenacin (Vesicare) likely is today’s preferred treatment, according to Dr. Mitcheson.
Researchers found vibegron at 50 mg and 100 mg was more effective than tolterodine monotherapy, at 4 mg daily. The combination was as effective at vibegron alone at both doses.
“The take-home message was that, in this dose-ranging study, doses of vibegron at 50 mg and 100 mg were very efficacious in reducing urgency, urge incontinence, and daily micturition numbers. Vibegron was as effective or more so than tolterodine alone,” Dr. Mitcheson said.
All vibegron doses were well tolerated. Incidence of dry mouth was higher with tolterodine, alone, compared to vibegron monotherapy, Dr. Mitcheson said.
But further studies on vibegron are needed, according to Dr. Mitcheson.
U.S. researchers started a phase III vibegron trial in March 2018, focused on a 75-mg dose. Japanese researchers completed a phase III study on the drug, publishing their results in European Urology, and showing vibegron to be efficacious and well tolerated at 50- and 100-mg doses for 12 weeks, according to Dr. Mitcheson (Eur Urol Jan. 20, 2018 [Epub ahead of print]).
“Of course, the beta-3 agonist Myrbetriq is very good. More and more people seem to be using it. This one may be even better-a next generation,” he says. “A concern with Myrbetriq is that it causes hypertension in a small number of patients. This study on vibegron was too short to really pick up any hypertension but none was seen.”
According to the SUFU study abstract, a safety extension to the study suggests that vibegron is well tolerated for up to 1 year of treatment.
Vibegron isn’t the only investigational beta-3 agonist being studied for overactive bladder treatment. Solabegron also is starting phase III research, according to Dr. Mitcheson.
Merck sponsored the trial. Several of Dr. Mitcheson’s co-authors had disclosures related to Merck.
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