The Effects of Vibegron on Ambulatory Blood Pressure in Patients With Overactive Bladder - Michael A. Weber
September 19, 2021
Diane Newman is joined by Michael Weber discussing a novel medication for the treatment of overactive bladder and a study Dr Weber presented at the AUA 2021 Annual Meeting. Vibegron, a beta-3 receptor agonist is used for the treatment of overactive bladder. Adults with overactive bladder in the age range, 40 to 75, were randomized to treatment either with Vibegron 75 milligrams per day or placebo. At the beginning of the study, ambulatory blood pressure monitoring was done, and after four weeks, repeated, to measure any change from baseline to after four weeks in the blood pressure or the heart rate.
Biographies:
Michael A. Weber, MD, is a Professor of Medicine at Downstate College of Medicine of the State University of New York. He received his medical degree from Sydney University in Australia. His career has focused largely on hypertension and preventive cardiology. He has been a leading part of several of the clinical trials that have helped define strategies for optimizing cardiovascular protection for patients with hypertension. He has also been very much involved with new drug development going back to the beta-blockers and through to the contemporary angiotensin receptor blockers. He is also playing a leading role in current trials of device therapy of hypertension, particularly renal denervation. He was also one of the pioneers in developing ambulatory blood pressure monitoring, a technique now recommended for clinical practice by the major clinical hypertension guideline committees.
Diane K. Newman, DNP FAAN BCB-PMD, Urologic Nurse Practitioner, Adjunct Professor of Urology in Surgery Research Investigator Senior, Perelman School of Medicine, University of Pennsylvania
Biographies:
Michael A. Weber, MD, is a Professor of Medicine at Downstate College of Medicine of the State University of New York. He received his medical degree from Sydney University in Australia. His career has focused largely on hypertension and preventive cardiology. He has been a leading part of several of the clinical trials that have helped define strategies for optimizing cardiovascular protection for patients with hypertension. He has also been very much involved with new drug development going back to the beta-blockers and through to the contemporary angiotensin receptor blockers. He is also playing a leading role in current trials of device therapy of hypertension, particularly renal denervation. He was also one of the pioneers in developing ambulatory blood pressure monitoring, a technique now recommended for clinical practice by the major clinical hypertension guideline committees.
Diane K. Newman, DNP FAAN BCB-PMD, Urologic Nurse Practitioner, Adjunct Professor of Urology in Surgery Research Investigator Senior, Perelman School of Medicine, University of Pennsylvania
Related Content:
GEMTESA® (vibegron) for the Treatment of Patients with Overactive Bladder FDA Approved - Scott A. MacDiarmid
Vibegron Statistically Significantly Improves Quality-of-Life Measures in Patients with Overactive Bladder: EMPOWUR Study
Urovant Sciences Presents Positive Ambulatory Blood Pressure Data Showing That GEMTESA® (vibegron) 75 mg in Overactive Bladder Was Not Associated with Statistically Significant or Clinically Meaningful Effects on Blood Pressure or Heart Rate
GEMTESA® (vibegron) for the Treatment of Patients with Overactive Bladder FDA Approved - Scott A. MacDiarmid
Vibegron Statistically Significantly Improves Quality-of-Life Measures in Patients with Overactive Bladder: EMPOWUR Study
Urovant Sciences Presents Positive Ambulatory Blood Pressure Data Showing That GEMTESA® (vibegron) 75 mg in Overactive Bladder Was Not Associated with Statistically Significant or Clinically Meaningful Effects on Blood Pressure or Heart Rate
Read the Full Video Transcript
Diane K. Newman: Welcome. I'm Diane Newman. I'm a nurse practitioner at the University of Pennsylvania in the Division of Urology, and I'm here today as one of the editors at UroToday.com, interviewing an expert in the area of hypertension. I want to introduce to you, Dr. Michael Weber, he is a Professor of Medicine at Downstate College of Medicine of the State University of New York. His career has focused largely on hypertension and preventive cardiology. He was the editor-in-chief of The Journal of Clinical Hypertension until 2019, and this is the official journal of The World Hypertension League.
He has been a lead investigator for several of the clinical trials that have helped define strategies for optimizing cardiovascular protection for patients with hypertension. He has also been very involved with new drug development, going back to the beta-blockers. And today I'm going to have him present some research that he has been involved in with the new beta-3 adrenergic agonist, Gemtesa. Dr. Weber is going to present the research that he recently presented at the AUA. Welcome, Dr. Weber.
Michael A. Weber: Well, thank you very much, Diane. And it's a real pleasure to have this opportunity to talk to colleagues about this new medication for the treatment of overactive bladder and looking in particular at an important safety issue. We have studied Vibegron, one of the new beta-3 receptor agonists that are now in use for the treatment of overactive bladder, with a particular focus on making sure that this new agent did not have an adverse effect on blood pressure. And you may ask, why would we be concerned about something like that? Well, let's look at the background. We know that there are different kinds of drugs being used for patients with overactive bladder disease, including anticholinergics, and more recently the beta-3 adrenergic receptor agonists. And we worry about that a little bit because drugs that start with the beta, particularly the beta-blockers, are known to work on beta receptors in the heart and in the vasculature in general.
And this of course is not a beta-blocker. This is a beta-agonist, so a bit of concern. Could it be that this drug may have the unwanted effect of raising blood pressure or raising heart rate? Well, the best way to study it, and this is what in fact, the FDA insists on, is to do ambulatory blood pressure monitoring, where we measure the blood pressure for a full 24 hour period. And I'll show you in a moment what that looks like and see whether there is any evidence that perhaps wouldn't be obvious in a usual office visit, to indicate some sort of blood pressure change with these drugs.
This is very simply what we did. We took adults with overactive bladder in the age range, 40 to 75, the average was just about 60, typical isn't it, three quarters of them were women. Again, what you would expect. And they were randomized to treatment either with Vibegron 75 milligrams per day or placebo. And at the beginning of the study, we did ambulatory blood pressure monitoring, and after four weeks, we repeated the ambulatory blood pressure monitoring and asked the question, "Was there a change from baseline to after four weeks in the blood pressure or the heart rate?" We screened 455 people with overactive bladder, and that was necessary for us to actually be able to randomize 108 to placebo and 106 to Vibegron.
These are the patients, I'm not going to spend time on this. Just very simply again, the average age was 60, three-quarters of them were women and the blood pressure was well controlled. Now some of them actually had hypertension, but we allowed them to stay on their blood pressure medications. So the blood pressures in general were pretty low when we started the study. And this is what we found. And a lot of people find it quite fascinating to see what blood pressure looks like over 24 hours. Let's just look for instance at the placebo. And we are starting here at 8 o'clock in the morning, this is 10:00 PM. And now overnight and back to the next morning. And you can see during the day the blood pressure is fairly high. And then as we start to get towards evening, it starts falling and it falls and it falls and it falls and is at its lowest pressure during sleep. And then it starts to rise again in the early morning hours.
This is very characteristic of blood pressure and we worry about it. Is there going to be some sort of effect on blood pressure in the early morning hours as the blood pressure was shooting up? Because some people actually have an overshoot which can be dangerous. But putting all that aside, what we see here is that at baseline in placebo, this solid line shows what their blood pressure was and you can barely see it, but this open circle line, this theta line, is what happened after four weeks. Absolutely identical, totally superimposable. If you averaged out all the blood pressures throughout the day, because we measured blood pressure every 15 or 20 minutes in these patients, they're wearing a portable device that inflates every 15 minutes and measures their blood pressure.
So we have dozens and dozens of readings. If you average it out, there was zero difference between baseline and four weeks. And the same over here in the Vibegron group, we're looking at the systolic pressure, no change, not even 1 millimeter of mercury difference, whether you looked just at the daytime or the whole 24 hour period. And the same is true for the diastolic pressure, here placebo, and here Vibegron. So absolutely no evidence for a change in blood pressure and absolutely no evidence for a change in heart rate.
So these data just summarizing what I just showed you, no need to go through these numbers again, safety for things other than blood pressure, just exactly what you'd expect. These patients do occasionally get complaints of one sort or another, probably not related to the drugs, three or four people in both groups got hypertension, but that's typical because some people's blood pressure, in fact, all of our blood pressures fluctuate from time to time. So you'd expect a few people to increase their pressure and become hypertensive. This is offset by a few people, reducing their blood pressure and no longer being in the hypertensive branch. So again, no evidence for any safety concerns. And so, to summarize what we found was there was no evidence of any meaningful or even nonmeaningful, there was just no change in blood pressure or heart rate with Vibegron in this study. And overall Vibegron was safe and well-tolerated. So thank you for allowing me to share this data with you.
Diane K. Newman: Now, this is really, really interesting. Now, why do you think this is because there is another agent out there and it does affect blood pressure. And we do know the beta-3s can. Why do you think this agent, because it looks like really, really startling data that there really was no effect at all?
Michael A. Weber: Well, I think the problem is Diane, that when we call a drug, a beta-agonist, as with most kinds of drugs, there are different degrees of agonism and different degrees of specificity. We're calling this a beta-3 agonist. So theoretically, it doesn't work directly on the beta receptors on the heart or the artery. So it should be pretty clean, but it's possible that there could be just a little bit of beta-1 or a little bit of beta-2 among all the beta-3. And maybe one brand versus another brand, we may see a little bit more of that beta-1 effect, which could raise the pulse rate a little and could raise the blood pressure a little. I do not think even with the other beta-3 agonists, hypertension is a major problem. I think, for the most part, it's a well-tolerated and effective drug as well. But I think Vibegron really does have a pretty clear picture, as far as blood pressure is concerned, it just doesn't seem to change it.
Diane K. Newman: What about the heart rate? Now I saw the one slide that you did monitor the heart rate also. Was there...
Michael A. Weber: Yeah, it was exactly the same [inaudible 00:09:21] it didn't change by even one beat a minute. It was remarkably constant. Now these were people of around 60 years of age and usually, people who volunteer for clinical trials, are pretty responsible people, they are the sort of people who are willing to give up their time and go through the whole process of a clinical trial because they know they are helping other people by providing data. They're going to guide future treatment for a wide range of patients. So they are usually pretty reliable and responsible people. Who knows what could happen with the people mistaking their medications, taking excessive doses of medications. But I thought this was pretty reassuring.
Diane K. Newman: Now, you said you had some who did also have a diagnosis of hypertension. I'm assuming that these were people that have controlled hypertension on medications. You just allowed them to come into the study, right?
Michael A. Weber: That's right. We allowed them to come in, even if their pressure was a little bit higher than what you might call perfect control, which these days, of course, we've made it harder to get proper control of hypertension because the new rule is you got to be less than 130 over 80. It used to be 140 over 90. So it's a bit of a struggle now for some people. But we let people in up to 140 over 90, that was not a problem. And maybe they were taking two or three drugs for that. And we were fine because that's the real world, isn't it? A lot of people, I'm sure in your practice, you see a lot of people with hypertension probably more often than not.
Diane K. Newman: No, you're right. It's almost like every other person has hypertension. You're right. And many have uncontrolled hypertension. So you're right. The new definition I think has thrown us a little bit. So this data, helped them with their label, didn't it, as far as with the FDA, as far as having this blood pressure data?
Michael A. Weber: Yes. Yes. Because there is no specific warning about hypertension or blood pressure effect. So it did help with the label. I believe there are other drugs where hypertension or the possibility of changes in blood pressure is mentioned and doctors ask to be careful and to scrutinize blood pressure carefully. Now, I assume that anytime anyone comes to your clinic or most responsible clinics, the pressure is going to be checked in any case. It's kind of a global thing as people come through the door, but it's nice to know that the FDA was satisfied that there is not a blood pressure issue with Vibegron.
Diane K. Newman: Well, listen, Dr. Weber, thank you very much for doing this for us. I know this audience that comes to UroToday will be very interested in this and it's really great to get this cutting end research on a new medication for overactive bladder. Thank you.
Michael A. Weber: Well, thank you, Diane. My pleasure.
Diane K. Newman: Welcome. I'm Diane Newman. I'm a nurse practitioner at the University of Pennsylvania in the Division of Urology, and I'm here today as one of the editors at UroToday.com, interviewing an expert in the area of hypertension. I want to introduce to you, Dr. Michael Weber, he is a Professor of Medicine at Downstate College of Medicine of the State University of New York. His career has focused largely on hypertension and preventive cardiology. He was the editor-in-chief of The Journal of Clinical Hypertension until 2019, and this is the official journal of The World Hypertension League.
He has been a lead investigator for several of the clinical trials that have helped define strategies for optimizing cardiovascular protection for patients with hypertension. He has also been very involved with new drug development, going back to the beta-blockers. And today I'm going to have him present some research that he has been involved in with the new beta-3 adrenergic agonist, Gemtesa. Dr. Weber is going to present the research that he recently presented at the AUA. Welcome, Dr. Weber.
Michael A. Weber: Well, thank you very much, Diane. And it's a real pleasure to have this opportunity to talk to colleagues about this new medication for the treatment of overactive bladder and looking in particular at an important safety issue. We have studied Vibegron, one of the new beta-3 receptor agonists that are now in use for the treatment of overactive bladder, with a particular focus on making sure that this new agent did not have an adverse effect on blood pressure. And you may ask, why would we be concerned about something like that? Well, let's look at the background. We know that there are different kinds of drugs being used for patients with overactive bladder disease, including anticholinergics, and more recently the beta-3 adrenergic receptor agonists. And we worry about that a little bit because drugs that start with the beta, particularly the beta-blockers, are known to work on beta receptors in the heart and in the vasculature in general.
And this of course is not a beta-blocker. This is a beta-agonist, so a bit of concern. Could it be that this drug may have the unwanted effect of raising blood pressure or raising heart rate? Well, the best way to study it, and this is what in fact, the FDA insists on, is to do ambulatory blood pressure monitoring, where we measure the blood pressure for a full 24 hour period. And I'll show you in a moment what that looks like and see whether there is any evidence that perhaps wouldn't be obvious in a usual office visit, to indicate some sort of blood pressure change with these drugs.
This is very simply what we did. We took adults with overactive bladder in the age range, 40 to 75, the average was just about 60, typical isn't it, three quarters of them were women. Again, what you would expect. And they were randomized to treatment either with Vibegron 75 milligrams per day or placebo. And at the beginning of the study, we did ambulatory blood pressure monitoring, and after four weeks, we repeated the ambulatory blood pressure monitoring and asked the question, "Was there a change from baseline to after four weeks in the blood pressure or the heart rate?" We screened 455 people with overactive bladder, and that was necessary for us to actually be able to randomize 108 to placebo and 106 to Vibegron.
These are the patients, I'm not going to spend time on this. Just very simply again, the average age was 60, three-quarters of them were women and the blood pressure was well controlled. Now some of them actually had hypertension, but we allowed them to stay on their blood pressure medications. So the blood pressures in general were pretty low when we started the study. And this is what we found. And a lot of people find it quite fascinating to see what blood pressure looks like over 24 hours. Let's just look for instance at the placebo. And we are starting here at 8 o'clock in the morning, this is 10:00 PM. And now overnight and back to the next morning. And you can see during the day the blood pressure is fairly high. And then as we start to get towards evening, it starts falling and it falls and it falls and it falls and is at its lowest pressure during sleep. And then it starts to rise again in the early morning hours.
This is very characteristic of blood pressure and we worry about it. Is there going to be some sort of effect on blood pressure in the early morning hours as the blood pressure was shooting up? Because some people actually have an overshoot which can be dangerous. But putting all that aside, what we see here is that at baseline in placebo, this solid line shows what their blood pressure was and you can barely see it, but this open circle line, this theta line, is what happened after four weeks. Absolutely identical, totally superimposable. If you averaged out all the blood pressures throughout the day, because we measured blood pressure every 15 or 20 minutes in these patients, they're wearing a portable device that inflates every 15 minutes and measures their blood pressure.
So we have dozens and dozens of readings. If you average it out, there was zero difference between baseline and four weeks. And the same over here in the Vibegron group, we're looking at the systolic pressure, no change, not even 1 millimeter of mercury difference, whether you looked just at the daytime or the whole 24 hour period. And the same is true for the diastolic pressure, here placebo, and here Vibegron. So absolutely no evidence for a change in blood pressure and absolutely no evidence for a change in heart rate.
So these data just summarizing what I just showed you, no need to go through these numbers again, safety for things other than blood pressure, just exactly what you'd expect. These patients do occasionally get complaints of one sort or another, probably not related to the drugs, three or four people in both groups got hypertension, but that's typical because some people's blood pressure, in fact, all of our blood pressures fluctuate from time to time. So you'd expect a few people to increase their pressure and become hypertensive. This is offset by a few people, reducing their blood pressure and no longer being in the hypertensive branch. So again, no evidence for any safety concerns. And so, to summarize what we found was there was no evidence of any meaningful or even nonmeaningful, there was just no change in blood pressure or heart rate with Vibegron in this study. And overall Vibegron was safe and well-tolerated. So thank you for allowing me to share this data with you.
Diane K. Newman: Now, this is really, really interesting. Now, why do you think this is because there is another agent out there and it does affect blood pressure. And we do know the beta-3s can. Why do you think this agent, because it looks like really, really startling data that there really was no effect at all?
Michael A. Weber: Well, I think the problem is Diane, that when we call a drug, a beta-agonist, as with most kinds of drugs, there are different degrees of agonism and different degrees of specificity. We're calling this a beta-3 agonist. So theoretically, it doesn't work directly on the beta receptors on the heart or the artery. So it should be pretty clean, but it's possible that there could be just a little bit of beta-1 or a little bit of beta-2 among all the beta-3. And maybe one brand versus another brand, we may see a little bit more of that beta-1 effect, which could raise the pulse rate a little and could raise the blood pressure a little. I do not think even with the other beta-3 agonists, hypertension is a major problem. I think, for the most part, it's a well-tolerated and effective drug as well. But I think Vibegron really does have a pretty clear picture, as far as blood pressure is concerned, it just doesn't seem to change it.
Diane K. Newman: What about the heart rate? Now I saw the one slide that you did monitor the heart rate also. Was there...
Michael A. Weber: Yeah, it was exactly the same [inaudible 00:09:21] it didn't change by even one beat a minute. It was remarkably constant. Now these were people of around 60 years of age and usually, people who volunteer for clinical trials, are pretty responsible people, they are the sort of people who are willing to give up their time and go through the whole process of a clinical trial because they know they are helping other people by providing data. They're going to guide future treatment for a wide range of patients. So they are usually pretty reliable and responsible people. Who knows what could happen with the people mistaking their medications, taking excessive doses of medications. But I thought this was pretty reassuring.
Diane K. Newman: Now, you said you had some who did also have a diagnosis of hypertension. I'm assuming that these were people that have controlled hypertension on medications. You just allowed them to come into the study, right?
Michael A. Weber: That's right. We allowed them to come in, even if their pressure was a little bit higher than what you might call perfect control, which these days, of course, we've made it harder to get proper control of hypertension because the new rule is you got to be less than 130 over 80. It used to be 140 over 90. So it's a bit of a struggle now for some people. But we let people in up to 140 over 90, that was not a problem. And maybe they were taking two or three drugs for that. And we were fine because that's the real world, isn't it? A lot of people, I'm sure in your practice, you see a lot of people with hypertension probably more often than not.
Diane K. Newman: No, you're right. It's almost like every other person has hypertension. You're right. And many have uncontrolled hypertension. So you're right. The new definition I think has thrown us a little bit. So this data, helped them with their label, didn't it, as far as with the FDA, as far as having this blood pressure data?
Michael A. Weber: Yes. Yes. Because there is no specific warning about hypertension or blood pressure effect. So it did help with the label. I believe there are other drugs where hypertension or the possibility of changes in blood pressure is mentioned and doctors ask to be careful and to scrutinize blood pressure carefully. Now, I assume that anytime anyone comes to your clinic or most responsible clinics, the pressure is going to be checked in any case. It's kind of a global thing as people come through the door, but it's nice to know that the FDA was satisfied that there is not a blood pressure issue with Vibegron.
Diane K. Newman: Well, listen, Dr. Weber, thank you very much for doing this for us. I know this audience that comes to UroToday will be very interested in this and it's really great to get this cutting end research on a new medication for overactive bladder. Thank you.
Michael A. Weber: Well, thank you, Diane. My pleasure.