Episode 396: Buprenorphine, Fentanyl and the Opioid Crisis: What Medication for Opioid Use Disorder Really Does with Nick Casale, PharmD

0:00Nick Casale, PharmD: All right, everybody, I want to tell you about today's sponsor, Wired for Addiction. And honestly, I am so excited about this partnership. You might remember Dr. Evelyn Higgins from when she came on the show to talk about the biomarkers of addiction. That episode landed in such a powerful way for so many of you. And I really believe in the work she's doing. Here's the thing. If you or someone you love has been caught in chronic relapse, addiction switching, or treatment that only works for a while, the issue may not be behavioral. It may be biological, and that changes everything. Dr. Higgins and her team actually measure the underlying biomarkers driving these patterns, dopamine, cortisol, inflammation, mitochondrial function, and then build a personalized plan to bring your biology back into balance.

0:52Nick Casale, PharmD: She put together a free guide for you, the Biology of Addiction 10 Core Biomarkers. Download it at theaddictedmind.com forward slash wired. That's theaddictedmind.com forward slash wired. There'll also be a link in the show notes. And I want you to know, you are not broken. Sometimes your biology just needs to be understood. And I think that brings a lot of hope. All right, on to this episode. All right, everyone. Welcome back to the Addicted Mind podcast. I'm Dwayne Osterlin, and I am so glad you're here.

1:31Duane Osterlind: And the plans at the time were all over the board on how they were going to pay for someone to get treated for opioid use disorder. And there was no unified approach. Some of the plans said, we'll pay for this for six months, and then you have to come off of it. Some plans would say, we'll pay for it, but we want you to get your own drug screened every month. And if you fail, you're in drug screen, we're kicking you off treatment.

1:58Nick Casale, PharmD: Now, if you've loved somebody caught in opioid addiction or you've been there yourself, you know how frightening and lonely it can feel. And now that fentanyl is in almost everything on the street, the stakes are higher than ever. My guest today is Nick Casale. Nick is a pharmacist who spent the last 15 years working in opioid use disorder. He started inside the Medicaid health plan just as the opioid crisis was exploding. And today he's the senior director of medical affairs at a pharmaceutical company that develops treatment for opioid use disorder. And he's seen this crisis from the insurance side, the treatment side, and inside jails and prisons.

2:42Nick Casale, PharmD: And in this episode, we talk about what buprenorphine is and how it works in the brain, why synthetic opioids are making recovery so much harder, and what the real world data shows about long acting monthly injectables. And we also get into the misuse and the diversion and the stigma that keeps four out of five people from getting medication at all. So before we jump in, if this podcast has been meaningful to you, please take a moment to rate The Addicted Mind on Apple Podcasts or Spotify. Even better, write a review. Those reviews help people who are struggling find this show and follow us on social media so you stay connected.

3:25Nick Casale, PharmD: All right, everyone, let's jump into this episode.

3:35Nick Casale, PharmD: All right, everyone, welcome to the Addicted Mind. I have Nick Casale with me, and we've got a really important topic to talk about. But first, Nick, introduce yourself.

3:47Duane Osterlind: Thanks, Dwayne. Thanks for having me. My name is Nick Casale. I am a pharmacist by background. I've been working in the field of addiction medicine for the past 15 years, specifically with an opioid use disorder, which I know we're going to talk a little bit about today. Currently, I work for a pharmaceutical company within their medical affairs division. So my team is responsible for having scientific discussions with healthcare professionals, so doctors, nurse practitioners, and physician's assistants. We also field medical inquiries that come into our department, so more complex questions or cases related to treatment.

4:32Duane Osterlind: And then we also talk with key opinion leaders in the area of addiction medicine. So talking through the research that they are doing, some of the research that we're doing, and just have that back and forth scientific dialogue. So that's what I'm doing right now and happy to be here today.

4:50Nick Casale, PharmD: It's great to have you. I'm excited to get into the wealth of knowledge and the data about all of this. But first, just what brought you to this specific field, this specific part of treatment? How did you start working in the addiction field?

5:08Duane Osterlind: Yeah, so a very windy journey to get to where I was. But after I became a pharmacist, like most pharmacists fresh out of school, I went into retail pharmacy. That was not really a passion area of mine. So I quickly started looking for other opportunities. And I had a friend at the time that was working with health insurance companies as a pharmacist. And they were looking to bring someone on to help look after formulary design. So what medications are covered by insurance companies or if there's prior authorizations, things like that required. So someone more clinical and background. So I joined an insurance company in the state of Pennsylvania that was focused on Medicaid at the time.

5:58Duane Osterlind: So that was our patient population was Pennsylvania Medicaid. We also had a couple other states as well. And when I joined the organization as a clinical pharmacist, my areas of focus that I was assigned at the time were opioids. And this is back in the early 2010s. So this is really when the opioid crisis was blowing up and we were starting to see it at the plan level that there was a lot of overutilization of opioids that the plans were paying for. And around that time, CMS, which is the Center for Medicare and Medicaid Services, put out a kind of directive to the plans that we had to get some of the opioid use under control, that there was a lot of overutilization.

6:47Duane Osterlind: so I took over that program for the plan and I always say this that once you start to dabble in the opioid overutilization you somehow find your way into the flip side of it which is now you have patients that have opioid use disorder so I was on the looking after the addiction medicine part of the benefit as well and at the time transmucosal buprenorphine which is one of the medications that we'll talk through that treats this space was our number two drug spend at the plan behind Abilify, which is a drug for schizophrenia and some other disorders. So the plan was paying a lot of money, not just in opioids as a class, but in the treatment options.

7:32Duane Osterlind: So through that, I really got to know one of the manufacturers of the medications to treat opioid use disorder. And at the time, I was trying to work with the other plans in the state to come up with standardized treatment options in this area. So at the time in 2010 or so, people were looking at the space in a very stigmatized way, which is still occurring today, but we've made some progress. And the plans at the time were all over the board on how they were going to pay for someone to get treated for opioid use disorder. And there was no unified approach. Some of the plans said, we'll pay for this for six months, and then you have to come off of it.

8:17Duane Osterlind: Some plans would say, we'll pay for it, but we want you to get urine drug screened every month. And if you fail a urine drug screen, we're kicking you off treatment. So we came together.

8:27Nick Casale, PharmD: It probably isn't very good when you're looking at addiction.

8:29Duane Osterlind: No, 100 % not. We've learned a lot in the way, but not a good approach. So I was working with the other plan to try to come up with a unified strategy on this. And, you know, after we got through that process, the manufacturer, they approached me and said, would you like to come on and help talk to other Medicaid's across the country? Because we're actually facing similar situations and every state is different. So that kind of brought me over to the industry side. And my initial role was to talk to Medicaid directors that were mostly pharmacists. and talk through what they were seeing in their states and Medicaid populations for opioid use disorder and how they were approaching the treatment.

9:12Duane Osterlind: And just like Pennsylvania, it was all over the board. So we were just walking through the benefits of treatment, some of the outcomes that we were seeing.

9:20Nick Casale, PharmD: So there was no universal way to treat this. No. People hadn't, I guess, hadn't come up with a protocol to standardize care or bring about the most effective care. It was kind of all over the place when you're looking at this substance use. That's right. disorder.

9:34Duane Osterlind: That's right. That's right. Now, the drug at the time obviously had a unified way of prescribing the medication. But from a payer standpoint, from Medicare, Medicaid, commercial insurers, there was no real unified way on how to, one, approve these medications for treatment and how long to keep people on the therapies. So it was all over the board. And really from there, I've stayed with the company for a long time because I've just fell in love with the space and have kind of moved on from... I still assist in the payer space, but my focus has shifted over the years to build out a team of medical professionals that have experience in this area that go speak to what I mentioned in my intro, talk to the key opinion leaders in addiction, and kind of relay that information out.

10:28Duane Osterlind: So my team's really a conduit of medical information and scientific exchange. And that's what we do now. And along the way, different treatments have come out. So it's not just a transmucosal or oral therapy that you have to take every day now. There was the introduction of...

10:45Nick Casale, PharmD: Tell me for people out there that don't know what that is. Sure. Transmucosal. What does that mean?

10:51Duane Osterlind: Transmucosal. So the main drug that is being used in treatment right now for opioid use disorder is a molecule known as buprenorphine. Buprenorphine has a long history in and of itself in the US. And also the way that it's been regulated over the years has also been very unique in this space. But buprenorphine needs to be taken under the tongue. So it's not something you can swallow. Just due to the nature of the compound, if you were to swallow buprenorphine, It has a really poor absorption in the gut and it just doesn't work. So you have to deliver it transmucosally, meaning the drug gets absorbed under the tongue.

11:32Duane Osterlind: It bypasses that gut metabolism and starts working immediately in the brain. So that's how the drug was initially launched in the US was in a tablet form that was placed under the tongue. It evolved into a film formulation. So something that was like in a strip form, kind of like a Listerine strip, if you want to make a comparison. And then that treatment has evolved over the years to then introduce a long-acting injectable, which now there are a few on the market in both weekly and monthly formulations. And that's kind of the newest modality in the space. So buprenorphine is the major player in opioid use disorder for medically or medication-assisted treatment.

12:17Duane Osterlind: There's other products in this space too that you can use to treat opioid use disorders such as methadone, which has been around for years and years, and also naltrexone, which is another option that's an injection, but by and large.

12:31Nick Casale, PharmD: Let's talk a little bit about buprenorphine, what it is for people out here who are listening and maybe they're hearing this for the first time or they have a loved one who's maybe getting into treatment and they don't even know what this is. Can you give us a basic description of that so that we know? And then we'll go from there. I also want to dig into, you know, we were talking earlier before we were recording that you had a lot of stats and data. So I want to get to that too. But just lay a baseline here of what this is and what's going on.

13:04Duane Osterlind: Sure. So buprenorphine is a partial opioid agonist. So that's a fancy term, meaning that it as a molecule binds to the same receptors in the brain as an opioid would. So whether someone is using just prescription opioids or something like heroin or fentanyl, they all bind to the same mu opioid receptor in the brain. So buprenorphine binds to that same exact receptor. However, unlike other opioids, that when it sits on the receptor and really lets all of the chemicals release at the receptor site, which causes that euphoric feeling and really drives the addictive behavior, buprenorphine only partially opens that molecule.

13:57Duane Osterlind: So it's helping to keep people out of opioid withdrawal. And because that buprenorphine is attached at the site and the brain, it's blocking other opioids from being able to attach to the site. Because two really good things about the buprenorphine molecule. One, it does a really good job of finding the site in the brain that it has to work on. So just the way chemicals work and drugs work in general, everything has a different affinity or how well it attaches to the site. Buprenorphine outcompetes every other opioid for the same site when it's in a mix or a race to get to the site. So that's number one.

14:42Duane Osterlind: Number two, molecules, when they attach to a site, they have something called how long they bind for. So buprenorphine binds for a really long time. It doesn't drop off. Whereas other opioids, such as say, let's talk through like heroin. Heroin is a bouncy compound. It attaches and then falls off and then looks for another one to attach to and falls off. It's constantly doing this kind of musical chairs. Whereas buprenorphine sits on the chair and doesn't move. So those are really two important things about buprenorphine. And once it's sitting on that chair, no other opioid can come in and grab its spot, right?

15:22Duane Osterlind: So it's helping to keep patients out of opioid withdrawal. It's also helping to potentially reduce craving for opioids. And also, because it's not providing that full force effect of an opioid, it's not allowing a patient to necessarily go into an overdose situation, unless they're using some things on top. But it's helping with that too. So it's overall just doing its job in the system. And the reason we need medication-assisted therapy, such as buprenorphine, is if someone just goes cold turkey, like abstinent from opioids, their brains are so used to having opioids stimulating the receptor site that if you don't have that you go into extreme withdrawal and it's very painful and causes all sorts of side effects which is why especially patients that are addicted to fentanyl or you know all these newer semi-synthetic or synthetic compounds these withdrawals are horrific they're really bad experiences for the patient to go into and they can even be life-threatening right

16:30Nick Casale, PharmD: Right. So this binds to the receptors. It gets there first. It likes to be there and it holds that space. Like you were talking about tolerance, we can generate a tolerance to these drugs. So we need more and more. Our brain needs more and more because we don't make it ourselves anymore in a way. So this is a buffer for that. It's also an opioid itself, but it acts a little bit differently. Would that be correct? That's correct. So now we have this compound that helps with that. Let's talk a little bit about the stats that you were talking about, like looking at the treatment because it sounds like for you, you've had the experience.

17:10Nick Casale, PharmD: You've seen that the overprescription, the overfilling of opioids and to the opioid crisis all the way to this other side of trying to work with people through that crisis. So let's jump in and talk Talk about like what you're seeing and especially around how these drugs work into treatment and how are they showing up and how, what is the evidence that shows their use is important and valuable to this to recover?

17:40Duane Osterlind: So just some stats with opioid use disorder in general. And this first one's a little bit older, just due to the nature of these reports, how they come out. But there's roughly 4.8 million adults that have opioid use disorder in the United States. So just think about that number for a second. But out of that, only one in five are being treated with a medication to help with opioid use disorder. So huge population that has the disease, very small amount that are being treated. And right now in the US, there's roughly 45 ,000 opioid overdose deaths per year. And most of them now are with synthetic opioids.

18:31Duane Osterlind: Oh, I know. It's the equivalent of a Boeing 737 crashing every single day is the amount of people that are dying each day from an opioid overdose. And a lot of them are not being treated. So the landscape has also evolved in opioids and opioid use disorder in general. So back in the 1990s, it was prescription opioids that were driving this initial surge in overdose-related deaths. And everyone's heard of it, right, from the Purdue days with the Oxycontin and overprescribing. This started that first wave of overdoses. The second wave really came around 2010. And we were just talking about that when I was joining the plan.

19:19Duane Osterlind: And we were really cracking down on prescription opioids. And what happened was patients had a limited access now to opioids, and they moved to heroin, which was easily accessible on the street. It was very cheap. It was cheaper than buying prescription opioids cash from a pharmacy. And that increased the overdose deaths because heroin was just more potent. And it's coming from a drug supply that you don't necessarily know what's in it. The third wave of this space came in 2013. This is when we really saw the introduction of synthetic and semi-synthetic opioids coming into the drug supply. So something that everyone's really hearing of now, like fentanyl, right?

20:04Duane Osterlind: And I can confidently say in the US, there is no more heroin left in this country. It all has fentanyl in it. Even if you think you were buying heroin, you're most likely getting something that has fentanyl. or things like carfentanil or even more potent synthetic opioids that are causing these overdose deaths to increase because they're so potent. So that's what's happening in this space. And a lot of these now illicitly manufactured synthetic and semi-synthetic opioids are coming from China and Mexico and being just put into the drug supply, along with other things that are just naturally occurring.

20:44Duane Osterlind: And it's driving these opioid deaths. What it's also doing is it's making this disease much harder to treat. Because now instead of naturally occurring opioids that are in prescription products, now you're dealing with synthetic and semi-synthetic that are way more potent. And because of that, they're upregulating all the receptors in the brain. And then when you try to treat the space, it's harder to treat.

21:09Nick Casale, PharmD: When you say upregulating, what do you mean by that? What's happening with these synthetics?

21:13Duane Osterlind: So what's happening is everyone has a baseline amount of new opioid receptors in their brain that opioids can naturally attach to. As you take opioids and things like even fentanyl that are very potent, your body likes the response that the opioid's given. So what does it do? It creates more of those receptor sites in the brain. So now that more opioids can attach to the site. On the flip side of that, when there's no opioid attached because all drugs eventually do leave the system, now you have way more unoccupied receptors that need stimulation, which is now causing these extreme withdrawals or the need to find more or use even stronger opioids to help maintain the amount of receptors on the site.

22:00Duane Osterlind: So that's what's occurring.

22:01Nick Casale, PharmD: So it's physically changing your brain. You're developing more of these opioid receptors so that when you get off, now your body in no natural way can fulfill that.

22:14Duane Osterlind: That's right. And that's why medications are so important to treat this space.

22:18Nick Casale, PharmD: So let's talk about some of the data you're finding out about these medications. And especially, I want to talk about the long-lasting injectable. And I know that's newer for this medication and its evolution. But I think some of these medications, when we look at this from a biological perspective, in a way, may be a necessity as part of treatment. There's something that has to be part of the picture. Yes.

22:46Duane Osterlind: Yes. So buprenorphine now has been around for quite some time, and there's very strong evidence and consensus that the drug works for helping to treat patients with opioid use disorder, enter into a state of remission or recovery, and regain control of their lives and to really get their life back. It's very well documented now. The treatment duration has always been something that's been a point of controversy. And I let you know, like back when I was with the insurance companies, there were some that had limitations on how long someone could be treated with puberenorphine. Luckily, that is now mostly a thing of the past because the insurance companies now recognize that the longer they keep someone on a therapy, that they do enter into a state of remission or recovery.

23:39Duane Osterlind: And guess what? happens, they end up not going into the ER. They end up not being really expensive patients. Or if they're injecting illicit drugs, maybe they come in contact with a dirty needle that then causes hepatitis or endocarditis or these really expensive things to treat. So a lot of the payers in the space now have dropped these limitations on treatment. ASAM, which is the American Academy of Addiction Medicine, American Society of Addiction Medicine, I'm sorry, they have come out and said that you need at least three months of treatment to have benefit, but longer durations are associated with more positive outcomes, right?

24:21Duane Osterlind: So I think we're all now on the same train that the longer you're treating a patient, the more time they have to enter into the state of remission or recovery. And really, there should be no duration on these treatments. It should be a a decision that's made between the patient and their treating provider. And not saying these have to be lifetime therapies, but if that helps patients recover and regain control of their lives, then just like with a blood pressure medication or a diabetes medication or anything like that, you don't have to come off of these things. I think blood pressure is a good example, right?

24:58Duane Osterlind: If you have high blood pressure and you take medications, but then maybe you lose 50 pounds and you start working out and you start eating better, maybe you don't have high blood pressure anymore and you can come off the medication. Well, same thing with opioid use disorder.

25:12Nick Casale, PharmD: Once you get to that sorted space, you can make that decision with your doctor.

25:16Duane Osterlind: That's right.

25:17Nick Casale, PharmD: Of what works best for you. And a lot of times once somebody's life is more stabilized and they have structure in their life and they have support in their life and they're in a good place of recovery and living well, then yeah that might be a real possibility to be able to do that and find that path whatever that works but i i think having the freedom to do that i think is so important and it's it you know these medications i feel are are so incredibly valuable to people who are really struggling and especially now as you're talking about the synthetic opioids and the impact on the brain that these are having that these may, they have to be a standard part of care, I would imagine.

26:02Duane Osterlind: That's correct. And this is kind of where the long-acting has really come into play. Because with these high-potency synthetic opioids that are now the main cause of opioid overdoses in the country, there's expert consensus now that we need higher plasma. And plasma is a fancy word for like how much buprenorphine is in the brain. exposure at continuous levels to really help with the opioid withdrawal that we're seeing and the impact that the high-potency synthetic opioids are having. So with the injections that are out on the market now that are a relatively newer treatment modality, they provide this continuous exposure to buprenorphine, whereas with the transmucosal or oral therapies that have been around now for quite some time, they require daily dosing.

26:58Duane Osterlind: And some providers even dose them more than once a day. Because what happens with any sort of oral therapy is you take it and your body's instantaneously trying to remove the drug from your system, you know, through the liver, you know, and eliminating in your urine. With the injections, you get the injection and say for the month long injections, you receive the one injection, you're immediately exposed to buprenorphine. And now just due to the nature of how these injections work, it's providing a continuous release of buprenorphine that's able to keep all the mu opioid receptors in your brain stimulated.

27:37Duane Osterlind: And it's allowing the buprenorphine to block the receptor sites. So say you do use an opioid on top, if you relapse or if something happens and you happen to use an opioid, there's no place for the opioid to go because the receptor sites are being blocked by this buprenorphine. And now you don't have to have that daily reminder of, did I take my medication or even do I want to take my medication today or this weekend if you're planning on using an opioid?

28:08Nick Casale, PharmD: I would imagine you have a higher compliance. You get through that. I mean, it's hard for any of us to do something every single day and it can be really, really challenging. And so it sounds like that really gives people some structure and hope that they can get some time, right? I mean, it's time. They can get some time. Their brain can repair. They can start getting things in their life sorted out. I think that sounds incredibly, incredibly helpful to them. What does the data show when we look at this? What is the data showing us with success for treatment on this and recidivism rates and all of that.

28:51Nick Casale, PharmD: Do you have that data as well?

28:53Duane Osterlind: Sure. So with the injections that are on the market, when they were undergoing their clinical trials with the FDA and for all the FDA submissions, the FDA's main endpoint that they wanted the manufacturers to look for was opioid abstinence. So meaning that the patients are not testing positive for opioids in their urine. And they're self-reporting to the investigators that they have not tried to misuse an opioid over the past week. So that was the endpoints. The drugs that are on the market today that are in this long-acting space, they all met the endpoints that the FDA wanted for abstinence.

29:37Duane Osterlind: So that's why primarily all of these medications have been approved over the past few years is that they were able to provide more abstinence from using opioids versus having no treatment at all. And they were safe. So, you know, in clinical trials, there's a huge emphasis on drug safety and looking at adverse events that occur when you're taking a medication. and they were able to clear those two hurdles for efficacy and safety to be able to then be on the market in the United States. So abstinence, though, yes, it's an FDA-driven endpoint that they wanted the manufacturers to show. But to your point, it's not the only endpoint that we really need to look at for opioid use disorder because there's going to be times in this space where patients relapse.

30:29Duane Osterlind: And it's inevitable, right? It's just part of the treatment journey and patients shouldn't be penalized because of it. So the more important things in this space are the things that are beyond the endpoints of the trial. So things like you were mentioning, recidivism, right? And this is especially important in the criminal justice setting where there's a huge population of patients that are within our carceral system in the United States that have opioid use disorder. Up until maybe very recently, there was no treatment in jails or prisons for opioid use disorder. This is only a very recent change that's occurred in the carceral space to start treating opioid use disorder.

31:13Duane Osterlind: And a long-acting injection is a great option for this sort of setting because as patients get released from small jail stints or are being released back into the community, the first thing that a lot of patients do, especially if they're not being treated in the jail, is go find an opioid to use. And because now they've maybe lost tolerance, it's a high-risk time for an overdose. So by giving an injection on the way out of the facility, it allows patients, one, time to go find a provider to continue their treatment journey. And two, because the injections in their system say they do end up using an opioid.

31:59Duane Osterlind: Like I mentioned before, the mu receptors are blocked now in the brain. So it's almost like a protective effect against a potential overdose or having the desire to use an opioid in general. So, you know, these are really strong points for recidivism. I do a lot of work in the carceral setting, you know, talking to sheriffs and medical directors in jails and prisons on why it's so important, not only to treat in this system, but the importance of having medication on board when patients are being released from jails or prisons so they don't come back into the same facility.

32:39Nick Casale, PharmD: Let me ask you this. As you're talking to these individuals and you're talking to, you know, these providers or, you know, like you said, the sheriff's department in these prisons, What is some of the pushback that you've got to overcome or maybe some of the stigmas or misunderstandings about addiction that come up that you kind of see over and over again that you have to help someone see their way around?

33:05Duane Osterlind: Yeah, I mean, highly stigmatized, like you just said, especially in the jails and prisons. And from the sheriff's perspectives or the warden's perspectives, over the years, buprenorphine has been one of those things that unfortunately has been one of the top divertable medications in jails and prisons. And it's not necessarily all for the wrong reasons. It's there was no treatment available in jails and prisons. So if a patient could get their hand on buprenorphine when they were in the jail and prison, they weren't necessarily using it to get high. They were using it to suppress the precipitated withdrawal or the withdrawal symptoms that they were having within the jail that was not being treated, right?

33:47Duane Osterlind: So from their perspective, they were viewing it as a divertible medication. It was causing a lot of security issues in the jails and prisons. So just over the years, they've kind of just had a bad feeling about it from a security and diversion perspective and not really looking at the evidence behind treating the disease. Now, like I've mentioned, over the past few years, the tides shifted. And now most jails and prisons, not all, but a way bigger majority than a few years ago are offering treatment in jails and prisons for opioid use disorder. And now what we're trying to convey with the long-acting injections is one of the main issues in jails and prisons is staffing.

34:33Duane Osterlind: There's not enough staffing in jails and prisons, and especially on the medical front, to have to bring a patient from their cell to the everyday. One, it requires a lot of security personnel. It requires staff to administer the medication. It requires observed dosing to make sure that the medication wasn't cheeked or is being diverted back into the jail. With the injection, they just have to bring them once a month, potentially, for an injection. So from a staffing cost, and there's been evidence published on this, that NCCHC, which is the National Commission on Correctional Health Care, has put out there that long-acting injections actually do save on staffing costs within the jails and prisons.

35:18Duane Osterlind: So yes, the medication cost is higher up front because these are newer treatment modalities. They're branded therapies. They're not generic yet. So there is a bigger upfront cost, but you're seeing a lot of downstream effects. And now because that injection's in the system, the patients too aren't being harassed when they're back in their prison block or jail cell on having the medication be diverted or cheaped to divert out. So the security issues are less.

35:48Nick Casale, PharmD: So how can buprenorphine be abused and that part of it? I think that's also important to be able to understand some of the downsides of this.

35:57Duane Osterlind: Correct. And so buprenorphine is abusable. And let's talk about that for a second. So with the transmucosal products, when those initially launched in the US, they were buprenorphine-only tablets that went under the tongue. Now, like I mentioned before, if you swallow that tablet, it does nothing. If you put it under the tongue, it starts eliciting a response. Now, if you inject it, if you kind of get it into a solution and inject it, now you're getting an even more intense response. And for those that don't necessarily have the tolerance for opioids, it is activating the mu site. So, you know, someone potentially has the risk of getting someone high.

36:43Duane Osterlind: Now, if someone is not opioid naive and they're used to opioids, And buprenorphine will not necessarily be the first choice medication that someone would want to take if you offered, say, buprenorphine and fentanyl side by side, if your intention is to get high. Right. But that being said, it has been a divertible product to the point where after the initial product launched in the U.S., the FDA asked the manufacturer to go back and put naloxone in the product. So in some tablet and the film forms of buprenorphine that are out there, it's a combination of buprenorphine and naloxone. And the only reason the naloxone's in there is if the patient were to inject it.

37:24Duane Osterlind: Because if it's injected, the naloxone now outcompetes the buprenorphine for that receptor site and is not allowing the buprenorphine to bind. So it's almost like a kind of a way that the FDA asked the manufacturer to put this other drug in to reduce down the divertible effects of the drug. Whereas if naloxone, if the drug's taken how it's designed under the tongue, then naloxone isn't absorbed and does nothing, right? Not only that buprenorphine is working for its intended use, but the injection just has buprenorphine in it just because there's no real, there's no divertible risk there with the injections, how the FDA has approved them, they are required to be shipped to the provider's office where they're being injected so that the patients never actually end up touching the syringe or the injection.

38:17Duane Osterlind: So there's more, you know, safety around those sorts of the injectable forms. Yeah.

38:23Nick Casale, PharmD: What is some of the, you know, as you're seeing this take place, what's some of the the benefits that you're starting to see in the data. And also, I guess I want to see that, but also, I mean, medication is part of the picture here, but it's, I really don't think it's the whole picture. Like we were kind of talking a little bit earlier that this has to be combined with treatment and therapy and all of that.

38:50Duane Osterlind: Yes, exactly. All of the above. I mean, I've always said this since I've been working on buprenorphine, that buprenorphine is a great molecule, but without all of those support systems that you just mentioned surrounding the patient, it's just not going to be a miracle cure, right? So you need things like counseling. You need things like the support structure in place, any sort of behavioral intervention, anything that's just helping move the patient in the treatment journey. It's not just the medication. So whether you're on the tablet, the film, or the injection, any of them, the way they work is they will work exponentially better if they are surrounded by all those various support options like you just mentioned.

39:37Duane Osterlind: So that's with the treatment thing. On the research front, now that these medications have been on the market for quite some time, tablet, film, and injection, as a manufacturer, we're doing a lot of research in this space, which we call real-world evidence. So real-world evidence is something that is not looking at the drug in a controlled environment. The controlled environments are great to get drugs on the market, So to prove that they work better than placebo, to meet safety and efficacy endpoints. But what controlled trials don't really show us is forget the controlled situation. That's, you know, patients are going into a site and talking to an investigator and getting paid and all this sort of stuff.

40:25Duane Osterlind: Now the drug's in the real world because it's approved. What's happening with the drug now that it's commercialized and in the space? So that's really the area that we focus on now as a company is, hey, what's happening out there with the medication, whether it's the transmucosal, the film, or the injection, what's happening in the space of medication-assisted therapies or these medications for opioid use disorder. So we're interested in things like overdose. So for patients that are being treated, are we seeing a reduction in non-fatal overdoses? And the answer to that one is yes. Patients that are being treated with transmucosal or long-acting injections, we're seeing less and less non-fatal overdoses.

41:13Duane Osterlind: So those are the overdoses that patients are being rescued from with naloxone or a reversal agent, and then being brought into an emergency room and surviving the overdose. So we're seeing good effect there. We're seeing good effect on things like infectious disease, which I mentioned before. So does treating in this space reduce the risk of things like bacteremia or endocarditis, osteomyelitis, these things that cost hundreds of thousands of dollars potentially to treat in an inpatient and outpatient setting that are unrelated to the buprenorphine, but are a consequence of opioid use disorder.

41:56Duane Osterlind: So looking at things like that, we're looking at patients' treatment journeys. So how are patients responding with regards to their patient-reported outcomes? So are patients reporting to us that they're able to enter into a state of recovery or remission? Are they able to get a job, go on commercial insurance, stay out of the carceral system? We're looking at all sorts of things like that. So there's a lot of great data that's coming out there that's unrelated necessarily to the drug safety and efficacy because we know the drug works and we know that it's safe. So we can put those two things on the shelf.

42:34Duane Osterlind: That doesn't necessarily matter as much anymore. Let's look at all the other outcomes that we're seeing with treating patients in this population. And remember what I said in the beginning, only one in five patients is being treated with anything. So there's a long way to go in this whole space.

42:50Nick Casale, PharmD: Right. And I think this This brings up the question of how do you give access to people who need it, who may not be able to afford these drugs? You know, there's the cost and all of that. But looking at, you know, from a society perspective of getting these helpful medications to everybody. I mean, that's its own challenge. How we view it as a society and how we treat people who are struggling with this, right? Right. There's a whole I mean, we could have a whole conversation about that.

43:21Duane Osterlind: Yes. And we've made great strides and not just our company, but the other companies that are in this space on working on access related issues. So, you know, I'm really happy to say that for both the tablets, film, and injections, the access now is the best that it's ever been with very limited hurdles, like there used to be, to get treatment in this space. So if you have any form of insurance, whether that's Medicaid or commercial insurance, I can pretty much guarantee you that if you have an opioid use disorder and you're willing to enter into something like a medication-assisted therapy, there will be something that's covered for you to help you at a very little to no cost.

44:13Duane Osterlind: The payers are behind it now, the insurance companies, they see the value in treatment, the evidence is out there on how this works. Now, there's always patients that fall into that third bucket of uninsured. So there are options out there for patient assistance, and there's a lot of great generic options in this class now on the transmucosal side, whether that's the tablet or the film side. there's you know generic manufacturers that make the drug for relatively inexpensive so if you are having to pay cash it's not as bad as it used to be because these products aren't all just branded anymore right but it's making the hurdle to actually go get treated so you know just going back to that stat you know that one and five are being treated with this well what if three and five were being treated and how come there's still this big delta of patients that aren't being treated with anything.

45:12Duane Osterlind: That's where we have to try to move the needle now.

45:15Nick Casale, PharmD: Well, I think that's a lot of that. Look at the shame around addiction, how we view addiction and some of the whole history of how we've treated anybody who's struggled with addiction and breaking that stigma so people can reach out and get support and get help. And it's good to know that there are options out there that, you know, I think a lot of people out there want to help and to get that help. So we're coming up on our time, Nick, I appreciate you coming on and sharing all of this information, all this data, so people can understand what's going on, understand what options they have. Before we go, I always like to ask every guest one question, and maybe someone out there is struggling with opioid dependence or they know somebody who's struggling with opioid dependence and you could tell them one thing, what would you want them to know?

46:10Duane Osterlind: I would encourage them to seek out some sort of treatment with these medications that are known to be safe and effective. The providers out there that treat this particular space are compassionate. They will talk to you like a human now. The stigma has really decreased on the treatment side of this disease. And I think by just recognizing that it is a disease, it's chronic in nature, but things like medications can help get someone back on the right path to really reclaim their life, that's the number one thing I want to get across is just be brave, seek out the treatment. And once you go on the treatment, just see how much it can change your life and get you back into that state of where you used to be or where you want your life to become.

47:12Duane Osterlind: And these medications are a great option to help in that treatment journey. It's not the only thing like we mentioned. There's a lot of other things around it, but it's something that will really help patients on their treatment journey and encourage you to look out there online and to see other patients' testimonials on their experience with the buprenorphine-related drugs in this class and just to see the effects that they've had. And there's a lot of success stories out there. And I always advocate for peer mentorship in this space as well. And there's a lot of peer advocates that work or are working in the HCP offices that treat the space now.

47:54Duane Osterlind: And they will help guide you along that journey because they've been there themselves. So just make that first step. And I guarantee that you'll be happy with your choice.

48:05Nick Casale, PharmD: Reach out. Just keep reaching out. Nick, if somebody has questions or they want to get a hold of you, how do they find you?

48:12Duane Osterlind: So, I mean, you can find me. I'm on LinkedIn. So feel free to reach out on LinkedIn. Just Nick Casale. And you can message me through there, connect through there. And yeah, be more than happy to respond or answer anything that I can.

48:27Nick Casale, PharmD: Great. I'll put that link in the show notes to that so they can find you if they have any questions. Nick, I just want to thank you for your time coming on, doing this work and putting all that wisdom out there. Thank you so much. Thanks for having me.

48:43Nick Casale, PharmD: I really appreciate Nick coming on the podcast. One thing that he said that really sticks with me, and I see this in all the work that I do, that relapse is part of the treatment journey and people shouldn't be punished for it. For so long, we've treated addiction like a moral failure. We've kicked people out of care for a positive drug screen and cut treatment off after six months. The science points the other way. People need time for the brain to heal and time to rebuild a life. Medication can help create that time. And it works best alongside counseling, support, and people who've walked this road themselves.

49:23Nick Casale, PharmD: You don't have to do this alone. If you'd like to connect with Nick, you can find him on LinkedIn. I'll have all the links in the show notes at theaddictedmind.com. So check them out there. And if this episode gave you a little bit of hope, do me a favor, rate and review The Addicted Mind wherever you're listening. Write a review if you can. Share this episode with someone who needs to hear it. And follow us on all social media. Every review and every share helps someone who's stuck in the dark find a conversation that could be the start of something different. So thanks for being here. And I'll talk to you on the next episode.

50:10Thank you.