Stay updated on recently FDA-approved medications crucial for pharmacists.
Gain essential insights on new drugs approved in the last 12 to 18 months, ensuring accurate dispensing and effective patient education.
The GameChanger
SweatControl Patch approved for primary axillary hyperhidrosis.
Update in treatment for Alzheimer's with mild cognitive impairment.
Host
Joe Strain, PharmD
Clinical Faculty, Monument Health
South Dakota State College of Pharmacy
Pharmacist Members, REDEEM YOUR CPE HERE!
Not a member? Get a Pharmacist Membership & earn CE for GameChangers Podcast episodes! (30 mins/episode)
CPE Information
Learning Objectives
Upon successful completion of this knowledge-based activity, participants should be able to:
1. Discuss the therapeutic indications of recent FDA-approved medications.
2. Describe unique pharmacological properties for each new medication.
0.05 CEU/0.5 Hr
UAN: 0107-0000-24-098-H01-P
Initial release date: 03/11/2024
Expiration date: 03/11/2025
Additional CPE details can be found here.
Stay updated on recently FDA-approved medications crucial for pharmacists.
Gain essential insights on new drugs approved in the last 12 to 18 months, ensuring accurate dispensing and effective patient education.
The GameChanger
SweatControl Patch approved for primary axillary hyperhidrosis.
Update in treatment for Alzheimer's with mild cognitive impairment.
Host
Joe Strain, PharmD
Clinical Faculty, Monument Health
South Dakota State College of Pharmacy
Pharmacist Members, REDEEM YOUR CPE HERE!
Not a member? Get a Pharmacist Membership & earn CE for GameChangers Podcast episodes! (30 mins/episode)
CPE Information
Learning Objectives
Upon successful completion of this knowledge-based activity, participants should be able to:
1. Discuss the therapeutic indications of recent FDA-approved medications.
2. Describe unique pharmacological properties for each new medication.
0.05 CEU/0.5 Hr
UAN: 0107-0000-24-098-H01-P
Initial release date: 03/11/2024
Expiration date: 03/11/2025
Additional CPE details can be found here.
Hey, ce plan members From CE Impact. This is Game Changers. I'm Jen Moulton and this week I'm excited to welcome a guest to our podcast who I've known and worked with for a really long time, Joe Strain, who is at the South Dakota State University College of Pharmacy and practices at Monument Health. Welcome, joe.
Speaker 2:Thanks, Jen, for having me.
Speaker 1:Yeah, yeah, I'm excited. I'm excited to have you on the show because I think we've worked together. How many years have you done the new drug program for us at the Pharmacy Expo? I?
Speaker 2:believe this was year nine, if my math is correct.
Speaker 1:Nine. Okay, I was originally thinking it was like six or seven, so even longer. How did we get started working together?
Speaker 2:Well, I think originally it started that I've been doing new drug updates at the South Dakota Pharmacy Association meeting for about 20 years. When I first started as a junior faculty member, very first year out of the gate they invited me. I think it was a new faculty member that needed some of the new drugs. Then it just became an annual thing after that. Here we are 20 years later. It was nine years ago. I believe you guys had always had a new drug update at your convention. I think the gentleman that normally did it was not available that year. I did a fill in and then I continued on from there.
Speaker 1:We went from there. Yeah, low man on the totem pole who?
Speaker 2:knows, right yeah.
Speaker 1:Into something that you do every year. I love it. Well good, you do it for not just us, but for other people as well.
Speaker 2:I do Sometimes one of the other health associations, like I've done it for PAs, nurse practitioners, and just really kind of hit the highlights for them, we'll once in a while speak at one of their conventions as well.
Speaker 1:Yeah, yeah, that's great. Yeah, we used to have Dan Hussar did it for us for a lot of years. It's been great to work with you for nine years. I love this topic. It's always a crowd favorite at the conference every year. I think it's because it's just a nice. You kind of wrap it up in a bow. Here's all the new drugs in the last year. Here's the important things you need to know about. Obviously, we see the new drugs and we hear about them, but they take a little bit to get to market. By the time that happens, the newness of that has worn off. It's just a good reminder of what are the important aspects of this. What do the costs look like? How's it going to fit into therapy? I love it. I always learn a ton. I appreciate you doing a little recap for us today.
Speaker 2:Yeah, absolutely. I enjoyed as well. Even though you're rarely going to use all the new drugs that come to market, depending on your clinical practice, I think it's still viable to kind of have an idea what's out there, because you never know a friend's family. With the direct to consumer marketing that companies are doing, you may get a question at any time if it's something you're not even familiar with. It can be a little awkward, At least if you've heard of it. Sometimes it gets you a start and you kind of know where to end with that conversation.
Speaker 1:Yeah Well, and especially with direct to consumer advertising, there's nothing worse than somebody saying what is that You're like? I don't know. It's the first I've heard of it.
Speaker 2:Yeah, I think we've all been there in that regard, because I don't watch a lot of shows and a lot of TV. That puts you in that awkward position.
Speaker 1:Yeah, yeah, so true, good. Well, I am going to let you kind of run with it today and I can jump in if I've got some questions, but otherwise I'm going to let you run with it, so take it away.
Speaker 2:Yeah.
Speaker 2:So, as Jen mentioned, when we did this in a more kind of a detailed setting at the Pharmacy Expo in Iowa here last month, this is going to be a little more of an abbreviated version of that today. We'll kind of take a 10,000 foot overview of these new medications and we'll certainly mention the name and what they're marketed under. For a brand name, we'll also talk about the therapeutic indications that were approved by the FDA. We'll also mention what class it falls into whether it's kind of a new class or whether it falls into an existing class of medications, and the setting of where it's something new. We'll try to maybe mention a little bit more about the pharmacology. We'll also pull out kind of one of the key clinical trials. Usually the FDA has reviewed at least a couple of clinical trials. We'll try to pull out kind of one key phase three trial that kind of is representative of the efficacy data behind each medication and then we'll talk about the dosage and dosage forms that we'll be utilizing and then the cost. I think we have cost availability for all but one of the medications we'll talk about today and then at the end I'll kind of wrap up with kind of the top three things to know about each medication, kind of. In my opinion. Now, it's certainly not a comprehensive list and I would guess refer you to a more detailed handout which is available for CE plan members as a reference, and so there is more information that'll be contained in that handout if you're interested in particular about a certain medication that we're going to discuss today. So with that I think we'll get started and dive right into it.
Speaker 2:The first drug we're going to talk about is doprutostat, marketed under the name just doobrox. Some of these are kind of a mouthful to say, and it was always kind of a. I think I spent half my time trying to figure out how to pronounce some of these medications to kind of get started. But this one's going to be approved for patients with chronic kidney disease, to treat anemia, and these chronic kidney disease patients need to be have been on dialysis for at least four months. Okay, so if you think about, you know, treating anemia and chronic kidney disease patients, we typically would use one of the EPO agents. That's been commonly done for for a long time.
Speaker 2:But now we have an oral version of this, basically an oral alternative to try to increase the Rithropoietin levels. Now, pharmacologically it's unique to anything else on the market, at least in the United States, and it's how what it fits into as far as a class it's considered a reversible inhibitor of the hypoxia inducible factor, prolohydroxylase. Now that's kind of a mouthful but essentially what it's doing is kind of inducing a, making the body think it's in a hypoxic state, and so it increases transcription factors by inhibiting that HIF, prolohydroxylase, and that will lead to the increased transcription of a Rithropoietin. So kind of an alternative method to try to increase Rithropoietin levels without just giving EPO. Now, from an efficacy standpoint, if we look at the Ascend D trial so this is looking at a dialysis population in comparing to Prutostat directly with Rithropoietin, and these were patients that had been on Rithropoietin already and then they went through a four week washout phase and then were enrolled either to Prutostat or Rithropoietin and what the trial was intending to look at was the change in hemoglobin from baseline to weeks 28 to 52. So they're basically looking at the average hemoglobin over that 28 to 52 week timeframe and essentially what they showed with this medication is that it maintained or increased hemoglobin levels very similar to Rithropoietin, so deemed to be non inferior to Rithropoietin. The other outcome they looked at was major adverse cardiovascular events. That's something that's always been a potential concern with the EPO agents, in particular, if you raise the hemoglobin maybe too fast or too to too great of degree, and that's always a concern. And so that's one of the major safety outcomes that the FDA wanted to evaluate, and what they showed in this trial was that the adverse cardiovascular events were not any higher compared to Rithropoietin. So at least based on this trial data, it appears to be as safe from a cardiovascular standpoint.
Speaker 2:Now, if we look at how to dose this medication, it's going to be based on pre treatment hemoglobin levels if they have not been on one of the EPO agents previously, and I'm going to refer our listeners here to one of the tables either in the packaging or in the handout. Those are all spelled out rather than kind of going through this in great detail. But just know that you're going to base your starting dose on the pre treatment hemoglobin level if they haven't been on it before. But if they've been on one of the EPO agents, there's also a table available for a dose conversion. So, depending on what dose they're already on, that will dictate what dose you would start these patients on. For to produce that.
Speaker 2:Now it comes as a number of different dosage forms one, two, four, six and eight milligrams. You can actually go up to 12, 16 and 24 milligrams as well by combining tablets. So there's different dosing tiers, as you will. If you go through this and again this is all spelled out in some tables in the labeling so you'll figure out your starting dose based on one of the initial dosing tables and then we can dose adjust every four weeks by basically stepping up by one strength or by down by one strength, and we may have to go up or down depending on. You know the response we're getting for the hemoglobin. If we increase too quickly, which should be defined by one gram per deciliter over two weeks, or by more than two grams per deciliter or four weeks then we actually dose decrease them and then at any point if the hemoglobin increases above 12 grams per deciliter, then we would actually stop treatment altogether. Thank you.
Speaker 2:Now, if we look at cost of this medication, it's kind of a tiered cost based on the strength of the tablet you're going to use. The one milligram is $140 for 30 tablets, going on up to the eight milligram tablet at over $1,000 for that, and this is the AWP pricing. Now Most patients aren't going to be paying that directly because 87% of our dialysis patients are on Medicare and this is part of the Medicare bundled payment, based on the research that I did in talking with one of our pharmacists that works in the dialysis unit. Now we have not switched over at our unit yet to this. But as far as the cash price, it certainly is cheaper than the erythroplating agents. But again, as far as that dialysis and the bundled payment goes, if you work with this population, that's certainly something you'd maybe want to investigate and figure out how that payment's all going to shake out when switching to this. But at least from the face value with the cash price payment, it does appear to be a potential option.
Speaker 2:So if we kind of wrap this up and talk about kind of the top three things that you kind of want to remember about Duprita stat, just keep in mind it's basically a daily oral option for patients that are on dialysis to try to treat their anemia. Think of this as an alternative to using erythroplating. Now the question is will patients be compliant? Right Now when they come into the dialysis unit, you can assure compliance because you know they're going to be. You're going to be giving it to them when they're at dialysis, but this is going to be something they're going to be required to do on a daily basis. It's simple, it's a once daily oral tablet, so it's not overly complicated, but it does require them to take it at home and we do still have to check iron stores. So keep that in mind, just like we do with patients that are on erythroplating, we have to check iron stores and make sure we adequately replenish those iron stores for this drug to be effective. And then just keep in mind it does appear, based on the current data we have, that it works at least as well as the other as erythroplating, and it does have similar cardiovascular risk as that agent.
Speaker 2:Next medication we're going to go into is Solbactam-Durlobactam, and this we market under the brand name Zac Durl, and this actually has a very specific indication. So it's a new antibiotic specifically indicated for hospital acquired pneumonia or ventilator associated pneumonia caused by susceptible strains of Acinetobacterobamini. And this is relevant because the CDC has put carbapenem, resistant Acinetobacterobamini on the most urgent threat list, and so when we talk about resistant microbes and you know microbes that we're really concerned about on a national level this is on that most urgent threat list, and a lot of that stems from we just didn't have a lot of great treatments for it, and so it's nice to have another agent approved for this for this bacteria. Now, pharmacologically, you're probably familiar with Solbactam. It's combined with Ampicillin for the product unicin, and so we've used that for years and we think of Solbactam as really a beta-lactamase inhibitor, which it is. But it also has actually specific antimicrobial properties against a limited number of microbes, with one of those being Acinetobacter. It'll bind to the specific penicillin binding proteins that that bacteria does express, and so it does have activity against that. Now it's combined with Durlobactam, which is a next generation beta-lactamase inhibitor, and this is important because Durlobactam is a very kind of a broad spectrum beta-lactamase inhibitor. It'll inhibit Class A, class C as well as Class D beta-lactamase enzymes, and that's important because Acinetobacter will express some of those broad spectrum enzymes and that will provide resistance against our antimicrobials. And so by combining these two agents, we have a very kind of a targeted drug that's meant to be used for Acinetobacter infections.
Speaker 2:Now, from an efficacy standpoint, it's interesting that this is the attack three phase, three trial data that I'm going to discuss here. They only had about 60 patients in each treatment arm and they looked at Sylbactam Durlobactam. Compared to Cholistan, 60 patients isn't a whole lot, but when you're talking about infectious disease trials with a very specific bacteria, sometimes there's just very limited numbers that you're going to be able to recruit for those trials. Now I'll give the trial authors credit here is they were in that they were just looking at the carbapenem resistant strains of Acinetobacter for their primary outcome and that was looking at all-cause mortality at day 28. And what they showed here for the Sylbactam Durlobactam group was the mortality rate was 19 percent versus 32 percent for the Cholistan group. So about a 13 percentage point difference, which was statistically determined to be non-inferior. So what we can really say is that it works as well as Cholistan. But when you look at it on a numeric basis, you know 19 percent mortality versus 32 percent mortality. I know certainly which arm I'd rather be in based on those numbers, right.
Speaker 2:And so if you look at dosing of this medication, it's going to be it's a think of it as a Betalactam antibiotic. It's going to be renally. It's going to have some renal dose adjustments, but the standard dose is going to be one gram every six hours and can be used for seven to 14 days, based on the trial data. And then we are actually going to go up or down the dose based on the renal function, and so again, I'd refer you to the labeling to kind of get those renal dose adjustments. It's also going to be infused over three hours. That's going to take advantage of our time over MIC properties with our Betalactam agents. So we were certainly doing that with some of our other agents, common to do that with things like Zosin as well.
Speaker 2:And now availability and cost. When we look at that aspect of this medication, it comes actually as three vials. As far as the kit that it's going to come in, you have to mix up all three vials together before you're going to give it and then, once you do that, you got to give it within 24 hours. Now the AWP cost on this medication is around $190 per dose. So if you're going to be doing four doses a day, which is kind of the average or the dose for average or good kidney function, I guess, if you will, and that's going to be around $760 per day, so for an AWP cost which is a fair amount, but again, you're going to be using this for, you know, at most a week to two weeks, and certainly some of our other newer agents, they kind of fall into that same ballpark for a price.
Speaker 2:So if you're going to think about the top three things about this medication, keep in mind it's really meant to be used for carbapenem resistant acinetobacter bominine infections. Most of these patients did have pneumonia in the clinical trials, so it's specifically approved for pneumonia due to that bacteria. And keep in mind they had improved numeric outcomes from a mortality standpoint compared to Clistin. But the other nice thing is that it had far less acute kidney injury compared to Clistin. Clistin had about a 36% incidence of acute kidney injury in that trial, versus only 6% with the sulbactam duralabactam. So about a 30 percentage point difference. And so certainly you know, works at least as well, if not you know, numerically a little bit better, and it appears to be much safer from a renal toxicity standpoint. So certainly a welcome agent to the market Right?
Speaker 2:Next struggle to talk about is Fiesel Linnitant or Vioza is the brand name that will be marketed under, and this is has the potential to hit a very large population because it's indicated for moderate to severe vasomotor menopausal symptoms and it's estimated up to, you know, a million people are impacted by this on an annual basis, so a very large market to potentially target. Typically, we'll use a lot of our estrogen products to help treat some of these symptoms. But we know some patients aren't really a candidate for estrogen products. Maybe they have a contraindication to it, or maybe they just don't prefer an estrogen product and so they're looking for an alternative way to treats and can try to control some of these symptoms. And so this agent prevents.
Speaker 2:It presents a unique option. It is a non hormonal treatment and pharmacologically it is unique compared to anything else in the market. It is what's called a neurokinin three receptor antagonist. Now what does that mean? Well, normally what neurokinin does is would bind to this kiss peptin neurokinin dinorphin neuron, and that is abbreviated the candy neuron, kndy, and it's actually called the candy neuron. And by binding to that neuron it helps, it moderates activity in the hypothalamus and leads to these menopausal symptoms. Now normally what happens is estrogen would inhibit that process, and but when our estrogen levels decline, when the patient set menopause, then this system ramps up and then induces those menopausal symptoms. So basically, what we have here is an alternative way to block that process by having a neurokinin three receptor antagonist.
Speaker 2:Now, from an efficacy standpoint, I'm just going to discuss data from the Skylight 1 trial, which is a phase 3 trial. There were actually a couple trials out there that evaluated this medication and what they looked at was Fiesel Inotent compared to placebo. They had around 175 patients in each arm and they were looking at patients that on average had around 10 moderate to severe vasomotor symptoms per day, and so these patients were fairly significantly impacted by these symptoms and they started them on the treatment. Then they looked at the change in the number of daily symptoms at week 4 and then at week 12. So the primary efficacy standpoint was really a 12-week trial, and what they found was a significant decrease in these daily symptoms compared to placebo. I'm about to reduce to about two symptoms per day compared to placebo at week 4 and around 2 and 1 half to 3 at week 12. So that was deemed to be significant.
Speaker 2:Now the one thing where the jury may be still a little out on this is that what impact does it have on sleep? We know sleep is a big problem with menopause symptoms as well. They looked at a number of secondary and then some exploratory endpoints with this medication as far as its impact on sleep and with the one secondary endpoint where they're asking patients to kind of use a scale to rate their sleep, it actually did not show a significant finding at week 12 in this trial. Now the other trial that I have not seen fully published yet reportedly did show a significant impact on sleep. So it's kind of a mixed bag there. And then in the exploratory outcomes with this trial they looked at kind of another rating scale where they look at the global impression of change and sleep disturbance and basically what they were showing was the severity of sleep symptoms tended to decrease a little bit with the treatment group. So again it's an exploratory outcome, so probably requires further investigation to kind of fully define its role in improving sleep symptoms.
Speaker 2:Now from a dosing standpoint it's fairly straightforward. It's a 45 milligram tablet once a day, so it's fairly simple to take. The wholesale acquisition cost price is around $550 per month, so it's fairly expensive. But there is a patient assistance program out there and so if patients are eligible they can get this for as reportedly as little as $30 per month. And keep in mind, in that trial they were looking at a four-week outcome period and patients did show a significant improvement. So at least if they could try it for a month, they might get an idea of how well it works for them, and that would be certainly beneficial from a cost standpoint.
Speaker 2:So if we're going to think about the top three things with this medication, certainly keep in mind it's a novel mechanism. It's a non-hormone-based therapy shown to reduce the number of daily moderate to severe menopausal symptoms, mostly like hot flashes, is what we're looking at improving. One thing that did come up in some of the long-term safety trials is that there was a little bit of an increase in LFTs and about a 1.5 percentage point increase over placebo, and so it is recommended to monitor at baseline the ASTALT in Billy Rubin and then follow it every three months after that. So that is one thing to keep in mind that patients should be monitored for. And then if you're looking at the latest kind of guidelines on menopause, at least from the North American Menopause Society, this drug actually is recommended as a first line option to help reduce those hot flashes. But just keep in mind I think really the impact on sleep probably requires a little bit further research before we can make some definitive statements on its impact there.
Speaker 2:All right, the next drug we'll talk about is Rizofungin, or Rizayo is the brand name this is going to be marketed under and this is a new antifungal agent specifically approved for patients with Candidemia or invasive Candidiasis. This is really approved under a limited use approval by the FDA. So basically, if patients don't have another great option, then this becomes something to consider. Now, pharmacologic, it kind of sounds like an akinokandin, with the last name Fungin, and that's because it is. It's very similar to Caspifungin, mycophungin and Nidgula Fungin, and so from a mechanism standpoint it's very similar. It works on the fungal cell wall to help inhibit that enzyme there that is critical to cell wall, fungal cell wall synthesis.
Speaker 2:Now, from an efficacy standpoint, looking at the Restore Phase 3 clinical trial that was done, they had a little over 90 patients in each arm and they compared it to Caspifungin, which is nice because it works similar to that, and they looked at a couple different primary outcomes, one to appease the FDA and one for the European Medicines Agency may have different requirements as far as what they want companies to look at in regards to efficacy, but bottom line summary is basically it showed that it worked just as well as Caspifungin and in the FDA required outcome was looking at mortality at 30 days, and it was very similar to that, at least from a statistical standpoint. Now, from a dosing standpoint, this is going to be a 400 milligram dose initially and then 200 milligrams once a week after that, and there's no data really beyond four weeks with this medication. It is going to be expensive, though. The AWP is over $2,000 per vial and if you're looking at a four week course, you're looking at an AWP of close to just under $12,000 for that whole course. So it is an expensive agent. So top three things about this medication. The thing that really makes it unique and would make it a potential option for some patients is that it's a once weekly kind of canon. Most of these are kind of canons you are given on a daily basis, but this has a long half-life of 150 hours, and so that's where this has a niche. I would say it would serve as an option for those outpatients that are unable to de-escalate maybe to an oral azole agent or unable to come into an infusion center to get a once daily kind of canon. Then this would be a potential option for those patients. Now, one safety finding that showed up with this with Riza Fungin, that didn't show up with the other kind of canons is that it does cause some photosensitivity, and so we'd have to warn for some sun exposure with this particular product if a patient is going to be on it.
Speaker 2:The next drug we'll talk about here is Lacanumab, or Lacanby is the brand name of this product, and this is a medication that was approved for Alzheimer's with mild cognitive impairment or mild dementia, and this is really the second monoclonal antibody that's going to work on reducing amyloid beta plaques that has come to the market. Aducanumab has come to the market, and actually the company has just recently announced that they are going to kind of remove it from the market and no longer pursue that one. They're going to focus their energy on this latest one, lacanumab, and so I guess the question is you know, is this one going to be a lot better? That one was brought with a few things along the way. There were some safety issues, efficacy was kind of called into question and also cost. When they initially launched it, the cost was pretty astronomical. So we'll take a look at this drug, discuss this in a little more detail to see if there's see what differences there might be here.
Speaker 2:So just want to start off and looking at the efficacy data behind this one and this is going to discuss data from the Clarity Alzheimer's trial. This is a phase three trial. Looking at it compared to placebo, again, they had a fairly large number of patients 859 in the Canyon Mab Group, 875 in the placebo group. They looked at similar outcomes as they did in the Attica-Numab trials. Looking at the baseline clinical dimension rating scale, some of the boxes score okay and that's can be a little bit difficult to, I think, interpret unless you're familiar with that. But what they did is they took a baseline assessment of that score and then followed patients for 18 months and then reassessment, found out how much their score increased. The higher the score, the worse they're doing from a cognitive standpoint. And what they showed over that 18 month period is that there was a 0.45 difference in that score between the Lacanumab Group and the placebo group. And so I think the question with that is what does a 0.45 point difference really mean? And if you're able to access these slides, I have a clinical application slide involved in there and you can kind of look at the specific tables to help sort that out. I'll kind of walk you through it now. But basically at baseline patients would fall into a very mild dementia category in both groups and then in the placebo group they progressed into the mild dementia category, whereas in the Lacanumab Group they kind of progressed somewhere in between the very mild dementia and mild dementia. So it was just a slight difference there. Now there's been previous articles, at least one article published that would suggest that you need at least a one point increase to show a really clinically significant difference with this scoring system between treatment groups. And keep in mind with the difference was 0.45, so it didn't reach a full point with this. So I bring that up mainly just to kind of bring up that.
Speaker 2:There's the clinical applicator. The clinical significance of the difference between this and placebo has been called into question by some of the people in this field. So if we look at the dosing of this medication, it's a 10 mgs per kilo every two weeks. So patients are gonna have to come in usually to like an infusion center to get a one hour infusion to this medication every couple of weeks. The average cost of this medication is gonna be around $26,500 per year, so it's fairly expensive and Medicare is reportedly gonna cover this because it does have a full approval. So that is a potential option. So, and again, the impact on Medicare costs would be potentially huge If a large number of patients that theoretically a large number would be eligible for this. So if all of them are gonna be using it, it would have a big impact on that spending too. So top three things I think to know about, like CandyMab, is that the benefit, that the clinical meaningful benefit, has been called into question.
Speaker 2:The other thing I didn't talk about in great detail has to do with some of the safety outcomes, in that we still have to monitor for these ARIA findings. This is this amylide related imaging associated with edema or hemositterin findings, and essentially what that is is finding either edema on the brain or a little bit of bleeding on the surface of the brain as well, this accumulation of hemositterin which can lead to some neurotoxic findings. Now, most patients weren't symptomatic that had these, but they did find it to a fairly high percentage, just on surveillance by doing MRIs. And so we'd still have to do an MRI at baseline and then follow up MRIs prior to the fifth, seventh and 14th infusion. And so there's gonna be some involved imaging with this. And then patients also have to be eligible for this medication by having a PET scan to confirm that they have these amylide plaques at baseline. So there's some it's an involved process in order to get patients on this medication.
Speaker 2:The other thing that we don't know is what do we do with patients that are on anticoagulation. There wasn't a lot of patients that were on full dose anticoagulation the trial. They didn't really tease that out because they didn't have a large, robust number. But there have been a couple of case reports. One was a patient getting an alteplase for acute stroke and they had a ended up dying. That patient had died and they had a intracranial hemorrhage. And then another patient on a PIXA band had an intracranial hemorrhage as well. Now, those are just case reports. Those things can happen anyway. So I can't say there's this is necessarily causing those things, but it's certainly something that would probably require further monitoring and investigation and there is ongoing trials with this drug. They're gonna enroll these patients into some longer term four or five year trials and so I think more data to come on the really the clinical impact from an efficacy standpoint and the safety outcomes as well. So these are definitely things to kind of keep on the radar. All right.
Speaker 2:Next we'll talk about is the VGPant or Zavspret is the brand name of this one and this is gonna be approved for the treatment of acute migraines and adults and pharmacologically it's similar to a few other agents we have on the market and that it's a calzotone and gene-related peptide receptor antagonist, and so that can help with some of the vasodilation and pain signaling that's involved with migraines. So it's very similar to Ramee, japan, ibrojapan and Atojapan as far as how it works. Now this drug was compared to placebo in the efficacy trials and what they looked at was the percentage of patients that were pain free two hours after administering the drug for an acute migraine. They also looked at the percentage of patients that had their most bothersome symptom go away at two hours, and what they showed was about a nine percentage point difference between the Zavijapan group and the placebo group, which, you know, while there's no direct comparison of this agent to any of the other similar agents on the market, if you look at those other trials, the difference between those drugs and the placebo is somewhat similar to what this one is showing to, but again, we don't have any direct comparison data From a dosing standpoint.
Speaker 2:What makes this one a little bit unique is that it comes as a nasal spray and so it's administered as a 10 milligram single spray and one nostril as needed for acute migraine. Only use one dose a day and it's recommended to only use a max of eight doses per month. That's the max that was studied. It does come as just a single spray device, so use it and then toss it, and there's six doses per carton. Cost is a little more than the other agents in this class that are used for acute treatment. This one, the AWP, is around $220 per dose, whereas the other ones are reported kind of in the 120 to 150 range. So it is a little bit more expensive.
Speaker 2:But if we look at the top three things about this medication, know that it's for acute migraine treatment. The primary outcome is looking at relief at two hours. However, there was a percentage of patients that did see relief as early as 15 to 30 minutes. So for some patients they do get a fairly acute relief and that's certainly welcome for migraines. It's very well tolerated. Really, the major side effect was taste disorders, which were pretty minor and tended to go away pretty quickly. So that wasn't a big detriment to use. And then just keep in mind it's a nasal formulation and certainly for some patients, they get severe nausea and vomiting with their migraines, and this may be a welcome delivery to try to avoid any oral medication if you typically suffer from a lot of nausea and vomiting.
Speaker 2:All right, the next drug we'll talk about is Zeranolone, or Zerzouvet is the brand name of this one, and this is our first oral treatment for adults with postpartum depression, and so this is certainly got a specific niche to the market. Pharmacologic, it's going to mimic allopregnanolone. We believe it's a drop in those levels that contribute to the postpartum depression. It's actually very similar to the drug Brexanolone, which was approved for this indication back in 2019. However, the problem with that medication was that it required a 60-hour IV infusion and that brought in all kinds of logistical issues of trying to get patients admitted to a facility, and the cost was certainly high with this one as well. So basically, what it's doing is helps to restore GABA, a receptor function that tends to get affected by that drop in the allopregnanolone.
Speaker 2:Now, if we look at one of the efficacy trials looking at the Skylark trial, this was comparing Zeranolone to placebo in about 100 patients in each arm, and what they looked at was the Hamilton depression rating scale. So the Hamdys 17 scoring system, which is a common rating scale, used to assess the severity of depression and on average baseline patients had around a 29 scored at 29 points, which would fall into the severe depression category. And then they looked at the change in that Hamdys score over 15 days so very short period here as far as the depression goes and what they showed was a four-point difference with Zeranolone versus placebo, which was statistically significant. So basically, patients went from the severe depression category down to the mild depression category in the Zeranolone group and that was, you know, certainly improved over placebo. And if you look at how quickly it worked, they actually started seeing separation from placebo as early as day three, and so that's certainly welcomed when you're talking about depression, when we typically oftentimes are waiting weeks for that to have an impact. Again, the primary outcome was at 15 days and it did kind of take a full 15 days to get to that kind of max effect. They did continue to follow patients out to day 45, and those effects were sustained.
Speaker 2:So this is a it's an interesting drug in that you just take 50 milligrams once a day in the evening and it's only taken for 14 days, so it's a very short course. It's not meant to be used long term, at least not at this time. They actually did look at trying to get it approved for major depressive disorder and was denied approval for that indication. But so for this specific indication it's just used for 14 days. It needs to be taken with food high fat meal. So that's another little kind of caveat to remind patients of. It also does cause some sedation and so we can reduce the dose if it causes too much sedation. We do have to remind patients to take it at night and then don't drive for 12 hours. So hopefully, if they take it at night, maybe 7, 8 pm, as long as they're not having to drive anywhere until 7, 8 am, give it that 12 hour break before driving. That will help.
Speaker 2:It does come as a 20, 25, and 30 milligram capsule. There's some various dose adjustments for hepatic and renal impairment, that, and then also some dose reductions for somnolence, that and so between those three dosage forms that can all be figured out. It is expensive though. A 14 day course keep in mind just a 14 day course of this is AWP is $19,000. So it's definitely priced that. They've. I kind of got a niche in the market here. Now there is a patient assistance program, so it's obviously we're going to be probably encouraging patients to. We're going to investigate that and see if they're eligible to get them some assistance there. At this time it's just going to be distributed by specialty pharmacies and it is a schedule for medication.
Speaker 2:Brexanolone was as well. There was some mild dependence associated with this and so there can be some very mild side effects as they come off this medication, but again, most were mild to moderate, didn't appear to have a huge impact. So top three things about Xaranolone keep in mind it's the first oral agent for postpartum depression. We have not had a lot of you know, great therapies for this. It works fairly quickly, which is welcomed. As early as three days Patients may start seeing some benefit. Again, it's just taken for 14 days though, but keep in mind it does have a high rate of somnolence, so warning patients not to dry for 12 hours after taking this is going to be important. The somnolence rates were around 36% and fair number of patients did undergo a dose reduction to try to minimize some of that somnolence as well. All right.
Speaker 2:Next drug we'll talk about is Geparone, marketed in the brand name Exua, and this is approved for major depressive disorder in adults. Now, pharmacologically it works as a selective agonist at the serotonin 1A receptor and if that sounds familiar to another drug on the market it's because it's an analog of Buisperone. So it works very similar to Buispar. Now Buispar is not approved for major depressive disorder, it's more of a generalized anxiety disorder medication that can be utilized. But this works fairly similar to that but has a different indication for major depressive disorder. Now, from an efficacy standpoint, one of the trials that kind of helped get the drug approved they had compared it to placebo, about 100 patients in each treatment arm. Again, looking at the baseline, the HamD 17 scores, that Hamilton depression rating score Now these patients had more of a moderate depression at baseline, around between 22 and 23 points at baseline, and then over an eight week treatment period they showed about a two and a half point difference between the treatment group with Gepron and placebo. So again trying to get them down closer to kind of that mild depression category.
Speaker 2:Now, from a dosing standpoint, this is going to be a little bit involved in that. You have to titrate them up, start them low, titrate them up. There's kind of some odd dosing with this. It's 18.2 milligrams is the dose you start out. It's once daily and then on day four you can go to 36.3, day seven 54.5. And then after day 14, 72.6. So again, kind of some odd doses, and if you're running to side effects you can slow that down a little bit as well or back off the dose if needed.
Speaker 2:This is one drug that has not hit the market as of yet. It was. It's targeted to be out in early 2024. Obviously, right now, as we record this today, it's early 2024. So I thought it might be out yet, but this is something that you'll have to stay tuned to as far as trying to figure out the cost, because that is not available as of yet.
Speaker 2:So top three things about Gepron. I know that it's a technically going to be marketed as a new serotonergic antidepressant, but keep in mind it's similar to Buse-Bron as far as how it works. The one potential advantage, you know, from a antidepressant standpoint, is it doesn't cause any weight gain or sexual dysfunction like some of the agents do. I mean, we do have others that don't do that as well, but this is where it may get a little bit of attention and some patients may want to try it from that standpoint. But it does have a high rate of dizziness at about 49% in one of the clinical trials and 35% incidence of nausea in one of the trials. And so those were the most common side effects and that's part of the reason why we start them low and titrate them up slowly and then kind of see how things are going before we get too aggressive with the dosing. Again, most of that was mild to moderate, didn't lead to a lot of treatment discontinuation though. All right.
Speaker 2:Just want to briefly mention just a couple other medications that hit the market. One of those is sodagliflowsen, marketed under the brand name in PEPA. This is going to really target cardiovascular patients. It's an SGT2 inhibitors, you know, similar to the other SGT2s in the market, but it also inhibits SGT1. And that helps to block sodium and glucose absorption within the GI tract. There was some concern that that may increase GI side effects, about a maybe two to three percentage point increase in one of the trials over the placebo group, as far as the incidence of diarrhea. So didn't appear to be at least huge in that trial.
Speaker 2:But this one's going to be used specifically approved I should say to reduce the risk of cardiovascular death, hospitalization for heart failure and urgent heart failure visits, so you're going to think of this kind of that heart failure and diabetes population. As far as targeting its use, it is fairly expensive. I think the list price was around $600 a month for this one, so it kind of falls in line with some of the other SGT2s. The other agent that was approved that's similar is as Bexigal flows in, or Brinzavi, and this is SGT2 inhibitor, and it's just approved for type two diabetes. That's the only place it was studied. The unique thing about this one is it's going to be available through cost plus drugs, and the cash price on this one is listed at just under $50. And so it's significantly cheaper from a cash price standpoint than the other SGT2 inhibitors now, so that may be attractive. A patient doesn't have insurance. Keep in mind, though. There is no cardiovascular outcomes data with this medication as of yet, so those trials have not been done.
Speaker 2:Another agent that came to market last year was Vonoprazin, or Vokesna. Now this is an agent that was actually approved in 2022. It's a combination with Amoxicillin as a dual pack, or Amoxicillin and chlorothromycin as a triple pack for H Pallori, but now it's available as a monotherapy agent, specifically a roasted gastroesophageal reflex disease and relief of associated heartburn. This is a medication that's actually been approved in Japan since 2015, so I have quite a bit of experience with it in that country. So if you consider a potassium competitive acid blocker works somewhat similar to our proton pump inhibitors, but it does block active and resting proton pumps and does not require acid for activation.
Speaker 2:There's some evidence out there. Maybe it's a little bit more of a potent inhibitor than the PPIs, but we do know that the PPIs work for a lot of people and you know and do provide that relief. So if you look at it in the overall population for this kind of erosive suffagitis gastritis, they showed it to be similar to lanzoprazole, so similar to previsit in the outcomes that they were looking at. However, when they looked at the more severe disease grade C and grade D a suffagitis, they did show us a superior outcome, with one of the secondary outcomes with Vonoprazin compared to lanzoprazole. So I don't think this is going to be necessarily a first line agent up front because the cost is $20 per day. However, if you have a more severe case or a patient that maybe is not getting the response or looking for the PPIs, then this would certainly come into play and might in, should in, could be considered All right.
Speaker 2:The last drug that I'm going to kind of mention or really it's maybe more of a device, if you will I always kind of pull out something a little bit unique to the market, and this is what is known as the Brella sweat control patch, and so this is specifically approved for primary axillary hyper hydros, hyper hyper hydrosis, so excessive armpit sweating, essentially is what you want to consider this for. So if there would be a patch that's actually you go into a provider's office, they would apply the patch for three minutes. That's not all that long, life for three minutes. And what if the patch has in it is sodium. It's essentially a sodium patch. It interacts with water that generates a targeted amount of heat energy and then that heat energy causes a micro thermal injury to the sweat glands, leading to an activation of those sweat glands. So it's going to inactivate the sweat glands and then it's going to work for into reduce sweating for about a two month period. So and it was shown to be better than that could the sham that they were using to compare it against, and they show that a higher percentage of patients had more than a 50% reduction in the amount of sweat they produced compared to the sham.
Speaker 2:So if there's any part of your job that you think isn't glamorous, so just keep in mind that someone out there is measuring the amount of axillary sweat produced in these clinical trials, and so I can't imagine that's all that fun either.
Speaker 2:So, but anyway, so it's kind of a unique product. There's certainly other ways to combat this condition. It's it's something that actually does impact a number of people, and there's certainly other things like Botox or try and some of these clinics to, and so this is mainly going to be targeted like dermatology and plastic surgery clinics to be used, and and just doing some kind of Google searching, one place kind of mentioned they may be charging like $350 for one application, so there's no real set price, though, so I can't say that that's set in stone, and but it's, it's. It's certainly something that if a patient was suffering from this, they could certainly inquire about, but and so something kind of unique. So with that, that kind of wraps up the new drugs today, I hope you learn something, and with that I'll turn it back over to you Jen.
Speaker 1:Yeah, thank you. Wow, I learned a lot. I feel like I'm on a roller coaster.
Speaker 2:It is kind of a ruin kind of. I know it's a lot.
Speaker 1:Yeah, it's a lot. Yeah, that sweat patch is interesting, you know. I mean, I know that people have tried Botox and you know there's all kinds of things. But oh, these, these dermatology and med spas are just getting all the all the things, aren't they lately?
Speaker 2:You don't try anything, right, yeah?
Speaker 1:right, people spend money on anything. Yeah, and I think I'm just thinking, as you were walking through some things, that the O's out was one of the ones that you know. We talked earlier when we were, when we started out the podcast, about how you learn about things. And then you're like, oh, I don't even know that. And then you know, like, is it like a BMS? Like, was that even a term before, or did the drug company kind of make that up with? I mean, obviously I know there's vasomotor symptoms that are associated with menopause. I know that all too well. Actually, like, is BMS? Like, is that always been kind of a? I just like those commercials came out and I was like, what are they talking about?
Speaker 2:Well, I think it's something that maybe gets used in that world but isn't really brought to light until we see that direct advertising right. Yeah, yeah, it's that direct to consumer advertising, yeah you'll see these different terms pop out and all of a sudden everyone's using it and so you know. But you're right. The first time you hear it you're kind of caught off guard, because maybe you haven't. It's not something that's common term, that's thrown out there.
Speaker 2:So I certainly you know working that my practice is an acute internal medicine and so this isn't something that I'm gonna commonly encounter. I mean, I always find it valuable to be aware of these things because you never know when a patient's gonna come in and they on their home med list. This is on there, and so it's great to have an idea what that is. That you're aware, but not certainly something that I'm gonna commonly encounter in my world, I guess. As far as the practice.
Speaker 2:But you're right though. But you're right. Family friends, I mean, I've been approached there about you know, those types of symptoms, especially if you're wanting to avoid estrogen products. Yeah, yeah, certainly a hot item. Interestingly enough, I did talk to a pharmacist at one of the meetings and they did mention the patient being on it, and they did mention that they did have to stop it because they had a little slight bump in their LFTs and so they were kind of monitoring that closely. I don't know if they were gonna rechallenge or not. We didn't get into that, but that, while that didn't really show up in the short-term trials and it showed up in a small percentage of long-term it. You know, I guess I don't have any direct experience about it, but it does appear to be something that has been at least encountered at one person in practice.
Speaker 1:Yeah, yeah, I found that interesting. Yeah, that's super interesting. And I mean there's always risk, you know, associated with all these, but it is a huge problem. So it's great to have a non-estrogen alternative. So it'll be interesting. You know, just the cost of some of these is so prohibitive. So that's the hard thing with all these new drugs.
Speaker 2:It's like what's the risk versus the benefit? They put a huge price tag on them. Fortunately, you know, if you dig into it, some patients may be eligible for assistance. Again, that's logistical things you had to go through, though, and how much time does everyone have for that, but certainly it's worth pursuing if someone is a good candidate for one of these medications.
Speaker 1:Yeah, yeah. So what's your sense? You know, I do feel like over the last you know few years, I mean, there have obviously been some very novel I'm GLP ones being one of them I mean definite game changers in the market, but in terms of, like the past year or two new drugs to what you're seeing come up in the next, you know 12 to 18 months. You know anything novel, anything that we should be keeping our eye out for.
Speaker 2:Yeah, I was at a Cardiovascular Conference and they were, you know, obviously they're very familiar with their world and doing clinical trials. And one of the products they mentioned that they think is gonna be a real high-ditem in the future and I don't know if this is gonna be in the next year or not, because I haven't seen anything in the immediate future but the factor there's factor 11 inhibitors that are gonna be coming out supposedly, at least based on what they're seeing and at least what they're anticipating. And again, it's hard to speak about the future of medications because you never know what these clinical trials are and what will come up from a safety signal or an efficacy endpoint. But that's one of the agents they kind of mentioned as being on the horizon, that's in phase three clinical trials and that's something definitely to keep on the radar.
Speaker 1:Yeah, that would be huge. Well, and just this whole dementia area too, you know you see the price tag on some of that and whether there's long-term, you know whether you can hold that, you know progression back long-term and you know, like you talked about, with the cost associated with that, but you know that's an area where we need some drugs.
Speaker 2:And I'll tell you we're probably gonna be talking about one of those next year, at least based on what we're seeing in. Nnmab is another one that's coming out, but it's very similar as far as it's kind of concept as far as the previous two, adicandumab and Macanumab. It's gonna work on that amyloid plaque. So we'll see, I guess, is the efficacy gonna be different with that one? I don't know yet, but that is gonna. That was that's gonna be. I think it was anticipated actually late 2023 and I have not read anything about what might be holding that up, but I would expect there at least to be a decision on that sometime in the near future.
Speaker 1:Yeah, yeah, well, getting a lot of scrutiny, obviously after the first one, then hope that you know being approved, not approved, and then taking it off the market. So I'm sure that they're slower to market for some of those, for good reason, but an area where we definitely need some innovation.
Speaker 2:Definitely. And yeah, because there's just no great treatment options. We know that it's hard for families, it's hard for patients, it's been really hard for families to watch that and go through all that and you know I've been personally impacted by that to a family and it's hard, which is no treatment options and so, but the question is, is it the right treatment option? And that, you know, certainly is something that's gonna have to be critically evaluated if that's gonna be the right choice for each individual patient.
Speaker 1:Yeah, yeah, well, that'll be interesting to watch. Thank you so much. This was fun. I even, you know, I've sat through this at expo and I even learned some things a second time around. So lots of information here. As Dr Strain mentioned, if you are a CE plan member, we will have these more in-depth handouts in the learning management system. So when you go to get your credit, you'll see it there as a handout in the course information and so you can look back and you know if you're curious about some of the dosing and you know some of the things we weren't able to get you know so into on just a podcast, you can see that there. So be sure to claim your credit for this episode and, as always, it's great working with you, joe, and thank you again. Thank you so much for being here and for all of our plan members. Have a great week and keep learning. We'll talk soon and thanks a lot.