FDA ends GLP-1 compounding for semaglutide, tirzepatide

Transcript - FDA ends GLP-1 compounding for semaglutide, tirzepatide

Alivia Kaylor: Welcome back to Healthcare Strategies. I'm your host, Alivia Kaylor, Senior Editor of Pharma Life Sciences. And today I'm joined by Executive Editor, Sara Heath, to talk through what the FDA's latest move to end the GLP-1 shortage officially means for patients who've been using compounded versions of these drugs. Sara, thank you so much for joining me today.

Sara Heath: Yeah, of course. Thanks for having me. You know, I'm not a scientist or anything, but I do have some insights about what this could all mean for the patient. So, I'm excited to chat, and I'm excited to learn a little bit. You have a lot more expertise in some of the science and the policy-making that is behind a lot of this.

Kaylor: Well, and that's why I have you here. I'm actually really excited to hear what you have to say on behalf of the patients because this change is definitely going to be something that impacts a lot of people. They may not realize it, unfortunately.

Let's just go ahead and start with the shortage and how it's ending. Currently, GLP-1 receptor agonists, depend on two APIs, active pharmaceutical ingredients, if you will. Those are semaglutide and tirzepatide. The FDA recently took these off the national drug shortage list. And so that officially ends the temporary permissions that allowed compounding pharmacies and outsourcing facilities to make the different versions of these drugs.

Let's just break down the dates for that since they're different. For semaglutide, small compounding pharmacies -- so we're talking like your 503As -- they had to stop making it by April 22nd. But for larger outsourcing facilities -- those are more like your 503Bs -- they have until May 22nd.

Right now, you're pretty much only able to access, if you're a patient, semaglutide through these compounding facilities because tirzepatide deadlines were much earlier, February 18th and March 19th, respectively. This means compounding facilities can't legally sell compound versions of these drugs unless they're approved by the FDA. Really, that means the only compounding facilities that are able to make compounded versions of this drug after May 22nd are your 503As because those are your smaller facilities. Those are going to be your smaller individualized doses. Those are literally the only ones that can do it. 503Bs can no longer, after those dates that I just mentioned.

Heath: Yeah, and I think this is notable because a lot of patients actually went the compounding route to get a GLP-1 because they couldn't get the name brand version of the drug for numerous different reasons. You know, either their insurance didn't allow for it. They might not have been able to afford it regardless of insurance coverage. So, with the compounding options going away, patients are going to be kind of pushed back to having to go through that more traditional healthcare process of getting their provider to write the prescription, get their insurance to cover it. You know, there are numerous hurdles involved: prior authorizations, insurance delays. All of those things that we in the industry are super familiar with. And ultimately, this creates a real concern about whether the system can handle this influx of patients who are trying to access the branded versions of the drugs.

So yeah, the shortage isn't necessarily being caused by a lack of active ingredients, but just a lack of injector pens. And I don't know if you wanted to kind of talk a little bit more about that.

Kaylor: Yeah, definitely, Sara. And I do want to make note for everybody in our audience that the shortage is not due to a lack of our active ingredients, right? It's not due to a shortage of semaglutide or tirzepatide. It's actually a lack of the injector pens that the active ingredients are actually in.

It's kind of surprising because -- in other countries -- the injector pens are not part of these drugs. They actually get vials, and the dosing is different. If America was not operating on this injector pen, I'm not sure if this shortage would have ever been reached. Yeah, and it's not the active ingredients that are expensive. So that's not the limiting reagent, and I just want everyone to be aware of that. These drugs, they're not expensive. How we are administering them, those devices.

Heath: Okay. Yeah, that's really interesting.

Kaylor: It is not that they are expensive or take longer to create.

Heath: Yeah, that makes a lot of sense. And I didn't know that in such clear statements. I'm sure I've read it and been like, yeah. But hearing you kind of just clearly state it that way makes a lot of sense. I don't know if we should move into talking a little bit more about what even a compounded GLP-1 is. I'd love to tap into your expertise on that.

Kaylor: Yeah, definitely. Compounded GLPs -- these are versions of the popular diabetes or weight loss drugs, like Ozempic and Wegovy. Those are your semaglutides, manufactured by Novo Nordisk. Then, we have Mounjaro and Zepbound. That's your tirzepatide, produced by Eli Lilly.

Those versions are being made by compounding pharmacies. Well, right now, only semaglutide. Those are basically customized formulations that aren't FDA-approved, but were allowed during the shortage. So, when the FDA declared that we were in a national shortage, these 503As and 503B pharmacies -- I'll get into later exactly what these mean -- were able to then produce these drugs to meet the need. But now that the shortage is ending, they are no longer able to create these drugs.

Heath: Can you talk about the different types of compounding pharmacies? I know that there are specific ones, but I'd love to hear what makes them distinct.

Kaylor: Yeah, so like I said, there are two types: 503A and 503B. For 503As, I like to remember it like this -- 503A, they're more abundant. There's more of them, but they're smaller, okay? These are the pharmacies that are actually going to make custom-tailored medications for specific patients based on prescriptions. Say you have a child who is allergic to some inactive ingredient within their antibiotic, right?

You would have a compounding facility then remove that inactive ingredient for that patient so that they are able to take it. Or if there is a certain type of drug that is only in a tablet form, but someone's unable to swallow a pill. Then, you could have it made into an injectable version.

Those are more personalized changes based on -- you know -- your own personal health information.

503Bs, those are going to be your larger facilities. Both of these pharmacies follow rules. But specifically, 503As follow more of the state rules, whereas 503Bs follow more federal. You could think of it like 503As are more personal, while 503Bs are like small factories. They are able to meet greater demand.

With those bigger batches, those 503Bs -- I just now thought of that, bigger batches, 503B, bigger batches -- sell primarily to healthcare facilities, and then they can meet the manufacturing demands through that. For this specific talk, most of these GLP1s are being manufactured through 503Bs. That's the pharmacy that's losing the ability to create the compounded [versions], which is why it's such a big deal.

Heath: Yeah, and I think when we zoom out from not just the pharmaceutical industry that might be making these compounded versions of the drugs, but now onto the patients who might be taking it. That's a pretty significant impact. There are some estimates putting it into the millions of patients who've taken compounded versions of this drug. KFF has done a lot of surveying about GLP-1s and where patients are getting it.

And it's, you know, not just the doctor or those specialists writing a prescription, but it's people getting them online, where a lot of those online pharmacies were touting those compounded versions. They're getting them from med spas. Some of them are getting them from, you know, unspecified sources. So, these are folks who are really getting these more customized or not customized, who are getting these compounded versions of the medications. Now, in terms of like who, what type of patient is accessing these compounded versions of the medications, you know, I don't have a ton of great data about who's accessing it, but I do have some data about who is not accessing the reference drug, which gives you an inverse picture, right?

The folks who aren't accessing the reference drug, which is the expensive version of the medicine. Those are your Black, Asian, Hispanic patients and your low-income patients. Those are the people who, if they're going to get a GLP-1, are a lot more likely to get that compounded version. This is giving us a lot of insights into who's going to be affected by these changes. And ultimately, we need to think about how patients are learning about these changes because these are the people who are taking the medicine or not taking the medicine, as we might get to later in our conversation.

Kaylor: Right. And honestly, I'd be curious to know just how many patients are taking these compounded versions. Do they realize that they are going away or have gone away? That's the scary part, in my opinion, because then, where are they turning to? Like you said, med spas.

Well, something that we have to consider with compounding drugs -- like, yes, we primarily relied on overseas for Chinese APIs because they don't, I mean, let's be honest, they don't really recognize our patents the way we do here. They're going to be getting a product from overseas. Sure, it could be from a manufacturing facility that is FDA registered, but how do we know that?

Heath: Yep. And I think what makes this conversation even scarier is that we don't know what we don't know. So, you raised the question of how many patients know that this change is coming.

I hope maybe there are some large think tanks that might be surveying public awareness of these changes, but it's only a few months into the ending of the shortages, so I don't think that we quite have our hands on that data yet, but we're really hoping that there is enough public messaging so that patients are aware they were taking a compounded version.

There aren't, you know, those FDA-registered facilities making those anymore because they're not allowed to. So, anything else that I could get compounded isn't safe. That's the idea. Do I think that's happening? I can't say for sure. And I am sadly a little bit pessimistic. You know, there could be a lack of communication between prescribers and pharmacies with patients.

It's also just kind of a difficult concept to explain. I mean, we've spent 15 minutes talking about what a compound is, the different types of pharmacies, and all these regulations. So that's a lot for your typical person to be able to absorb. Right. Yeah. And especially, I mean, what is it like? Health literacy is pretty low in this country, so being able to wrap our heads around what these medications are is a pretty tall order for patients. It's definitely going to necessitate providers to have these open relationships with patients to know what they've been taking so that they can further advise them, so that they can be really safe with what they're putting into their bodies. I also think that this creates a big risk in interrupting medication, if a patient can't just refill a compounded version that no longer is allowed to be made. While we've been talking a little bit about counterfeit products, there's also just this question of the patients no longer take it and what happens then. So yeah, there's definitely a lot of risk about how much patients know about this situation and how much guidance they're getting about how to move forward from here.

Kaylor: Yeah, I just feel like it's putting patients in a position where they can easily find a product that they should not be putting inside their body. Like you said. And I think, you know, we should talk about maybe what happens next for these patients, right? Let's say they were on compounded versions, and now they have to switch whether they were on these products for diabetes or weight loss, they're going to have to switch to FDA-branded, FDA-approved brands like Wegovy and Zepbound for weight loss and Ozempic and Mounjaro for managing diabetes. But like you said, it's not as simple as just picking up a prescription, and I think the biggest glaring issue here is cost or lack of insurance. But I also think that something to consider here, too, is that a lot of people bypassed their insurance to even go for these compounded versions. I'm not sure if all these patients asked their insurance companies, like, "hey, here's my A1C; do I qualify?" before they went for a cheaper version. Because I know some of these people are paying out of pocket for compounded versions. They're paying out of pocket anywhere from $400–600 per month.

Insurance coverage could get you something like $100 or less per month, you know? I'd be remiss if I didn't say that anyone who's considering these drugs, whether it be for diabetes or weight loss, should check with their insurance companies to see if it's covered or if something similar -- whether it be Eli Lilly's version or a Novo Nordisk version -- is covered under their policy. If not, then I think that's when you need to explore alternate avenues, but again, these avenues are disappearing.

Heath: Yeah, that's a really good point that you bring up. How many people raised their hand and said, "I have a medical issue." Doctor puts in for the prescription for, you know, Wegovy, Zepbound, Ozempic or Mounjaro. Then it got denied, and that's what led them to the compounded version? Or how many people were like, "I'm on a weight loss journey. I want a GLP-1. I'm going to Google, 'Where can I get a GLP-1?'" And then, they got it. 

Kaylor: And I understand wanting that now, right? Without the prior auth, without going to the doctor to get the approval, I understand that 100%.

Heath: Mm-hmm. Yep. Yeah, for sure. Especially, you know, first off, just like the personal desire to do that, but then also is there necessarily an understanding that these medicines are prescription? Who knows? That might've also been part of what prompted, "I'm just going to go online and get this," you know?

Kaylor: Right, and that may be derived from patients not understanding how to qualify for these drugs, whether it be for diabetes or weight loss. And then I'm sure you just have discouraged patients who wouldn't qualify otherwise, but they don't see any other avenue to losing that weight, right? But I think something that we haven't really talked a whole lot about, but like, I'm not sure if it really is a problem. Like for diabetes, if your insurance is covering it, then losing the compounded versions really isn't a problem for you because you do get coverage, and it is less expensive. That's why this conversation is a little more geared toward the weight loss, obesity crowd, because they're the ones who are paying more out of pocket.

Heath: Yeah, yeah, because I know Medicare isn't covering it for weight loss and obesity. Whether commercial or employer-sponsored insurance is covering it for those indications is wicked murky, or very murky as well. I'll take the Boston out of it. But so, that's definitely like an added layer to it.

This gets back to some conversations that I had with healthcare providers a while ago. Frankly, we were talking about care management strategies for patients who were on these medications, but we were talking about how the concept of weight loss in America has been so commercialized. It's this moral failing that it is the individual's responsibility to fix.

And so you go out and purchase this medicine that's going to be the fix, as opposed to a holistic, whole-patient, patient-centered view of how to support weight loss, which, to be very clear, medical intervention is an arm of that approach. But I think it gets to the idea of going out and purchasing the medicine that is the fix. We have people who are running into some of these very common roadblocks, including prior auths and insurance denials. We're going to have a lot of patients who are suddenly helpless and need to have a provider or someone in the healthcare system who's able to help them, be like, "Actually, here's the more ideal road to accomplishing this goal that you have."

Kaylor: Absolutely. And I will add that I know it sucks to see these compounded versions go because we're losing a lot of access for our patients, but I think a lot of patients who maybe have been turning to, or solely have been using, these compounded versions will be pleasantly surprised if they do end up on a patented version. There are multiple stories out there of physicians saying they have [had] a patient coming in who is on a 1 mL [compounded] injection and transfer them to the 1 mL patented product and see crazy results after. Well, lo and behold, the original compounded version wasn't FDA-approved. Therefore, we can't confirm what the dosage was, but I think we can confirm, based on the results, that it was probably lower than the patented product, right?

I know it's unfortunate to hear that a lot of these medications are going to be unavailable, but switching over to the patented products actually may give you better results, especially for weight loss. So, it's not so sad, I guess, in a way.

Heath: Yeah. Neither one of us might have an answer to this, but I wonder -- when switching over to the patented products, we see people who are able to achieve more optimal results because they're on the FDA-approved patented product. How will that strengthen the evidence base such that insurers might be able to justify the ROI of covering these drugs for weight loss? I'm not sure, but that's what struck me when you were talking about that.

Kaylor: Yeah, absolutely. Just to hit it all home -- I know you and I have talked to people across the industry who say that compounded GLP-1s serve a purpose, right? Especially during shortages. We saw that here. But they're never meant to be a long-term sustainable solution, especially to the obesity epidemic that our nation's facing, right? I mean, it's estimated that over half of U.S. adults might qualify for a GLP-1. That's outstanding! That's like close to 130 million people.

But then again, if you think of that in a compounding concept or scenario, we can't expect our compounding facilities and outsourcing facilities to pick up the slack for 130 million people. That's crazy. Because then we're taking away from those individuals or children who are allergic to certain inactive ingredients in their antibiotics. It's a catch-22, right? Like, we need these compounding pharmacies, but only in certain circumstances. And they're definitely not a solution for these GLP-1s, and we've heard it over and over and over from many industry experts.

Heath: That's exactly what I was thinking when you said like, "compounding has its place," but I was filling in the end of that sentence with, "not at scale." It's not necessarily a solution at scale. I do think that it's important to start thinking about some of the more long-term solutions to this GLP-1 problem. Because like you mentioned, over half of U.S. adults might qualify for a GLP-1, which indicates a pretty massive chronic illness problem in the U.S. So, I was wondering if you could talk a little bit about policy solutions around affordability and not just around supply.

Kaylor: Yeah, and I think that all comes back to how we operate patents here in the US, unfortunately, and market exclusivity, right? I mean, GLP-1s are still under very tight patent protection. We only have two companies, and only one of those companies is based in America. So that means no generics, no biosimilars, no real competition of any kind to bring down the price, right?

And then on top of that, these companies are using patents to effectively block the competitors from entering the market for decades. And that does nothing for the patients. Take, for example, Ozempic's active ingredient, semaglutide. Their drug maker, Novo Nordisk -- there was a report that was put out. And according to that report, they had applied for over 300 patents on this one active ingredient in the U.S. alone. They were granted 154 of them.

The main compound's patents are now extended from 2026 to 2031. And then they added 49 more patents for small changes, like delivery devices, different dosages. The company has stretched its market exclusivity to, like, 2042. We're looking at no competitors until then. That's not okay for access at all. The only way to tackle the pricing is to tackle the extensive patent web that all of these large corporations have managed to capitalize on.

Heath: Mm-hmm. We can all recognize the way in which exclusivity might reward innovation, but it's also keeping prices high, like a miracle drug. I mean, there are so many other ways that GLP-1s are improving health outcomes beyond diabetes and weight loss, but just limiting it even to those two -- the way that it can improve outcomes for patients with some of the most expensive chronic illnesses. And yet we see that demand balloons at the same time that cost balloons, due to some of this market exclusivity, and it is really, really difficult to watch sometimes.

Kaylor: It's discouraging, and I can only understand being a patient, right? It's discouraging for me, and I'm not a patient. I don't take these drugs. So, I can only imagine.

Heath: Mm-hmm. Yeah, until we have this like more of a market with generics and biosimilars, we're going to continue to see these challenges, which, as you said, is super discouraging. Just knowing the positive impact that these medicines can have on people's lives.

I don't know if we should transition into talking a little bit about the oral GLP-1 drug. I know you reported a little bit on it, and I was able to do the copy edit on it, but I'll let you take it because you're the expert.

Kaylor: Yeah, well, guess I am happy to end this episode on a more optimistic note Although this is all speculative -- we don't really know at this point. But, at the beginning of the month of May, Novo Nordisk's oral version of semaglutide was accepted for review by the FDA. If that's approved, that'll be the very first oral GLP-1 for chronic weight management that is on par with the injections, which is huge, right?

We don't know the pricing yet, but I mean, we're looking at a 25 mg oral tablet for obesity that could come with some real advantages. There's no refrigeration needed, which the injectables do need -- easier to travel with. You can take it with you much easier than having to pack a cooler with your injections and stuff like that. And no needles. Anyone who is afraid of needles, I think they're cheering for this, right?

Heath: Love that.

Kaylor: Like I said, we don't have an estimate on price, and we don't know when this is going to be approved by the FDA, but I can imagine that this is going to be a game changer.

Heath: Mm-hmm. Yeah, I think so much about medication adherence, which is part of the overall debate about GLP-1s, mostly in terms of people being able to continue to pay for it. But beyond cost, barriers to medication adherence include whether the patient can tolerate taking the medicine. And that is a huge question for people who would have to be stuck with a needle regularly. It's not fun. I'm not in the position. I can't imagine that it's fun to do.

And I'm sure it's a lot easier in terms of the patient knowing how to take the med, right? Instead of, everyone knows how to -- I don't want to say everyone knows how to swallow a pill because that's also hard. As someone who coughed up her vitamin C earlier today, swallowing pills is hard. But, there's no training necessarily involved, whereas with the injectables -- you do need to make sure that you're following that correctly. But as you said, pricing remains a question, which will always influence access as well as payer coverage. Like you said, speculative, but hopefully promising.

Kaylor: Yeah, absolutely. And like I said, the main reason the shortage happened was due to the device. With the pill, the device is not even part of the equation, right? I can only imagine how much easier it'll be to get that medication into the mouths, if you will, of those who need it.

Heath: Mm-hmm. Yeah, absolutely. Wow, what a great way to end.

Kaylor: All right. Well, we have to wrap this up. I could talk about this all day long, Sara, but thank you so much for walking me through this today. And thank you for highlighting what this all means from the patient's perspective. I appreciate it.

Heath: Yeah, thanks. I feel like I learned something. I'm so glad that we were able to connect on this. Thanks for having me.

Kaylor: Absolutely. Thank you.