The first self-administered biosimilars for dermatology have come to market, bringing along a number of questions for patients, prescribers, pharmacists, and others. TJ Chao, MPAS, PA-C and Leigh Ann Pansch, MSN, FNP-BC, DCNP break through the noise to explain biosimilars, interchangeability, and implications for patient care. Plus, hear from Hilary Baldwin, MD, about giving great presentations and Adam Friedman, MD sweats the details of hyperhidrosis diagnosis.
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The first self-administered biosimilars for dermatology have come to market, bringing along a number of questions for patients, prescribers, pharmacists, and others. TJ Chao, MPAS, PA-C and Leigh Ann Pansch, MSN, FNP-BC, DCNP break through the noise to explain biosimilars, interchangeability, and implications for patient care. Plus, hear from Hilary Baldwin, MD, about giving great presentations and Adam Friedman, MD sweats the details of hyperhidrosis diagnosis.
Like what you're hearing? Have a topic you want to hear more about? Hit us up and spread the word on Instagram!
Speaker 1: Welcome to the Dermalorian™ Podcast from the Dermatology Education Foundation. The Dermalorian podcast series is an independent educational program made possible with support from UCB.
This summer, the market welcomed the first patient, administered biosimilars for dermatologic indications. What are biosimilars and how will they affect patient care? In a recent Dermalorian webinar, dermatology physician assistant TJ Chow and dermatology nurse practitioner Leigh Ann Pansch sorted through the details.
Speaker 2: Now, in reality, we could have used biosimilars in dermatology as early as 2016 if we were using the biosimilars for Remicade. Now, some of us may have used those. A lot of us probably did not use those. So right now is we're having a blossoming of new products on the market. On Monday, I received my first request from a pharmacy for a patient to switch from Humira to a biosimilar. My patient today, after several days of discussion, decided to go ahead and stay with the products that were being offered by the company. I tried to convince the patient to stay on Humira that he would be covered by AbbVie, but the patient decided, so we actually had to make a decision between two products and he and I made the decision to go with had Lima simply because it's got the low and high concentrations that Humira have, and it also will soon have what's called interchangeability designation. Long ago, I started practicing before biologics. I started practicing in 2000. We had no products, nothing like this available, and now so much time has passed that the government in 2009 decided we have these amazing drugs, but they are expensive and they're a burden on the healthcare system. And when they created the Affordable Care Act, they created the Biologics Price and Competition and Innovation Act, which included the emergence of biosimilars.
Speaker 3: I think we all are certainly familiar with the Affordable Care Act, and as TJ mentioned, this innovation act was passed. We're going to get into where the cost savings is. The research studies for biosimilar medications are really very, very vastly different than what we're used to in terms of these double blind placebo controlled studies with sort of two pivotals at minimum. But none of us are disputing the fact that these have really changed how we practice in the field of dermatology. I think this is sort of where we want to start. What's the difference? Why aren't these medications called generic? Well, it's because they're alive. And so a couple of key differences here between what we consider to be a biologic and what we consider to be a biosimilar. We're talking about a biologic. Obviously, we have these large molecule proteins. We understand that these are live medications.
Speaker 3: This is why they're refrigerated. We've got cells. We've got tissues. These are isolated from natural sources and that we are mass producing this at labs. In addition, we talk about a biosimilar medication. It's important that we understand that in order to be classified as a biosimilar, we do not have any clinically meaningful differences. So how do we prove this? Well, we prove this by sort of ruling out or sort of looking at pairings of safety, purity, and potency. And I want to pause right here. I want to talk about in the world of generics, everybody, most of us understand this P value concept where when we're talking about a generic and its original branded medication and a generic, we understand this concept of wanting to make for sure that that generic medication is not statistically significantly different. And so we're looking at this P value of less than 0.04.
Speaker 3: Well, in this case, when we talk about a biosimilar, which is not a generic because it's a live molecule, we understand that we can do that by sort of proving that it has no clinically meaningful differences from its originator medication that's branded. So trucking right along. What can I expect? In essence, if we're saying that this is an approved biosimilar medication within our market, we understand we've got live sources of cells and tissues. It's got to be the same strength, the same dosage, the potential treatment benefits, but also potential side effects. And so let's just pause here and let's just look at the world of potential recognizing that if we have a biosimilar medication already deemed not clinically different, not clinically meaningfully different from that original medication, we understand that it's not the original. And so potentially here we have a medication that may in fact offer some clinical benefit, but in addition, there is concern that potentially we might see some side effects.
Speaker 2: So the FDA puts great focus on the testing of these biosimilar medications. The focus though, is not on what you would traditionally think as a clinical trial. In fact, there's really, it's not at all like a typical clinical trial would be done. Essentially, what the FDA is really focusing on and trying to prove is the structural and functional characteristics of these drugs. These biosimilars are the same as its originator product. And so what that means is they're not testing outcomes necessarily. They're not testing long-term PASI results. They're not looking at safety data long-term necessarily. They're really initially focusing on structure and function. So what that entails is a little bit of efficacy, a little bit of safety, but mainly pharmacokinetics and pharmacodynamics. So the focus of this biosimilar study is cost. Now, in my opinion, one does have to question the utility of biosimilars in dermatology.
Speaker 2: To date, we really haven't, A lot of us have not used Inflectra or Renflexis, which are the biosimilars for infliximab. But however, we more commonly use the drug Humira. So likely many of us will see some exposure to these biosimilars. The question is how many patients are really going to still be getting the adalimumab molecule in the next few years? The market share is already down for psoriasis. Currently, the market share is hidradenitis suppurativa, but with new agents and new mechanisms coming, that is a question surrounding the utility of these biosimilars in dermatology. With that said, these biosimilars are going to have a huge impact in other specialties, especially rheumatology, where many of those prescribers are still utilizing the same drugs. We in dermatology were using 15 years ago. So like we said earlier, the biosimilar studies really are about structure and function.
Speaker 2: They want to show that the drugs are similar. The biosimilar has similarity to the originator drug. Essentially what's happening here is that these new drugs are riding on the coattails of their predecessors. Now, there's a benefit to them for that where they don't have to do the more costly, the more extensive studies, clinical trials like were done with the originators like Remicade and Humira. So there's a cost savings here to not only the company, but then they pass that cost savings hopefully onto the system and onto the patients. So biosimilar studies are not powered for superiority. They're not trying to say that they're superior. They want to show that they are equal to the product that's already on the market. And the F D A does not want superiority shown. They want a similar outcome shown.
Speaker 3: So another key concept here is extrapolation. And so again, how does this all work? We're looking at all of the summation of evidence here in various clinical trials for these biosimilars and then comparing it to our originator medication. So it's important that we understand that we're talking big umbrella here in terms of that F D A view when they go to approve these medications, pharmacokinetics and pharmacodynamic data. Remember pharmacokinetics, how does this medication work? Pharmacodynamics, what does this drug do to this patient? Those are a little bit harder. Certainly we're looking at safety studies, we're looking at immunogenicity and efficacy data as well. And interestingly enough, one of the key drivers in the world of adalimumab comparisons are even what we know to be true in our originator studies, which are these neutralizing antibodies. We talk about neutralizing antibodies in these studies, the F D A said, I wouldn't know what your rate of neutralizing antibodies are in your clinical study for your biosimilar, and how does this compare to its originator, the Humira product?
Speaker 3: So this is an example of a concept that I think is sort of a plus. So we have the world of biosimilars. I think we've sort of made that clear. We're all about structural function. There's no clinically meaningful difference. But now we're going to incept interject a concept called interchangeability. What's interchangeability? Well, I got to be honest, guys. It scares me. Bottom line, this interchangeability is a designation that is in addition. So first, typically that company's going to go for biosimilar approval, but then they may in fact go to this interchangeability designation, and that means more study. But what interchangeable means is that it can be substituted for reference product at a pharmacy without additional approvals from the prescriber. And so here's your plug to really know your state laws in terms of what is legal in your state in terms of does the pharmacy have to alert you to a change or not?
Speaker 3: I don't know about you, but I don't do a lot of infusions in my clinic. I don't really have to. We have great drugs. And so I do have a couple patients on biosimilars, but I typically turf those two infusion centers. And so I might not know what is the difference here? How is my patient responding? But in the world of biosimilars, currently we are talking about the 40 milligram dose of adalimumab, and we have several that are already on market, and we even as TJ mentioned, have some that have been rendered or designated interchangeable. What does that mean? How do we do that? Well, again, as I mentioned, there are some switching studies going on.
Speaker 2: Once we get the notification from the pharmacy that we can switch the patient or not switch the patient, what happens then? Well, you as a prescriber right now have a choice right now. I was given a choice this week and I was very thankful that I received the letter notifying that I was being given an option. Automatic substitution is something that can occur. Now, going back to what Leanne was saying, we will have to see how this is going to play out in the real world. But when a drug is rendered or designated as interchangeable, once they do those studies, the pharmacist then can switch the patient to a biosimilar without notifying you right now, they have to notify you. They have to get permission if it's not interchangeable, and you essentially have to write a prescription for the new product. With interchangeability, there's automatic substitution that can occur without any notification from the pharmacy to your office.
Speaker 1: We'll learn more about the practical implications of Bioequivalents ahead, but first, our Dermalorian™ Derm Decoder in which Hillary Baldwin provides tips on giving better presentations. What do the most successful speakers do that sets them apart?
Speaker 4: Well, they certainly know every aspect of their talk, the subject itself, but also themselves, their audience and the room. They prepare very well for the performance. All of the people that you've heard at this conference and in these lectures, all of them rehearsed these talks numerous times before delivering them, even though they've done it 10 or 15 times before, they rehearsed it again and they practice smooth transitions from the beginning to the end. This should be a story. Every talk should be a story that starts at the very beginning and ends at the end with a nice smooth transition all the way through so they know their subject and of course their slides and they know them cold. If the electricity went out, they would be able to give the talk virtually, verbatim.
Speaker 4: They know all of the details of their topic, and sometimes the backstory is a little bit more interesting than the story itself. Let me give you an example of this. I've had to do a lot of talks over my time where we're talking about toll-like receptors. Where did that word come from? Why do we call it a toll-like receptor? Well, the story goes that when toll-like receptors were first being discussed in a group of scientists with a group of scientists in Germany, they all were absolutely amazed at these receptors. And the word for cool in German is apparently toll. And they were sitting there going, wow, toll toll. And that's how toll-like receptors got named. So it's a cute little backstory, right, that you can share in the middle of having to talk about something quite dull, like toll-like receptors. An excellent speaker has also read every reference and they remember the details. Perhaps they've even brought a copy of it with them.
Speaker 1: Those were some helpful tips from Dr. Baldwin shared at Derm 2022. Now, let's get back to the conversation about biosimilars.
Speaker 2: The question is, we know that there's going to be a benefit to the companies that bring these products. How is that benefit going to be translated to the patient? And an interesting question I also have is if the company that creates the originator biologic gives the patient the drug either at a zero copay or a $5 copay, what really could the difference or financial benefit be or the savings be for the patient on these medications? So I think it's a very interesting subject and topic that we'll have to talk about in the future. Essentially, these drugs have to have the same m o a, the same route of administration, the same dosage forms, and the same dosage strengths. Now, there is some variation.
Speaker 3: There is a concern that in certain states know your laws, a pharmacist could potentially change that originator prescription to a biosimilar that has been deemed interchangeable. And again, this interchangeability designation means that we have the same clinical outcome expected from that originator medication. I think another thing to really consider here is to date we have the most experience with infliximab, but infliximab is an infusion. The patient wouldn't potentially know if they were getting the biosimilar or the originator medication if they were getting an infusion. But in the world of injections, we recognize that these devices for injections are typically patented. These companies own these devices. And so we may in fact have some patients who are feeling very specific or I'm really comfortable with this device, but I might not like that device for that company. And so it is something to keep in mind.
Speaker 3: I don't know about you, TJ, but I think I am forever grateful for the National Psoriasis Foundation. I think they've done an incredible job at really advocating for our patients in ways that we just don't have the power ability to do as providers. In that sense, I will tell you that they produced a position statement. I want you to recognize that this is not a law. This is a simple recommendation. I think that there's some weight here because it does come from a very well-respected organization, the NPF but they are recommending when it comes to these biosimilars and specifically the substitution of biosimilars, that there is some governance surrounding that substitution. And so number one, if a biosimilar has been designated by our FDA as approved and interchangeable, then the biologic has to be approved and interchangeable for that specific indicated use.
Speaker 3: What does that mean? Well, that means if that biologic has been approved as to treat psoriasis but not psoriatic arthritis or psoriasis, but not HS, then I can't interchange it at the pharmacy level. So just something to keep in mind. Recommendation number two, this biosimilar, it's got to have a unique non-proprietary name. Recommendation number three, we have to follow the same route of administration and the same dosage form as that originator. Product recommendation. Number four, the pharmacist has to notify the prescriber in writing or electronically with this intention to substitute at least 24 hours prior to the substitution. Again, I want to mention this is not a law. Know your state laws know what the rules are within your state, but again, NPF is recommending that they have to notify you in advance. Let's hope they do that. Recommendation number five, we must have explicit permission from the prescriber within 24 hours of that original prescription to be filled.
Speaker 3: And recommendation number six, the patient has to be notified and educated about this biosimilar substitution at the time of sale. Don't want to be that pharmacist because I think that's going to take a little bit longer than the usual just sign here. And number seven, upon notification of a substitution, the pharmacy and the prescriber, we have to maintain a permanent record in the medical record of that substitution. And so within our practice, we are definitely looking at this in terms of how do we want to track this. But definitely have a plan in place and make sure that you are supporting staff and those, I call them my right hand and left hand, but make sure they know what you want to do in order to track.
Speaker 2: Great job, Leanne. I could have done it better. Those were a lot of recommendations and I really hope that the companies will adhere to those. So we'll have to see how that all plays out in the market. So biosimilars are highly similar to and have no clinical meaningful differences from the originator biologic. The products that have been F D A approved previously biosimilar development must demonstrate the structure and function of the biosimilar is highly similar to the reference product. So again, pharmacokinetics, pharmacodynamics, pharmacodynamics, efficacy, safety. But the cost savings really for these companies is in the studies where they don't have to conduct extensive models and they don't have to have long-term data out for years in monitoring these products. So there's cost savings, and again, we'll see if those cost savings are translated to the public biosimilar medications. Use this totality of evidence to affirm that there are no clinical meaningful differences in terms of safety, purity, potency, and clinical benefit. And biosimilar assessments include analytical pk, which is pharmacokinetics, pharmacodynamics immunogenicity, making sure that there's no anti-drug antibody development or if there is, at what level is that as compared to the originator. And they also will look at comparative clinical studies as needed.
Speaker 1: It sounds like patients and prescribers will be sweating a lot of details. Speaking of in this edition's, dermal Lian clinical clip, Dr. Adam Friedman offers insights on the diagnosis and classification of hyperhidrosis.
Speaker 5: So let's delineate between primary and secondary hyperhidrosis. Primary hyperhidrosis, you need at least two of the following early onset. Now, I will say some patients may not really appreciate that what they notice as excessive sweating when they're in their childhood, that that was hyperhidrosis. It should be bilateral and symmetric impairs daily activities. That's where those questions certainly come in. For me, cessation during sleep is one of the big ones. So you could sweat when you're sleeping. If you, you're in a room that's 95 degrees undercovers, yeah, you're going to sweat. But that excessive sweating noted during the day should taper off at night. Family history certainly also I think is something to ask because I think there's a good amount of data showing that there is a genetic predilection. We don't know what it is yet, but that there is certainly a connection there. Secondary, a little different, usually caused by some underlying issue, maybe a side effect of medication. Underlying medical problem comes out of nowhere, sudden onset persists night and day. So those are the kind of key distinguishing clinical features. You can also have some localized forms of hyperhidrosis associated maybe with anxiety disorders and, maybe a nerve injury, for example, like Frey syndrome, whereas someone is chewing or eating food, you get this kind of gustatory associated focal hyperhidrosis at the side of the face. So these are kind of unique forms that I guess technically would be idiopathic. Sometimes we consider them primary, sometimes they're secondary to underlying trauma.
Speaker 1: That brings us to the end of another Dermalorian podcast. The Dermalorian podcast series is an independent educational program made possible with support from UCB. Catch up on previous episodes and hear new content wherever you stream podcasts. Thank you for joining us.
*Transcription errors may result in inaccuracies.