GEMTESA® (vibegron) for the Treatment of Patients with Overactive Bladder FDA Approved - Scott A. MacDiarmid

January 14, 2021

Joining Diane Newman on UroToday's Bladder Health Center of Excellence is Scott MacDiarmid to discuss the United States Federal Drug Administration (FDA) approval of beta-3 agonist, GEMTESA® (vibegron), for the treatment of overactive bladder (OAB). This approval marks the first new oral branded OAB medication approved by the FDA since 2012.


Scott A. MacDiarmid, MD is director of the Alliance Urology Specialists Bladder Control and Pelvic Pain Center Moses H. Cone Memorial Hospital, Greensboro, NC. He completed fellowships in reconstructive urology and urodynamics at Duke University Medical Center in Durham, NC, the University of Otago in Christchurch, New Zealand, and the University of Sheffield in England.

Diane K. Newman, DNP, ANP-BC, FAAN, Adjunct Professor of Urology in Surgery, Perelman School of Medicine, University of Pennsylvania and Co-Director of the Penn Center for Continence and Pelvic Health. She is the author of several books. The most recent is as lead editor of the 1st edition of the SUNA Core Curriculum for Urologic Nursing and of Clinical Application of Urologic Catheters, Devices, and Products.

Read the Full Video Transcript

Diane Newman: Welcome. I'm Diane Newman. I'm an Adult Nurse Practitioner at Penn Urology, University of Pennsylvania, and I specialize in pelvic floor dysfunction. I'm here tonight with a colleague of mine, Dr. Scott MacDiarmid. He's from Alliance Neurology Specialists in Greensboro, North Carolina, and I asked him to share some really new information about a newly approved FDA medication for overactive bladder, vibegron, which brand name will be GEMTESA®. It's a beta-3 edge adrenergic agonist, and it's indicated for the treatment of overactive bladder. Scott, thanks for being here with me to give us some more information on this new beta-3.

Scott MacDiarmid: Well, thanks, Diane. Scott MacDiarmid, Greensboro, North Carolina. I'm a urologist and I sub-specialize in incontinent, I guess you could say leaky bladders. I've been doing it my whole life, and Diane and I are great friends. And I really appreciate Diane asking me to participate in this. We're going to talk about the new beta-3 agonist vibegron GEMTESA®, and it's always nice when there's something new. And in this case, I'm excited because I think we finally have another new treatment tool to help us drive patient-centric excellence in our overactive bladder patients.

I'm just going to go through some nuts and bolts and introduce things here. Vibegron, it's very selective for a beta-3. There are very little beta-1 and beta-2 activity. And it's quite simple. It's once a day, 75 milligrams, with or without food, so it doesn't matter what the patient asks. And the odd patient, they want to cross tablets, e.t.c., capsules, and you can do that with this product. I think this slide really shows us, you know all of the listeners are well aware of how the Musk Renick receptors and beta three receptors pertain to the bladder, its normal and abnormal function, and how that bridges to why antimuscarinics and beta-3 agonists are effective. The beta-3, when you stimulate a beta-3 receptor in the dome of the bladder, the balloon, I say, the bladder relaxes. So it works in the storage phase and not in the voiding phase, which is different than the antimuscarinics. I think the data's important, the company, they know data's important and they really did a beautiful, very large study, over 1500 patients, multi-center, multi-country, placebo control, that looked at the efficacy and safety and tolerability of this new product for the treatment of overactive bladder.

Like pretty well most studies, the average age was about 60, 85% of the patients were women, nearly 80%, about 77% were OAB wet. So there were some OAB dry patients in the study. Unlike a lot of overactive trials there were two primary endpoints being the change from baseline in the mean number of urge incontinence episodes for 24 hours at 12 weeks, and also change in baseline to 12 weeks with a mean reduction in the number of micturitions per 24 hours. There was a whole host of secondary endpoints, but there's actually a key secondary endpoint identified proactively and that was urgency.

And what you see here, the top graph is frequency. The bottom graph is urgency, incontinence. When you look at Figure 1, the decrease in micturitions per 24 hours with drug statistically outperforms the placebo at 2, 4, 8, and 12 weeks with the primary endpoint being at 12 weeks. Figure 2, the bottom half of the slide is the drug GEMTESA® statistically outperform the placebo at 2, 4, 8, and 12 weeks in reducing incontinence episodes with the primary endpoint at 12 weeks. Of note here, at two weeks the product was also statistical. Significant I think the faster a drug works in this space is good for our patients.

Let's go and look at this, this slide here is really right off the package label. It's another way of depicting the information I just showed you. Just go to the upper, the middle of the slide, but the upper half of it, and you'll see the average daily number of urge episodes. And I just want to point out a couple of things here. These patients at baseline were leaking 3.4 times a day when they started taking the medication and placebo and then the mean reduction in terms of percent was approximately 60%. So they were leaking 3.4 times a day. And there was about an average of a 60% reduction in urge incontinence. And again, the drug statistically outperformed placebo. In the bottom half of that slide in the upper aspect of it, you can see the urgency data where the drug actually statistically outperformed placebo in reducing urgency episodes. And that's actually on the label, which is a first for a beta-3 agonist for the FDA to allow it in the label. And it's because prospectively, it was identified as a key secondary endpoint. Volume void is something the FDA likes on package labels, because if you think of all the secondary endpoints, they choose this one over others because what they want is they want to see that the drug is helping you go less frequently because you're holding more. And therefore you void a higher volume and not because someone said, just drink less coffee. And once again here, the drug GEMTESA® statistically outperformed placebo in increasing volume voided.

Just a couple of last slides, we need to talk about tolerability and safety. And we know as clinicians that beta-3 agonists, they're just really well tolerated. And I think when it comes to this product at 75 milligrams, it really is impressive again, in this regard. These are the most common side effects that you see in the Phase III study. And they were headache, nasal pharyngitis, diarrhea, nausea, and upper respiratory tract infection. And you can see the incidence and which was a little bit greater than placebo, but you can kind of see the numbers are getting quite close to placebo, but the definition on the label is you're greater than 2% and you're greater than placebo. And therefore that's what goes on an FDA label adverse reaction table, basically.

I think importantly, and we'll be finishing with this slide is blood pressure. There was no blood pressure effect with this product, and there's no blood pressure discussion, or let's say warning on the label. The blood pressure incidence with GEMTESA® was 1.7%, which is the same as placebo. And they actually did an ambulatory blood pressure study over four weeks versus placebo with 200 patients. And again, the product did not significantly elevate blood pressure. And it's also cardiac safe in terms of there's no QT interval prolongation when you give the medication a much higher than normally prescribed dosages.

In summary, when we think of therapeutic guidelines as first, second, and third-line approaches, the second-line is medications, any muscarinics, and beta-3 agonists, but when you look at all the various treatments, I always sort of say, these are sort of our treatment tools for overactive bladder. And I would say they're so imperfectly good. They work very well in some people and not in others. And we certainly need more treatment tools. And I can honestly say that we have one now after eight or nine years as a new treatment that we have to deliver patient-centric excellence to our OAB patients. And it's going to be an important part of our armamentarium. Thank you very much, Diane. And I'll answer any questions if you have them.

Diane Newman: Scott, that was excellent. And UroToday has an international audience. I want to make sure everybody knows that vibegron was approved by the US FDA for patients with overactive bladder. But I'm excited that we're now going to have another beta-3 medication for our patients. What do you think, where are you going to use this Scott? I mean, I have some ideas about where I'm going to use it. I like this blood pressure data. I think that was really important. Where do you see you using it in your patient population?

Scott MacDiarmid: Well I'm one of those that I'm very pro-beta-3. When I give a medication, you can give a beta-3 first or an anti-muscarinic first. If you asked my two nurses, I mean, if we were counting, I don't know, in the last four years, I might say never have I given any... I always give beta-3 first. I just do. So I'm a big believer because that's what I would take as a patient. That's what I take and I'm trying to drive excellence. You're getting a beta-3 first and here are my samples and I'm allowed to. I'm in private practice and I can deliver samples. And what I see here is another... There isn't data to justify this yet, but like anti-muscarinics, to think that the beta-3, you only need one. I think that's probably not the right answer. That meaning of one beta-3 didn't work now you have a second to try. So to have more of what I prefer to prescribe as a big deal. I think we'll have to prove with data and experience if switch therapy and beta-3 work. I think what's most important for all of us is the more beta-3s we have, it's going to generate more discussion. And physicians, whether they consciously or sort of subconsciously, they sort of make a decision that the beta-3s are going to get used more. Does that make sense to add?

Diane Newman: No, I agree with you. I think that having the second one is going to be important. And I think when you have two medications in the same class, I think that will increase its use. The other, I think really exciting thing about vibegron is the fact that it's one dose. We don't have to worry about flexible dosing with this drug, do we?

Scott MacDiarmid: Yeah. The once a day and makes it nice and easy. I mean, it just does. And I think the blood pressure issue with the competing product was clinically minimal but blood pressure in the eyes of the patient, maybe some physician, that's what they think about. And If you don't have to enter into that discussion or consideration, I think it's a nice thing to have for this medication.

Diane Newman: Well, what else is going on the side effect profile you presented to your right is very insignificant. And I tend to go also to those beta-3s because quite frankly, patients report less side effects with them. Also seeing tertiary patients come into tertiary center, they tend to try something then unsuccessful at the anti-muscarinic. So really I'm excited that we now have this medication approved. Anything else you feel about it? It looks like it does seem to be effective at two weeks, right?

Scott MacDiarmid: Yeah, so I think the rapid onset's good. I would always... I like samples. So if you can get samples, I would still encourage four weeks if you can get them as opposed to two. I mean, if you look at the grass and the data, there's even more benefit at four than there is a two. Now it's nice in the patient's eyes to get that early benefit. But I kind of look at overactive bladder, like golfing. You have good days and bad days, and I'd rather take something for a whole month of any OAB meds. So when they go fill the prescription and get whatever co-pay it's going to be, they can look back over the last month and say, is that worth it? There'll be less false positives and negatives, let's say. I think if you don't give beta-3s first based on whatever reason, I think there are certain populations that, again, clinically, I would say, "Scott, which ones would you do?".

When you thinking about men, when you think about patients with elevated residuals, you're concerned about retention, you're concerned about elderly and anticholinergic side effects or are concerned about CNS issues or dementia concerns that are sort of becoming more concerning, let's say. These are a lot of subgroups that I think medically, as a profession, I can see why we would be given a beta-3 first. I like the drug class so much, I just give it to everybody because I said, that's what I'd like myself.

Diane Newman: Yeah. I agree also. So this medication can be crushed. So it can be used say in an older adult who maybe can't swallow a pill. So I think that's also a positive for some. Really excited. When do you think this will be available? I know it was approved right before Christmas, but when do you think we'll be able to prescribe it. Do they have timeline?

Scott MacDiarmid: Honestly don't know. My knowledge is asking and listening. I haven't heard that. I wish I knew. It's moving so quickly. And I think with the virus, everything is maybe delayed in a sense, but I'm guessing in the next many weeks. 

Diane Newman: That's what I was thinking. If someone said maybe April, it'll be actually out there. So I think it's going to be here sooner than we think probably.

Scott MacDiarmid: I'd like to say to that, and I already mean this, that I think in this case urology, and especially in terms of quality of life things like incontinence that you and I live and die by, Diane, we need the industry to help us. I mean, they bring us the products, they bring out the awareness, they bring out the education and, of course, they benefit. You and I know that, but I think there's a lot of pressure on pharmaceutical companies now to sort of go just at the cancer or niche products. And any company that's there for urology and quality life products, and we have a new one now that's really good. And I'm glad we have a new teammate, let's say.

Diane Newman: Yeah, I agree. We always want something more for our patients because overactive bladder is such a devastating problem. Well, Scott, thanks a lot for giving us this really nice overview and it's really cutting edge information because it's just been approved within the last month. So good luck. Thanks a lot. And I'll see you soon.

Scott MacDiarmid: Just remember us Canadians. Cheers.

Diane Newman: Thanks, everybody. This is a little bit of information on a new medication vibegron, the brand name is GEMTESA®, and given the issue from UroToday. Thanks a lot.