Study finds vibegron has no adverse ambulatory effects in patients with OAB

It is important for clinicians to perform ambulatory blood pressure monitoring (ABPM) for patients taking new prescribed medications, as they may affect blood pressure or heart rate in detrimental ways. It is especially important to monitor patients with overactive bladder (OAB), as this group has an increasing abundance of novel medicines available to them.

In a recent study presented at the 2021 American Urological Association Annual Meeting,¹ Michael A. Weber, MD, and co-authors assessed the blood pressure and heart rate profiles of the beta 3 adrenergic receptor agonist vibegron (Gemtesa) in treating patients with OAB. Weber is a professor of medicine and associate dean of research at Downstate College of Medicine, State University of New York, Brooklyn, New York.

Could you discuss the background for this study?

The reason we did this study looking at blood pressure in patients taking vibegron, a new treatment for patients with overactive bladder, is that this new class of drugs in which vibegron is the second in the class, is known as beta 3 agonists. Most doctors know that as soon as you hear the word "beta,” then this is a kind of receptor that is found in the heart and in blood vessels and can affect blood pressure and heart rate and so forth. It's always a concern that when you're using a beta receptor drug—this happens to be a beta 3 receptor agonist, or a stimulator—can you be sure that it's not going to raise the blood pressure, raise the heart rate and do other things that we don't want to see? It shouldn't because beta 3 receptors don't stimulate an increase in heart rate. If anything, they may work the other way. Not that we would normally anticipate that, but that's one of the possibilities. So, that's why we did this study, to make sure. The FDA obviously wanted this done and it's part of the standard approach to make sure that these new drugs are safe.

What were some of the notable findings? Were any of them surprising to you and your co-authors?

The studies were more reassuring and comforting than surprising. I had not anticipated that there would be any adverse blood pressure effects, but of course, you never know, not until you do a study as thorough as this one. And what made this study particularly painstaking is that we didn't just measure blood pressure in patients. We asked patients to wear for 24 hours at a time an ambulatory blood pressure monitor that checked their blood pressure every 15 or 20 minutes by day and by night for the full 24-hour period. And then we started the drug therapy with vibegron or with a placebo. A month later, we repeated the 24-hour monitoring, so we had an enormous opportunity to see if there were any trends, not just an occasional trend in blood pressure, but was something happening in the middle of the day? Something happening in the middle of the night? Something happening when you normally wouldn't see a patient? The answer in the end was no. The data after 4 weeks of treatment were identical, almost literally identical to the data at baseline. So, no change. I think this is very satisfying because it confirmed the integrity of this drug, that it is a beta 3 agonist and it doesn't have beta 1 or beta 2 effects, which sometimes can happen. You think you've made a specific beta 3 drug, but are you 100% sure? Now, we can be pretty close to 100% sure that it is pure beta 3. It works on the bladder, and it relieves the symptoms of people who have overactive bladder, but it doesn't do any adverse things to blood pressure or heart rate.

How reassuring were these findings to you in terms of prescribing vibegron for patients?

I think these findings are going to be quite encouraging. Vibegron as I mentioned before, is the second drug in the class. There's another one, mirabegron [Myrbetriq], with a similar background. And when mirabegron was first developed, there were some concerns. I think people overreacted a little, but in the label from mirabegron, it does suggest to physicians that they check blood pressure carefully in their patients to make sure there isn't some kind of upward change in the blood pressure. This is not part of the label for vibegrom, the newer agent that we work with now. That should give you an extra level of assurance for prescribing it. The anti-cholinergic drugs, which have typically been used for patients with overactive bladder, are reasonably effective. They have some of their own side effects, and I'm not here to talk about that. I'm not a urologist, I don't treat overactive bladder as a routine. But, the great thing about vibegron is that you can prescribe it knowing that there will not be any kind of blood pressure effect that could cause any concern. When you think about it, most patients with overactive bladder are typically in the 60s and 70s. I would say probably half or more of them have hypertension already, so you'd be concerned that if someone's already got high blood pressure, if you do something that can exaggerate or aggravate that situation, you could be doing harm. Well, now we can say, "Don't worry about that. We've got this under control."

What is the take-home message for the practicing urologist?

The take-home message is that this appears to be a very safe drug from a cardiovascular point of view. Of course, we studied over 100 patients with vibegron and 100 with placebo. We looked for all the safety issues, not just cardiovascular, and there was nothing there that was at all surprising or troubling. And so, this does appear to be a drug that could play a very important part in helping to resolve the symptoms of patients who have overactive bladder. It's a difficult condition. It really has an adverse effect on the quality of life of a lot of people. It really limits their activities, sometimes makes it difficult for them at work. Dealing with an overactive bladder is really quite a stressful situation, so here is a new drug that appears to be very safe, that can perhaps add very much to the quality of life for these patients.

Is there anything else you feel our audience should know about the findings?

Right now, I think vibegron is a very safe drug and there are no concerns about any kind of cardiovascular adverse effects.

Reference

1. Weber MA, White WB, King J, et al. Effects of vibegron on ambulatory blood pressure in patients with overactive bladder: results from a double-blind study. Paper presented at: 2021 American Urological Association Annual Meeting; September 10-13, 2021; virtual. Abstract PD66-11