Six New Key Therapeutic Agents Have Come to Market for the Older Adult Population

Pharmacy Times® interviewed Nana Entsuah, PharmD, Health Sciences Assistant Clinical Professor, Department of Clinical Pharmacy Practice, University of California, Irvine and UCIMC Senior Health Center, on her presentation at the American Society of Consultant Pharmacists (ASCP) 2022 Annual Meeting titled “New Drugs Update.”

During the interview, Entsuah provides an update on 6 new therapeutic agents she will be discussing in her ASCP presentation, as well as the agents’ appropriate use in an older adult population. The therapeutics agents discussed include tapiranof (Vtama; Dermavant Sciences), oteseconazole (Vivjoa; Mycovia Pharmaceuticals), faricimab-svoa (Vabysmo; Genentech USA), daridorexant (Quiviviq; Idorsia Pharmaceuticals), tirzepatide (Mounjaro; Lilly USA), and abrocitinib (Cibinqo; Pfizer).

Pharmacy Times®: What are the new therapeutic agents you will be discussing in your ASCP presentation, and what is the appropriate use for these agents in a geriatric population?

Nana Entsuah: This is really interesting. I'll tell you the specific meds that I'll be talking about here in a second. But I think there are a lot of really exciting new drugs that are coming to market for various indications. It's really—it's always sort of an eye opener when you start to delve into what's coming out, what's on the horizon. So I'm just going to highlight 6 new agents that I'll talk about in my presentation at ASCP, and of course, there are a plethora, there are a lot of agents to choose from. But I think these 6 are very relevant to the geriatric population.

So, the first one that I'll share is called tapiranof. It's indicated for the treatment of plaque psoriasis, specifically within the older adult. We know that there are a lot of changes that happen, even towards our skin integrity, as our patients are aging. So it's kind of nice to know that there are agents that are targeting a lot of the dermatological conditions that our older adult patients might experience. So that's the first one.

So, the second agent is oteseconazole, it's an azole antifungal. Well, that's indicated for recurrent vulvovaginal candidiasis, or VVC. It's particularly for patients who are not of reproductive potential. So in the older adult, that would qualify. But there's a lot of interesting things about this one particular drug. The first, of course, is with it being an azole antifungal, but there's something that sets it apart as compared to the other azole antifungals. I think we'll talk about that later on as the conversation progresses. So that's the second agent.

The third one is faricimab-svoa, which is indicated for macular degeneration and diabetic macular edema. Then there's one that we might be a little bit more familiar with: it's a dual-orexin receptor antagonist or DORA, and it's called daridorexant. There are a lot of information floating around about this one particular agent. As a matter of fact, last night, actually, I saw a direct to consumer advertising about this particular agent. And I thought, ‘Huh, well, I'll be talking about this here in a few weeks.’ So that was nice to see and hear what was being shared in the advertisement or dairy direction.

The last 2 that I'll share in my presentation are tirzepatide—I’m sure that sounds familiar to a lot of our listeners—which is a dual target agent indicated for diabetes, and then the last one is abrocitinib, which is a new agent that's been proposed for the use of atopic dermatitis. So again, going back to some other dermatologic conditions that are older adult populations, and the population as a whole, might face, this is another one targeting dermatitis. So those are the 6 agents that I'll be discussing and what they're indicated for.

Pharmacy Times®: What are the most important adverse events and risks for these new drugs in a geriatric population, and are there any specific considerations for these drugs in this population versus a younger population?

Nana Entsuah: Yeah, this is an excellent question. It's an excellent question because I feel like it's—with a lot of new agents, sometimes, unfortunately, clinical trials don't always include an adequate amount of older populations, so we don't always know exactly what the effect within the older adult population will be with a lot of these agents. So that's a problem that I face, of course, when learning about these and putting these presentations together.

So I'll start off by saying that some of the trials that assess the appropriateness in some of these new agents, they observed no overall differences, and that was no overall differences in efficacy and safety, nor in tolerability within the older adult subjects as compared to their younger adult subjects in the clinical trials, and examples of that would be tapiranof, and that's not too surprising, because, again, it's a topical agent for psoriasis and faricimab-svoa. But others like oteseconazole, again, that's an azole antifungal, the daridorexant or DORA, and then tirzepatide—those ones did see some adverse effects that would, I suppose, require some caution in the use in the older adult.

The clinical trial for abrocitinib didn't have the sufficient number of patients over the age of 65. Remember, I talked about that in the beginning, that some of these clinical trials don't have an adequate sample size of older adult patients for us to really determine whether there's a difference.

So now I'll just kind of briefly touch on each of the agents that I'll discuss and some of the key adverse effects that we're seeing, starting with tapiranof. So, for that one, the most notable adverse effects within the older adult population were folliculitis, nasal pharyngitis, and dermatitis, again, considering its use and its indication and application, it's topical. So not too much of a surprise there. For oteseconazole, it was mainly nausea, headaches, and that included migraines and sinus headaches as well.

Quickly going through the other ones—for faricimab-svoa, most of the adverse effects that were noticed were the—I suppose the more severe one was the retinal detachment, which was likely due to improper aseptic technique when administering the drug. It's an injection that's administered into the cornea. So when the aseptic techniques aren't properly followed, the researchers did observe some incidences of retinal detachment, in addition to an increase in intraocular pressure, which was seen within about, I want to say, 30 to 60 minutes of injection, they saw these changes in interocular pressure, as well as the likelihood of retinal detachment. So these are very, very serious adverse effects, of course, but the researchers as well as the manufacturers have some recommendations in place for monitoring and managing this in the case that it did happen.

So, not surprisingly, for daridorexant, which is our agent indicated for insomnia, most of the adverse effects that we're seeing were CNS related. So your somnolence, dizziness, fatigue, and even daytime impairment because, again, for what is indicated for and what it does—of note, I do want to highlight that there was an observation of worsening depression and suicidal ideation. So that's something to, of course, be very cautious of in our elderly population, who already might be a little bit more prone to some of these CNS changes and CNS adverse effects.

For tirzepatide, again, not so much of a difference considering it's a dual target. It's a GLP-1 receptor agonist, so the risk of thyroid tumors and pancreatitis occurred, again, not very surprisingly from what we know of that being a class effect.

Then lastly, for abrocitinib, there is a black box warning for thyroid C-cell tumors. So some of the other adverse effects that were observed were abdominal pain, nausea, an increased likelihood of thrombocytopenia, especially within the elderly population. So that's something that I want to highlight that within the study, although they didn't have a large number of elderly patients over the ages of 65, there was a greater incidence of thrombocytopenia within this population. So the researchers did note that there was a larger population of the patients over 65 that actually dropped out of the studies as compared to the younger population.

So I know that was a lot of information that I just threw out, but it's very important information too considering the patient population that we serve, and the things that we should be sort of clued in on when it comes to adverse effects within the population.

Pharmacy Times®: How do these new drugs compare to comparable older medications on the market, and are there any notable advantages or disadvantages for use of one over the other?

Nana Entsuah: I think, before I go into the specifics of each of the agents, I think one thing to touch on what I mentioned earlier is how exciting it is to see new agents come to the market. And I think that the agents that we have now, of course, lay the foundation, for us to know, ‘Okay, this worked quite well, but there's some opportunity to maybe improve it by looking at it from this side,’ and sort of the scientific method that we as health care providers, so it's the lens that we kind of have when assessing new medications.

So I love that you're giving the opportunity for us to sort of a comparison and contrast between the agents that we have that are new and what's currently on the market. So let's get into it.

The first one that I'll talk about is tapiranof, and actually, very excitingly, is that it's the first in its class. There are current other treatments for psoriasis that are mostly over the counter. So we have your usual over the counter hydration and emollients, you also have your corticosteroids and topical vitamin D analogues, but there are none of them that mechanistically compare to tapiranof, so that's what sort of sets it apart with the other agents that are utilized for treatment of psoriasis.

Secondly, oteseconazole, I mentioned earlier on that it is an azole antifungal, which are not new. We've had azole antifungals around for a very long time, but what makes this one particularly interesting is that the literature showed that oteseconazole, on average, was about 40 times more potent than fluconazole, which has been the standard treatment, if you will, for RVVC. So it does offer an alternative for our patients that either have an intolerance to fluconazole, or maybe it just didn't quite work well enough for them—maybe an allergy, or just because it seemed to not be efficacious, but the idea that oteseconazole is about 40 times more potent, that's pretty significant.

Another thing about this, comparing it to other azoles is that the research show that there's a potential that it might have fewer adverse effects from what we know of it so far in drug-drug interactions compared to the other azoles. For reference, for those that are not familiar, azole antifungals are notorious for having a significant amount of drug-drug interactions that I could list, but it would take me a very long time to talk about all the medications that have direct-direct interactions with azoles. But it seems like the ones that had been noticed for oteseconazole right now is rosuvastatin. For the sake of time, we can't go into all the detail mechanistically as to how that drug-drug interaction manifests or why it exists, but it is important to note that oteseconazole seemingly has less potential for drug-drug interactions, and fewer adverse drug events than some of the others also on the market. So that's it for oteseconazole.

For faricimab-svoa, there are other agents that mechanistically work in the same way as the [vascular endothelial growth factor (VEGF) inhibitors]. But what's interesting about the faricimab-svoa is that it's both a VEGF as well as angiopoietin-2 inhibitor, so it targets both of them, not just the VEGF. And that's what makes it unique.

For daridorexant, again, it's part of our DORAs, so not new in terms of the treatment of insomnia, but I guess I can mention some of the other insomnia treatment options that are out there right now: Your melatonin receptor agonist or histamine receptor antagonist, and, of course—what we frown upon in the geriatric world are Z-hypnotics, for the treatment of insomnia. But I do want to note that their direction has a shorter half-life as compared to some of the other DORAs, which makes it a little bit more favorable. So that half-life is about 8 hours or so.

For tirzepatide, it's also novel, in a sense, because it has the 2 targets, it's a dual target. But right now, there's very limited data on it's use, especially for the older adult. I believe that in the pool of the clinical trials, there are only about 30% of the subjects that were treated who are 65 years and above and of those only about 4% were actually 75 years or older. So it warrants a little bit of caution, a little bit of pause when considering the data that we have to support its use in the older adult.

Then lastly, abrocitinib—its efficacy is comparable to some of the agents that are used also for severe refractory atopic dermatitis, such as like cyclosporine, methotrexate, azathioprine, and your systemic corticosteroids, and, I'm happy to go into some of those differences, but I think those are the key highlights that I want to share in terms of how these newer agents compare with some of the older medications, if you will, on the market used for the same treatment.

Pharmacy Times®: What is the pharmacist’s role in making recommendations regarding comparable medications for this patient population?

Nana Entsuah: Well, I think what really sets pharmacists apart from our other health care provider counterpart is our sort of unique and extensive training. I want to really take time now I suppose to appreciate other members of the health care team—our nursing, physicians, and others. They're all key players when it comes to taking care of the whole patient. But the pharmacist in particular, we have the knowledge to critically assess literature, and also determine the appropriateness of a particular medication for use within a specific population.

In my case, in the geriatric population based off of my training and my specialty, we know already that geriatric populations are vulnerable, due to some age-related changes that occur when thinking about things like pharmacokinetics and pharmacodynamics. And our role, my role as a geriatric pharmacist, is to critically assess the literature—see what data is out there, given the patient information that I know about my patients, the snapshot, if you will, oftentimes the snapshot picture that I have about a patient, knowing what their disease is, knowing what their history is, my job is to analyze and assess the literature, and use that information to do as best as I can to individualize the drug therapy and make the best recommendation for the patient.

So I suppose, to answer your question, my role is to use my expertise about medications, that's what I was trained on, to assess the use of medications and know everything that I can about a specific medication and how it works in the body, how the body responds to having this medication in there, and especially how does all that information translate to it being used in the older adult, and use that to sort of shape and guide the recommendations that I make, which I think is an honor. As pharmacists we have the title of being the most accessible health care provider, and it's something that I personally don't take lightly. It's an honor, but it's an honor that we've earned through the care that we've provided for our patients. So I think we just have to sort of capitalize on that and continue providing the best care that we can, and really stand on our level of expertise and expand as best as we can to take care of the patients that we're tasked to serve.