Gopal H. Badlani, MD, discusses the recently presented long-term safety profile of the β-3 adrenoceptor agonist vibegron.
Gopal H. Badlani, MD
It has been quite a while since a new drug was introduced to address quality-of-life issues in patients with overactive bladder (OAB). David Staskin, MD, has been the champion of many of the prior agents launched in the market and leads the presentation of the long-term safety profile of the β-3 adrenoceptor agonist vibegron detailed in a recent article.
There have been a number of articles published on this drug, starting with Masaki Yoshida, MD, et al introducing the “novel” agent,1 to the long-term efficacy data in Japanese patients,2 to the post hoc analysis of the phase 2 data to evaluate its effect on nocturia.3 The EMPOWUR (NCT03492281) study mentioned in this month’s issue was published with 12 weeks of trial data.4
There are several key questions. One, is this drug effective? The clear answer is yes. When compared with placebo in a large data set, it was marginally better than its comparator in efficacy, adverse effect of dry mouth, and discontinuation rate. The most remarkable data in this long-term report show its continued use in over 85% in this funded and monitored study, as it is much lower in real-world use.
The next question is, does this bring something new to the table compared with the other β-3 adrenoreceptor agonist mirabegron (Myrbetriq)? Vibegron has no interaction with CYP enzymes compared with mirabegron. When compared with tolterodine, the drug was slightly better in efficacy and dry mouth rate. The effect on heart rate, although a caution in the labeling for this class of agents, has not been a frequent clinical issue.
Will this change the paradigm of treatment? This is unlikely, as currently in the US, at least 2 antimuscarinics have to be tried before a β-3 agonist can be prescribed. The cost of the drug, when available, may make a difference, as right now there is only a single drug in this class of agents.
In this study, as well as with all other drugs for OAB previously studied, the placebo arm has a remarkable influence on voiding behavior, emphasizing the role of bladder diaries and behavioral influence of attention to the voiding parameters. Thus, apps to record voiding and/or prompt patients may be the biggest advance we make in this field.
Badlani, a Urology Times® editorial consultant, is professor and vice chair of urology at Wake Forest Baptist Medical Center, Winston-Salem, North Carolina.
1. Yoshida M, Takeda M, Gotoh M, et al. Vibegron, a novel potent and selective β 3-adrenoreceptor agonist, for the treatment of patients with overactive bladder: a randomized, double-blind, placebo-controlled phase 3 study. Eur Urol. 2018;73(5):783-790. doi:10.1016/j.eururo.2017.12.022
2. Yoshida M, Kakizaki H, Takahashi S, et al. Long-term safety and efficacy of the novel β 3 -adrenoreceptor agonist vibegron in Japanese patients with overactive bladder: A phase III prospective study. Int J Urol. 2018;25(7):668-675. doi:10.1111/iju.13596
3. Yoshida M, Takeda M, Gotoh M, et al. Efficacy of novel β 3 -adrenoreceptor agonist vibegron on nocturia in patients with overactive bladder: A post-hoc analysis of a randomized, double-blind, placebo-controlled phase 3 study. Int J Urol. 2019;26(3):369-375. doi:10.1111/iju.13877
4. Staskin D, Frankel J, Varano S, et al. International phase III, randomized, double-blind, placebo and active controlled study to evaluate the safety and efficacy of vibegron in patients with symptoms of overactive bladder: EMPOWUR. J Urol. 2020;204(2):316-324. doi:10.1097/JU.0000000000000807