December 5, 2024
Welcome to Perspectives, Leerink Partner’s signature podcast, where we share our insights and interview leaders across the industry to get their perspective on how they’re driving innovation. We’ll also be digging into the backstory to learn more about what has most influenced their success. Be sure to check out all episodes by Leerink Partners.
Mel Whittington: Hi, everyone. I’m Mel Whittington. I’m a managing director and Head of the Leerink Center for Pharmacoeconomics, which is a division of MEDACorp, an affiliate of Leerink Partners. The Leerink Center for Pharmacoeconomics was launched to evaluate and communicate the societal impact of healthcare innovations. Earlier this month, we released our first CPE exclusive, which was our first evaluation that explored the societal impact of Cobenfy, a recently approved treatment for adults living with schizophrenia. There’s excitement around this product because evidence suggests it can reduce schizophrenia symptoms similar to commonly used second-generation antipsychotics, but with fewer side effects. And these side effects can be quite troublesome. The side effect we focused on our report was weight gain, as weight gains frequently reported in other commonly used antipsychotics and seems to not occur with Cobenfy. In our report, even under conservative assumptions, assuming that the only differential treatment impact between Cobenfy and other second-generation antipsychotics was weight gain. Our analysis suggested that Cobenfy could actually be cost saving to society if you consider the cost savings from less diabetes, less cardiovascular disease, which are downstream complications of weight gain, and then also that these, this results in improved quality of life and longer length of life, which has an important impact on patient productivity among many other outcomes as well. So, in our report, we saw even a list price of around 22,000 dollars per year our analysis suggested that Cobenfy’s societal benefit is greater than its price. And so, in this case, it seems like society is getting a bargain. The intent of our CPE Exclusive was to extrapolate and synthesize available evidence to help the industry and public better understand what this innovation might mean for patients, caregivers, the health system, and just society as a whole. At the Leerink Center for Pharmacoeconomics, we don’t only want to evaluate the societal impacts of innovation. We want to communicate them. We want to be the storytellers of innovation. We want to hear from people with lived experiences, whether that’s a patient, a patient advocate, caregiver, an innovator, or an investor. We want to hear their stories. And so today it’s my pleasure to be joined by Holly Krasa. Holly is a neurobiologist who wears many hats and can speak to many aspects of innovation from product development to product approval, to product access. She’s also uniquely positioned to provide perspective on a variety of different stakeholder groups within the healthcare industry as it relates to schizophrenia. I’ve had the pleasure of having a lot of conversations with Holly and each time I leave empowered and full of new information, and so I am honored she was willing to be a guest in our podcast today. Holly is a board member of the Schizophrenia and Psychosis Action Alliance, which is a patient advocacy group leading the charge to advocate for people living with schizophrenia and psychosis disorders. In this role, she works closely with people living with schizophrenia and caregivers, and so she can speak to the impact schizophrenia has on their daily lives. She was also the head of health outcomes at Otsuka, where her work focused on evidence generation to support regulatory filings. policy, and reimbursement, and so she can also speak to the approval and access landscape for schizophrenia. And now she’s the CEO and Managing Director of the Blue Persimmon Group, which is a nonprofit advocacy group and life sciences consulting firm. Holly, thank you for joining this podcast.
Holly Krasa: Thank you so much for that kind instruction. It’s an honor to be here for such an important topic.
Mel Whittington: Thank you. So just starting out, can you tell me a little bit about how you enter the field of neurobiology for one and then eventually became the head of health outcomes at Otsuka and now running your own business and are a board member of the Schizophrenia and Psychosis Action Alliance.
Holly Krasa: Sure, my interest in the brain started when I was really young. When I was four years old, I cut off a part of my finger in a lawn chair accident. And I was always very fascinated by just how distinct the memories of that event were and how curious I was about remembering the details of the sounds, the smells, the images, the events from that day, and really vivid detail even years after that injury. So that sort of started my interest in how the brain works. I initially started conducting basic research focused on the physiologic mechanisms involved in the production and release of neurohormones at labs at the University of Michigan in various research models and stumbled into industry like many, did 30 years ago because people don’t go to school often, and certainly didn’t back that to work in this field. But I stumbled into industry and medical product development when I responded to a newspaper ad for clinical research. I really didn’t know anything about the world or what actually job I was applying to. I worked at a CRO for a few years, conducting everything from non-interventional research and trials to supporting regulatory submission. From there I joined Otsuka in 2001 and I really joined ’cause I was excited about a late stage development program they had in place for an atypical antipsychotic, that regulated the release of dopamine, which is also a neuro hormone and neurotransmitter So, fit within my original interest area from a research perspective. At the time, Abilify was in late-stage development for schizophrenia. I didn’t end up working on Abilify when I first joined Otsuka. I actually spent my first decade there, working primarily leading different development programs in heart and rare kidney diseases. Otsuka was a really growing company back then, pretty small for some of these roles and didn’t have every functional area. So, my role there included all types of research, everything non-interventional natural history disease studies, clinical trials, all the way to cost effectiveness modeling and preparing evidence to help support products after approval. And during my time there, as the company grew, I sort of followed the products through the development phases and moves from, global clinical development into global medical affairs, and eventually then leading the health outcomes team for my last 5 years at Otsuka and of course we were responsible for your traditional health outcomes research and patient experience research, economic modeling, et cetera. But also, the associated evidence submissions were regulatory and payer authorities. And that’s when I was finally able to start working again directly in schizophrenia and during my time at Otsuka, I really learned, that the most impactful things we could do, was when we were involved in working with those living with the various conditions. and really listening to their stories. Either as volunteers in our research, or collaborating as part of a public private partnership across industry and academia and working with those that are living with the diseases. So, by incorporating those experiences, the biggest systems level change was possible. And so, I wanted to take that knowledge and bring it to kind of a broader community so that I could work at a higher systems level and have a bigger impact. And that’s when I decided to start, Blue Persimmon Group back in 2019 to help incorporate that lived experience more broadly throughout medical product development, health systems, research and policy working with both patient advocacy groups and industry. I started advising the Schizophrenia and Psychosis Action Alliance after they wanted to initiate a project that was focused on capturing and reporting the full economic and humanistic impacts of schizophrenia across all sectors of our society. This was really important because they were having challenges explaining to policy makers what was happening outside of the healthcare setting. So, while we were building that economic model, I had a wonderful opportunity to work closely with individuals living with schizophrenia, their family members, and people across different sectors. And, it was, frankly, shocked at some of the challenges faced by this community that I really hadn’t heard of. There are things that are addressable in other diseases and shouldn’t be happening. So, I joined the board of directors in 2001 so that I could work more directly with the community to address these really unnecessary barriers.
Mel Whittington: That’s excellent. There was a lot there. You’ve had a great career so far. When you were talking about the incident with your finger. I’m sorry you experienced that at such a young age. Ironically, my husband also cut off half of his finger a couple years ago. It is wild. I can’t tell you what I had for lunch yesterday, but I can tell you every single second of that experience. And so, is that because of these neurohormones? Is that why?
Holly Krasa: Well, there’s many different reasons why you remember traumatic events in very vivid detail. I’m not sure we know all of the reasons, but yeah, there’s, there’s a lot of different things that are involved in those memory pathways.
Mel Whittington: Okay. And it sounds like your interest in neurohormones is what sparked your interest in and your dedication to, specifically to schizophrenia.
Holly Krasa: I would, say early in my career, the basic science and basic physiology of what was going on, I found really interesting, but it was also really, just the complexity of the disorder and intricate relationships that happen between the chemistry and the brain, the structure and the associated behaviors, but particularly how such a debilitating illness could arise in subtle, yet significant disruptions and mineral circuits in the brain. My personal dedication to this population really evolved over the years by listening to the stories of those impacted, but also through conducting research that shows that failures within our current systems of care that are currently in place to support this population. I’ll tell you, there’s a lot of systems in place to support this population, and in spite of all of that and all the people trying to help, there’s a lot of inappropriate injustices and mistreatment of so many that are living with schizophrenia, that’s where kind of the personal dedication comes from. You know, once example I often share, and I, I’m very surprised by, having worked across many other health conditions, is that when people are told about the diagnosis, they and their families are often pulled by clinicians at the best they can hope for is to manage well enough just to minimize the number of significant relapses they have, but they are likely unable to have the same life that they plan originally, and they may never be successful at school at work or have a normal home life and just that common story I hear from families and individuals, is an unacceptable approach. It’s not what I would expect from the medical community, but I also understand why that’s been shared. We’ve overcome so many really significant challenges in health and what we used to think of as insurmountable diseases, we are now able to treat. so encouraging this community of researchers and clinicians, to imagine a world where there could be the equivalent here for schizophrenia is a really important thing that that I think would be most important. I’ve been really lucky in my career to work on first and disease treatments, um, where that same perception was there. People had a very difficult time envisioning what a different future would look like. For either patient families, but even the clinical community and, you know, with time and a lot of work and really dedicating yourself to solving those challenges, is a you’re able to see firsthand the change in perception and hope and even systems of care that come with even incremental innovation. For this community we need to do better.
Mel Whittington: We need to do better, and we’ll talk in a little bit more about innovation specifically for this community, but I, I want to note that you do use the word “community”, and I understand you work closely with and on behalf of people with schizophrenia, and um, you know, I think we can all hear your passion and your commitment in your voice, and so I was wondering if you could share some stories with us to help us better understand what living with schizophrenia is like.
Holly Krasa: Thank you for asking that question. I’m not sure I will be able to adequately describe this, but I will do my best. I’ve been really privileged to work with a lot of people who are thriving in school at work and their personal relationships, but also with those that are struggling every day. They share stories about when they first developed symptoms and when they were diagnosed. They share stories about being in hospitals and in jail. They share stories about finding the right care and the challenges. of doing that, but also, what it’s like when they do find something that works for them. But most importantly, I think they share a lot of stories of love, support, and recovery. And that’s what I always try and, try and focus on. From a, what it feels like to have schizophrenia, people often describe feeling very isolated and afraid. If you imagine, they start experiencing symptoms when they’re teenagers and young adults, when they’re just starting to work towards achieving goals and dream. They share that they often didn’t know what happened or why they were feeling the way they were feeling, they were either afraid to ask for help or didn’t know what was real to know something was wrong. As I mentioned, schizophrenia is kind of a very isolating disease. and the way someone’s explained it to me is, imagine feeling like you live in two worlds, being talked to by someone who’s constantly whispering things to you, shouting at you, or telling you what to do or how to feel. Imagine seeing things that may not be real. Feeling like someone’s watching you all the time, not trusting yourself or anyone else around you. People describe losing motivation to do anything. Or be around other people. And treatments don’t always help these negative symptoms. And some of them even make them worse while they’re trying to stop the hallucinations and delusions. People describe feeling numb. Sort of like watching their own life from outside, not knowing how to connect with others. Because these symptoms are often constant, people describe feeling exhausted and overwhelmed. But I think the thing that has impacted me the most from the stories is just how afraid they are. They’re afraid of what they might do, afraid of handling what others find easy, afraid of how they’ll be perceived, afraid of the future, afraid of relapsing and what that relapse might mean, being in hospitals, losing your job, your family, your home, being on the street, and many even experienced going to jail because of how society is treating us mentally. So, one other big area that that is also described to me is the worry about how the world, and their loved ones see them, and how this disease affects others. They describe challenges with current treatments, with side effects, things you’ve highlighted, like weight gain or uncontrolled movements. They describe the challenges that they’ve got getting access to treatments that they do want and issues with being able to meet the requirements to keep access to this really important care. They describe terrible stigma and biases associated with having schizophrenia. Whether it’s just simply that, that diagnosis, even if they’re doing well, there’s a lot of issues with how society, family, friends, healthcare providers, and really their own self stigma that they experience. And, if you can imagine being judged by others based on the worst time in your life, when you were very sick and needed help. Imagine if you get better, and everyone around you is just waiting or holding their breath, knowing that that same experience may happen again. Even after years of managing the disease, thriving in everyday life, people are often reminded of the times that, when they were not doing well, either by those around them openly or by the actions of those around them. So, it’s really important to remember that people living with, schizophrenia can find the right treatment and care programs. they are capable of managing these symptoms, live like everyone else, and thrive in their careers and relationships. But I think the most important thing to remember about these individuals is that they’re just people like you and people like me that are trying to do the best to achieve their goals in everyday life.
Mel Whittington: Absolutely, thank you for encouraging us. to remember that. It’s encouraging and exciting to hear that some do find the right treatment. And I think that’s great news, but how can we make it, so everybody finds the right treatment? And it does seem like innovation is still badly needed within schizophrenia and would you agree with that? And why is that?
Holly Krasa: I definitely agree with that and believe we are at a place right now where the true innovation that’s needed it’s possible. We really need different approaches and significant investment from multiple perspectives. What I’ve just described really leads to extensive economic and humanistic impacts. We’ve talked a little bit about the humanistic impacts, but from an economic perspective, unlike most medical conditions, the impacts of schizophrenia span across all sectors. It’s not just within the health care system or with families and the individual. Because our current systems of care are inadequate, you end up having, I think there’s over 314 federal programs that are supporting this population alone. So, at a societal level, these different challenges have enormous consequences. The symptoms, their downstream effects., the current response and treatment infrastructure often lead to individual struggling with issues, such as maintaining housing, encountering the justice system or difficulty obtaining or maintaining employment, even when they are doing well. This is something that we looked at in detail. A few years ago at the Schizophrenia and Psychosis Action Alliance, where in 2020, we developed a societal cost model where we estimated the excess costs of schizophrenia across all types of care and housing settings and really tried to look at things in a different way so that we could show if you are able to improve things, that you can move people out of jails and from being homeless. Or group homes into the community and how they might be able to thrive and function there from an economic perspective and any human perspective. So, just as one example, in most of these states, you’ll see that the direct costs are primarily within the health care system. In this case, our estimate was that about 30 billion dollars annually were spent in the healthcare system, but other direct costs relating to housing, homelessness services, disability income, incarceration, We’re higher than that at around 35 billion a year. So, we’re spending more indirect costs, provide care outside the health care system than we are within the health care system, which is a big problem, obviously. And, of course, when you incorporate indirect costs, such as reduced wages for those that are living in the community or other impacts like those on caregivers for unpaid care, they’re out of pocket cost to support their loved one or direct impacts on their health. The economic value of that less quality of life. Or shorten life expense and see and are well over 200 billion every year. More recent studies such as those that you’ve referenced in your report show that this is likely a significant underestimate for what the impact is. So that’s why innovations really needed is to address these problems. Why are those things happening, but why are we not treating people?
Mel Whittington: I think that’s what is exciting about innovation is that it can have an impact even beyond the healthcare system. And I think for schizophrenia in particular, where you just showed us with evidence that there is an impact on the healthcare system, but there’s a large impact on a lot of other health, on a lot of other systems and on society. And some health innovations can also have a meaningful impact on those. And so that is something that is exciting and something that should be evaluated and considered in my opinion.
Holly Krasa: I couldn’t agree more. The failures that we have at other levels we can correct those. We can address those. And finding treatments or care services that provide holistic care and address the whole person and not just a symptom are really critical. One of the main reasons why people have challenges staying on treatments are the side effects of those treatments. And it’s an area that we need to do better and continue to do work in finding treatments that are highly effective that it was all of the symptoms and impacts of dyspnea, but without that added burden of side effects that limit the potential efficacy of what we do have. a couple of areas, though, of innovation. We’re talking about care, but in order to get there, we really do also need to innovate and how we study the disease and how we measure efficacy for a lot of different reasons, there’s a very high failure rate in these clinical trials, even if the drug may work. Innovators expect to do 3 trials to get 2 that are positive because of these known issues. So that’s an area where we would also encourage innovation. Now, it sounds very doom and gloom right now, but I’m actually very, very hopeful that we can move things forward and continue to move things forward for this population. There’s a lot of brilliant researchers, healthcare providers, civil servants, policy makers that are working towards your solutions in this area. One example is The Accelerated Medicines Partnership, or AMP. Schizophrenia public private partnership that’s through the FNIH. That group is working towards identifying new assessments, blood and digital biomarkers with the objective of predicting the onset of psychosis, so we can intervene earlier and monitor symptoms more efficiently in clinical trials in the community. But to do this at a broader level, we really need an influx and investments in that area. And that investment in the core research. That’s needed, one example would be to start with the NIH. Where the annual budget for schizophrenia and serious mental illness research has remained flat for decades. So, in comparison to the average 200 million a year that the NIH funds in schizophrenia research since 2015, other disease areas like Alzheimer’s have seen exponential funding increases from 500 million a year up to 3.5 billion dollars in 2022. So, and I think we’ve all seen what that level of investment can do for innovation in that area. And that’s, that’s where investing in that foundational research at NIH and beyond is really critical to tackling this complex and impactful disease.
Mel Whittington: Absolutely. You mentioned highly effective treatments without the added burden of significant side effects. And I think that’s important for us all to hear that a treatment doesn’t cause additional issues or additional things that patients and their loved ones need to manage. What would a treatment that can reduce schizophrenia symptoms without the traditional side effects of antipsychotics, like weight gain, mean for patients? Because I am not as familiar with this community as you are, but it does seem like the commonly used drugs, you know, they’ve been great innovations, but they result in weight gain. Which can, you know, has, weight gain sounds like a, you know, a negative, annoying thing, but this translates into massive issues like diabetes, cardiovascular disease, and, and that’s only one of the side effects. And so, what would a effective treatment that doesn’t result in these side effects mean for the patient community?
Holly Krasa: Well so, the existing anti-psychotic medications that people have been working to tweak and innovate on over the last decades typically targets dopamine receptors, so that’s the mechanism that people have been working through for quite some time. The challenge is that dopamine is a neurohormone, and neurotransmitter that’s critical in many functions and is present in tissues throughout the brain and the body, such that these treatments cause several off target complications that are pretty significant, but they also vary by treatment and individual, and there’s not a great way to predict who will respond in what way. So, side effects, as you mentioned, like weight gain with the associated, obesity, diabetes, and heart disease, motor disturbances, feeling sedated, and other impactful issues are very, very common with these treatments. And that makes it difficult for people to want to stay on these treatments. So, because these side effects are so frequent, they also can increase self and experience stigma, cause a lot of mental and physical anguish. So, the consequence of stopping a treatment in this situation is different than in other states. These medications take a while to work. So, stopping a treatment or transitioning to a medication, a new medication to see if that works or is better from a side effect perspective often leads to worsening symptoms, repeated hospitalizations and other disruptions, like we’ve neem talking about. But I also want to expand your question a little bit to go beyond side effects. It’s really important that we also find treatments that don’t just reduce positive symptoms. So, the symptoms of hallucinations and delusions that people often perceive. We’re looking at treatments that can adequately address all the symptoms of schizophrenia, including the negative and cognitive symptoms with the disease state. So, to explain why these are important, cognitive or passive symptoms, such as low motivation and difficulties expressing emotions are the strongest predictors of outcomes. Such that the ability to work or socialize are impacted, and as mentioned, these are not currently well addressed by traditional anti-psychotic treatments. So, I would say any new treatment that does better, at addressing all symptoms and impacts of schizophrenia that doesn’t create chronic health issues, such as obesity or heart disease, would really enable this community to recover and thrive more effectively. And I don’t think I’m understating it when I say that a treatment that does all of these things would be priceless for those that are living with the diagnosis for their families and for society overall.
Mel Whittington: We saw that a little bit in our Cobenfy report and obviously there was a price assigned to the drug, and a price ended up having to be paid but looking at its impact on the healthcare system was only such a small piece of its value proposition, looking at what it does for patient productivity and caregiver impact, and, other outcomes for society as a whole, the price ended up becoming great value, cost saving to society in our analyses. And so, you know, all comes back to those economic burden estimates that you’ve researched and published and talked about and, you know, when a condition has such an impact on so many sectors, it’s so important to then evaluate innovations on those different sectors. When you were talking, I, I, you know, was kind of stewing on, I keep calling it side effects, but these really are additional chronic health issues. You know, like when I hear side effects, I think of, you know, maybe something kind of transient, a little nuisance, but this is becoming a whole new chronic conditions like diabetes and, cardiovascular disease and Tardive Dyskinesia and, you know, so I’m just thinking about there’s already these symptoms that you talked about that are important to manage with effective treatments, but then to add on additional chronic conditions, that just seems overwhelming and something we need to do better.
Holly Krasa: Absolutely, and I appreciate you highlighting that they are additional medical conditions. One of the challenges we have with this population is our kind of 2 system health care system where behavioral conditions are in one and physical conditions are in another, even though they’re all physical. So that when you do have a treatment, or the treatment for schizophrenia causes other chronic health conditions, that integrated care approach is a lot more difficult to achieve in this population.
Mel Whittington: You’ve also mentioned the families and I’ve talked a little bit about caregivers as well. In our report, we cite your great work on measuring the impacts of caregiving and schizophrenia. That’s how I was introduced to you is stumbling upon that great work looking at the impacts beyond the healthcare system and beyond the patient, but to the caregivers. And do you have any stories you could share with us from, caregivers of people living with schizophrenia?
Holly Krasa: I’ll do my best on that one as well. So first, thank you so much for highlighting that work on that that we did a few years ago, looking at the kind of expanded impact that this population of caregivers’ experiences on a daily basis. We decided to do that study after hearing stories from caregivers that told us about the different impacts that they were experiencing. And they were not things that were described in the literature that we quantified. So, from these everyday discussions, it was clear that caregivers were serving in the place of what could be provided by other systems, in order to ensure that the necessary care and support is in place for their loved ones. I would encourage everyone to look at those types of costs that are listed in that study because it’s quite surprising how much people are spending on things like legal services to defend their loved one who was a victim of a crime while they were experiencing symptoms. Or to really work through the court system. Or even spending money on everyday necessities and providing that type of care. Schizophrenia is really just a very cruel disease in that the symptoms start in adolescence with a diagnosis occurring in the late teens or early twenties when people really have their entire lives ahead of them. If you imagine at least two kids in every high school graduating class in the U.S. are going to be diagnosed with schizophrenia. Now imagine you’re their parent, watching your vibrant and capable child struggle in school and then withdraw socially. You may see them self-medicate with drugs and alcohol and not know what they’re doing or understand why they’ve turned to those vices to help manage the symptoms that you’re not aware are occurring. The diagnosis of schizophrenia also is quite complicated and not made formally until after there’s evidence of symptoms and persistent disturbance for at least six months. So, if you imagine being a parent or a sibling and seeing your loved one with these issues and not knowing how to help while you’re working through this process, trying to find somebody to help. Family members often talk about the time when their loved one was in the hospital and a compulsory care program that they had to enforce on their loved one or when they got a call from law enforcement and just the fear and uncertainty and guilt that they experienced from that process. They tell us of stories of not being able to convince their family member that they even have anything wrong with them, or that they need help because one of the symptoms. Or consequences of having this disease is that not everyone with schizophrenia is able to recognize their symptoms or even that anything’s wrong. Caregivers tell us stories of trying to find someone to help and not being able to find a doctor, or finally finding a treatment that works and insurance changing what treatments they’ll pay for. These things can cause unnecessary and impactful disruptions in care. Many of the most difficult to treat, individuals who have been through many different treatments and not found something that works might eventually find something, but then need to go through weekly, to monthly blood testing, which is a challenge in this population for many reasons, and then that blood test result has to work its way through a complicated system so that the drug can even be dispensed for weekly or monthly to that patient. So, supporting a loved one with schizophrenia, who’s already struggling, to get over these barriers is sometimes impossible, but always described as exhausting. But I will also say that in spite of all of these challenges, caregivers describe stories of resilience, persistence, and show the limitless well of love that they have for their affected family member or friend. I can’t do either, the parent, the patient, or a care partner stories proper justice, and I will highlight that it’s National Family Caregivers Month, and SMPA is currently highlighting caregiver stories on our website. So if you go to sczaction.org, you can read these stories. They’re very impactful. I’ll say while you’re there, you could head to the research section and there’s a report from a 2022 extremely led patient, patient-focused drug development meeting where you can hear directly from patients and their families.
Mel Whittington: Thank you. I’ll check that out. I hope those listening will too. I want to pivot a little bit to kind of your experience in industry and your experience leading teams dedicated to developing and commercializing products in mental health conditions. And how is developing and commercializing mental health treatments different than other therapeutic areas?
Holly Krasa: This is definitely an evolving and unique area. As I’ve mentioned, we have different systems of care in the US and this creates barriers for individuals trying to access care, but it also makes it more difficult for innovators to reach this population because the traditional ways to get to people who are affected by disease and clinical trials or in the real world are not the same and a lot of this population doesn’t even have good access to experts or people who are really well trained to provide care so that that creates kind of a unique balance for development of treatments in this area. Clinical development programs have also been measuring advocacy by certain scales for many decades. And as mentioned, those trial designs result in very high failure rates because the placebo groups also improve when you get somebody into a good, structured care system. So, companies have created a lot of different approaches to help manage that placebo effect, including extensive run-in periods and treatment with for all designs. But those haven’t been able to overcome some of those challenges, which is why you will often run more studies than you would typically need to do in other areas.
Mel Whittington: Interesting.
Holly Krasa: Now, I should also have stated earlier that currently available antipsychotics do work for many people, and researchers spent receptor binding profiles to help improve efficacy of treating symptoms while reducing potential side effects and in many cases have done this successfully.
Mel Whittington: Great.
Holly Krasa: The challenge of using the same end point that are fairly insensitive to detect the unique profiles. of these drugs and how they are potentially better for one person versus another continues the complexity of this, this condition and what’s really happening in the brain at any point in time in any individual is really hard to go. When you’re looking at aggregated clinical trial data, and the same goes for side effects, because obviously the side effects that we’re talking about don’t happen in everybody. They’re just very impactful when they do. So, in the real world there’s quite a bit of trial and error to find what works for each person. And that impacts how these treatments are commercialized because the same issues with development, There’s complications of identifying and reaching the people that are most likely to benefit from your treatment also exist. One thing I want to highlight as well is that we often hear about issues in this population relating to adhering to their prescribed treatments. Adherence is really not that different than you see in the real world in any other chronic medication situation and other disease. The difference is really the consequence of stopping a medication or having an interrupted interruption is, um so much more impactful here. So, to address the issue of reaching those that need treatments, it’s really important that policymakers, healthcare providers, industry work together and industry has developed many wraparound support programs and products and there is quite a lot of collaboration going on in this area. Which I think is really important and it’s, it’s a very creative group of innovators that have been working to try and solve this problem across the spectrum.
Mel Whittington: That’s great. You mentioned adherence and in our CPE Exclusive on Cobenfy, we attempted to assess how Cobenfy might impact adherence as adherence was one of 24 value elements we looked at and interestingly adherence was the only value element we assessed the innovation as having a neutral impact on and with the thought that, okay, it’s a twice daily pill regimen. So, there might be less adherence as compared to some once daily regimens, but then again, there’s these fewer side effects, which I’m not loving using the word side effects anymore, but there are fewer side effects that could therefore increase adherence. So, we actually gave it a neutral rating on adherence. For the other 23 of 24 value elements, we actually evaluated it as having a likely positive impact on those. So, what makes Cobenfy so different from other treatments for schizophrenia? And is there a lot of excitement?
Holly Krasa: I would say from the simplest perspective, the biggest difference, of Cobenfy is its presumed mechanism of action. I’ll just start at that level where,
Mel Whittington: The neurobiologist.
Holly Krasa: Yeah. Yeah. But it’s important to understand, Cobenfy works as an agonist at two receptors. The M1 and M4 muscarinic receptors without directly impacting the dopamine receptors, which is unique. It’s also unique that this product combines two different medications. One that is targeted to treat the symptoms of schizophrenia and the other that was added to minimize the off-target side effects of the first. Now this isn’t a unique approach from the perspective of how some clinicians are working to provide integrated care for the community. For example, some clinicians prescribe Metformin or a GLP one to limit the impact of weight gain when they start an existing antipsychotic and have seen great success. But this is not done consistently by any means. And creating that integrated treat the whole patient approach, is something that is unique about how Cobenfy is designed because it is working to tackle both sides of treatment. Now, the other part is because Cobenfy’s mechanism is different. As you’ve mentioned, the reported side effects do appear to be different than what is seen with many other anti-psychotics. And you highlighted this in your report. The evidence of weight gain and other metabolic side effects so far seem to not be an issue in fact some of the data reports that most people actually lose some weight while they were in the in the trials, which is really encouraging. Of course, there are side effects, but I think the word side effect fits in this situation where they are primarily GI side effects like nausea, and they appear to be manageable for most, which is a very important thing. The other unique thing that’s very encouraging from the data from these trials is it suggests that Cobenfy may improve cognitive, negative and positive symptoms. So, really treating the whole spectrum of impact for this population and, and really for the first time in decades, it’s a truly new mechanism treatment has been shown to be effective. Which should be really encouraging about the potential for innovators and that trying these new approaches is worthwhile. So, of course, it’s still early and there’s limited data. And the important evidence so far is very encouraging, supporting efficacy for all of the importance, the symptoms with side effects that can be managed, and of course, we need more data, more research and, real world use to really show what the broad impact is to individuals and society, but your report’s done a very good job at envisioning what that could be.
Mel Whittington: Oh, I love that. Thinking a little bit more about our report in our CPE exclusive on Cobenfy, we did attempt to evaluate the potential societal impact of Cobenfy, of what could be quantified. You know, hearing from you in this conversation and many other conversations I’ve heard with you, I fully acknowledge that we cannot quantify everything, but we can quantify some things. And so that’s what we attempted to do. I would love to hear from you about kind of what we got wrong or what are things that we didn’t capture quantitatively. I think we’ve already heard some of that but would love your feedback on a report as we think about doing these again in the future.
Holly Krasa: So, first, I want to start with what you got right in the report. Most importantly, you didn’t only look at direct health care costs and closely related traditional cost effectiveness approaches. With so much of the impact of this condition not being within the healthcare system and something you can capture through healthcare resource utilization or traditional cost-effective modeling approaches, it’s really critical to incorporate as many impacts as possible, which is something that you’ve worked towards in that report. Given the complexity of the system and services that support this population, I also thought it was very appropriate at that you focused on showing that even addressing one side effect, such as weight gain can have enormous impacts. So, sometimes when you combine a lot of things into these models, it neutralizes what you’re looking at and It’s hard for people to understand. So, I actually thought that was a very interesting approach that allowed us to look at what just dealing with one thing and there’s many other, aspects of a treatment that could be considered, from a comparative perspective that would allow you to understand the broader impacts of associated with treatment that could be assessed. So, housing and impacts of that could be carried through other sectors would be helpful to be able to include. However, I know from personal experience doing research in this area, there’s very limited data in that in those areas. So, that would be a future modeling approach as more data is available to really focus and look at impacts across different sectors. So, I would say it’s really just important for researchers to continue to work to address the evidence that we do have, on the impacts of schizophrenia, including the associated costs across these sectors. and then you will be able to better see how Cobenfy or other treatments in are important.
Mel Whittington: That’s really good feedback for us and for the industry, and I agree completely. Researchers can and need to continue to address the evidence gaps so we can quantify additional things. But I think we also need to recognize that there will always be things that can’t be quantified. Not everything that counts can be counted. And that’s why I’m so grateful for people like you who are willing to help us round out that message and discuss those things that will never be quantified. Holly, I have enjoyed this so much. Before we close, we always like to ask one final question, and that is, what is the best piece of advice you have ever received? You’ve given me great advice but I would love to hear what is the best piece of advice you have received?
Holly Krasa: Okay, so the most impactful advice I’ve ever received throughout my career is to do the right thing and the money will follow. If you follow the science, and you follow what people really need, if there’s a real need out there and you’ve listened to why somebody needs something, and then you allow your researchers to really go after it and don’t worry so much about what the current world thinks is possible and you envision a future. At a minimum, you’re going to help people. But, in my experience, when you follow that philosophy, there is always reward at the end. And, that’s really kind of the foundation of the concept that that’s been so well, and I’ve seen play out my career.
Mel Whittington: Oh, wow, Holly, I love that. Thank you for joining this podcast. I think you’ve perfectly illustrated that we can try to capture some things in an economic model and in a report. And I’m a health economist. I try really hard to you know, try to get as much into those evaluations as possible. But, that’s not possible. We can’t fully quantify value. We can’t fully quantify impact. But we can hear from people. We can hear from people like you to round out that message and to understand what we can quantify and what we can’t quantify. And in my world, I spend a lot of time behind a computer in Excel spreadsheets using math and numbers, but it really isn’t about math and numbers and Excel spreadsheets. We really are talking about real people and so I thank you for coming on to this podcast for helping us remember those real people and keeping them in mind and at the forefront of our decision making. We need to hear their stories and their lived experience. Do you have any closing words?
Holly Krasa: No, just thank you so much for highlighting this particular population and the community and allowing us to have a bit of a voice here to help round out what those numbers mean.
Mel Whittington: Excellent. Thank you, Holly.
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