RARE REV-inar episode 004
Evolving treatments for Gaucher disease webinar : Understanding gene therapy
Welcome to the fourth in our series of rare webinars. Today we’ll be talking about the evolution of treatments for Gaucher disease and understanding the potential for gene therapy. I’m Nicola Miller creative director at RARE Revolution Magazine and in the background joining me on the tech today our is Becky Pender, who always does a great job. So thank you, Becky, for all the back of house bits you’ll be doing. Today’s session is a partnership with Prevail Therapeutics who are committed to developing gene therapies to slow or stop the progression of neurodegenerative disease. Just a couple of housekeeping points if I can. We’ve got a great panel on today so please do take advantage by asking questions in the q&a chat box so that we can pick those up at the end. Also, if there’s anything that we don’t get to durperipherallying today’s session, we will endeavor to answer it and feedback to you afterwards. I’ve just popped up a little disclaimer there. So please do just take a few minutes to read that just essentially to say that this is a discussion today for education purposes, and not in terms of providing any medical advice. So if you can just take a few minutes to read that that’d be wonderful. Today’s session will also be available to revisit on demand, and will circulate the links to everyone that’s registered in due course. I’m really thrilled to be joined by a very knowledgeable panel today we’ve got co president and co founder of the Gaucher Community Alliance and Gaucher patient herself Cyndi Frank, hoping to be joined shortly. I think he’s running a little bit late as Dr. Neil Weinreb. M.D. who is the regional coordinator and chair of the international collaborative Gaucher group at the University of Miami UHealth Sylvester Cancer Center. Quite a mouthful there. And Jeffrey Sevigny, M.D. chief medical officer at Prevail Therapeutics so Hello all and welcome. Jeff, I’m gonna come to you first please for an introduction. If I can get just pop your your camera and mic back on there, Jeff and then I know you’re gonna do quick hello.
Yeah. Hi. Thank you. Thank you for the introduction and good morning and welcome everybody. My name is Jeff Sevigny. And I’m here on behalf of Prevail therapeutics. In which first to start firstly, we wish to start by thanking revolution team for partnering with us in Oregon in organizing venues like this. It’s really venues like this that help companies like Prevail share valuable information. Secondly, I want to thank Cyndi Frank for joining us. It’s important to get her insights about the disease and some some things that we’re trying to work on to fill unmet medical needs. And also hopefully we’ll be joined shortly by Dr. Neil Weinreb. So a little bit about myself, I’m the chief medical officer of Prevail Therapeutics, and I’m here to and proudly representing the passionate and dedicated research and development team at Prevail. I’m a physician scientist. I spent most of my career in research and development and seeking innovative ways to treat people who have unmet medical needs in both rare diseases and more generic or sporadic diseases. Prevail Therapeutics is a relatively young company started in 2017. Its mission is dedicated to developing gene therapies which we’ll talk a bit more about as we get into the conversation for for rare diseases in particular ones that affect the nervous system. It’s based in New York City. And we currently have over 100 people that work for us. Very recently, we started recruiting people for a phase one two clinical study. For patients who have Gaucher disease, the study is called Proceed. You’ll hear me refer to this trial, the Proceed study to Proceed trial. And this is testing an investigational gene therapy that transfers a healthy copy of the GBA1 gene into the cells of the body. Once in the cell, this gene encodes the enzyme glucose riversides. And this is the enzyme that is deficient or lacking in patients that have Gaucher disease. And we’ll talk more about that later about how this works. But one thing I want to mention now is what’s unique about gene therapies is the promise that it holds is still to be tested is that it can be a one and done type treatment. That is you get one intravenous infusion. And the idea is that this would treat the disease for the remainder of that person’s life. The study is now open and we are screening patients with type one Gaucher disease to enter the study. We have a site in Virginia that’s recruiting patients, and we will soon have additional sites in the United States and ultimately, there will also be sites in Europe. I also want to point out that this is not the first time we’ve tested this investigational gene therapy for Gaucher disease. In fact, we have a study that’s been open for well over a year, that’s testing the same construct in patients that have type two Gaucher disease. This is a very severe neurological form of the disease. And we started in that population, because that’s where the highest unmet medical need is. So we do have experience with this gene therapy, and now we are starting it and patients with type one Gaucher disease. So I look forward to having a deeper discussion with both Cyndi and hopefully Dr. Weinreb. And with that, I’ll turn it back over to you.
Wonderful, thank you so much, Jeff. Great, so let’s let’s dive in. But let’s go right back to the basics here. Can you just explain, Jeff, what is Gaucher disease and what are the different types?
Okay, sure, yeah. So, you know, Gaucher disease is a genetic disorder, people are born with it. And it’s because of a having it’s because of a mutation in the gene a gene called the GBA1 gene. So patients who have mutations can develop a spectrum of diseases that we call Gaucher disease. The most common form, and the one we’ll be speaking to predominantly today is called type one Gaucher disease. And this is a disease in which there’s a deficiency in the enzyme glucocerebrosidase. And it leads to a swelling of several organs in the body, particularly the liver and the spleen. So they develop splenomegaly and hepatomegaly. And then these organs trap blood cells, and therefore they develop problems with platelets and anemia. So it’s sort of a secondary effect of the disease. Other other organs can also be affected, including the bones, bones and lungs, it’s a bit rare, but the most common clinical manifestations are with the spleen and in with the, with the liver. That’s the most common form. Much rarer forms are what we call the neuronopathic forms. And these are type two and type three Gaucher disease. And it all relates to the severity of the mutation and the amount of the enzyme that’s present. And in these patients that have type two or type three, they have far less enzyme, and they develop neurological symptoms. The most severe is actually type two, and these are children. These children are born with severe neurological deficits, as well as the peripheral symptoms that I mentioned earlier. And then type three, unfortunately, the the numbering is not in great order here, type three is less severe than type two. And these are people who sort of fall between type one and type two, but they still have neurological symptoms. And their symptoms tend tend to develop a little bit later in life and to be more slowly progressive. But fundamentally, it’s a problem starts as a problem with a with a gene that has a mutation that leads to an insufficient amount of an enzyme. And this leads to problems in certain organs of the body.
Great. Thank you, Jeff. And what does the current care pathway look like? And what are the particular challenges with that standard of care for GD1, which is you mentioned is the most common form.
Yeah, so there are treatments that are available and they’ve been available for, I don’t know, maybe 20/30 years, the standard of care treatment is something we call enzyme replacement therapy. So as I said this, this gene mutation leads to a defective enzyme, and this therapy replaces the enzyme directly with an intravenous infusion, there are several products that are available that are marketed in which these, this enzyme is infused into the body. So this is the I would say that the standard of care, it’s effective for most people, it does a good job at treating the liver and the spleen, it’s not so good at treating necessarily problems in lung in the lung or in the bones. And it’s totally ineffective at treating problems in the brain. And that’s because it doesn’t get into the brain, you give it peripherally. It has a very short half life. So once you give it peripherally, it gets into the organs in the peripheral organs. And it does its thing, but it just cannot get into the brain. And that’s why the greatest unmet need in Gaucher disease is actually for type two and type three for the neurological symptoms. So that’s the current standard of care. It’s effective. It’s an IV infusion. And generally speaking, people have to have these IV infusions every two weeks, sometimes every four weeks, but it’s a lifelong therapy. So you’re really tethered to an IV for the remainder of your life.
Thank you so much. Yeah, so it’s a really big long term commitment for, for patients. And so let’s, let’s bring you in then Cyndi. And it’s really important to think about the lived experience here. So can you talk us through? You know, I know, it’s a big topic in itself, but you know, what is it like to live with Gaucher type one? And, you know, what are your biggest challenges?
Yeah, thank you. Um, you know, sometimes it’s easy, and sometimes it’s hard. So I was diagnosed with Gaucher, when I was 13, after about a year of going back to the doctor several times a week to have blood drawn and to try to figure out what was going on. So, you know, this was back in the 1970s, when there was nothing online and being diagnosed with a rare disease was was incredibly difficult. So, you know, good news. It’s not leukemia, which was one of the original misdiagnoses and, and it’s Gaucher, but back then there was no treatment. And there really was no hope. And it was predicted that I would be using a wheelchair by the time I was 20. And that I wouldn’t live past 30. And when I was 28, treatment became available. And I actually was in that initial trial to get the first treatment approved and it changed everything, it changed my life. I really separate my life between pre treatment and post treatment, because I lead a pretty normal life now. And you know, I’d like to say it doesn’t solve everything for me personally. Sometimes, I’m a little confused when type one is called non neuronopathic, because in my family, we have Lewy body dementia, I have neuropathy. So there are still a lot of things going on that this treatment, that the treatments available are not satisfying. But for the most part, I work and I give back to society, and I hike and exercise and I enjoy, you know, a pretty beautiful, normal life.
Wonderful, that must have felt quite overwhelming, you know, being given that kind of timeframe and then approaching 28, did you really have a sense of the sort of ticking clock or, you know, how did you feel about that time running up to that?
Yeah, I think it was beyond a ticking clock. I was very sick in my 20s. I was in the hospital. And as much as I was out of the hospital, my spleen had grown to 20 pounds. So I looked pregnant for 10/15 years of my life. I couldn’t walk up a flight of stairs. If I sneezed, I got nosebleeds for four or five hours. I had to get blood transfusions when I menstruated. I mean, it was it was a different life. So yeah, the clock was ticking. And I was incredibly sick. And I think when I had an incredible amounts of bone pain and bone crises and fatigue, and I, you know, it’s interesting, when you’re that sick, on some level, you just want relief, and you don’t care how? Absolutely.
So what would you say are the kind of the greatest challenges for the community as a whole? And what are the kind of underappreciated or the under-represented elements of the disease that perhaps people don’t realize? I mean, you’ve mentioned quite a few things there, you know, just don’t you know, that nosebleeds and, you know, having to have a transfusion through your menstrual cycle. That’s, you know, there’s a quite impactful things, but what would you say are the biggest challenges for the community as a whole?
Unknown Speaker 14:18
Well, and I speak as a representative of the Gaucher Community Alliance, so I co run a patient organisation and through that we’re able to, we really reach out to the patient population constantly to find out what their unmet needs are. And then we communicate them with industry and with the medical experts so that the three of us together can figure out the best ways to address these. I mean, of course, the biggest problem is that there’s no available treatment that crosses the blood brain barrier. The type two and three patients, they suffer way beyond how I suffered when I was younger. The cost of treatment is incredibly challenging. The cost of insurance and copays. You know, it’s, it’s hard to even find guidance on what type of insurance you should get if you have a choice, because you need to get something that’s going to cover your treatment. And there is no perfect treatment. For the treatments that are available, there are still side effects, there’s still symptoms that are not treated. Mental health can be a big issue, especially during COVID that got compounded, you know, there’s isolation, depression, fear. And so we feel as a patient organisation, it’s incredibly important to create networks, and to create ways that patients can, can support one another, communicate with one another. And, you know, really make lifelong friends that you can live with someone you know, someone that understands what you’re going through a testing in the community is also a challenge, we get calls all the time, from people who they research, they think they might have Gaucher and they can’t get a doctor to order test, which is incredibly surprising. And I think what’s really the most underappreciated about all of this is the cost of drugs, and that cost, how it affects almost everything in our lives. Because if we don’t have the funds to pay for that insurance, we’re not getting treatment, and we’re not gonna survive.
And that’s paralyzing socially as well, isn’t it and economically because I assume that moving jobs and you know, career progression can be really limiting? If you don’t want gaps in your insurance? You know, you’ve got to take that into consideration, isn’t it in terms of what you might do career wise, and how you might move laterally or up in different jobs?
It has dictated every job I’ve ever taken in my life. The first thing I do is I ask about that insurance policy. And I, I look into it, and I research and I see if I’m going to be covered. Yeah. And know also, my entire life, both my husband’s and my husband and I have put money aside every paycheck into an account. Because I know that this, you know, I know this disease is going to cost me a lot of money. Once I go on Medicare, and once I if I ever want to travel or it, it dictates everything.
Yeah. I think that it’s often the financial side is often the unseen burden that you know, perhaps we don’t see we’re very focused on the physical and maybe even the mental health. But actually, that’s that’s such a big factor, isn’t it? Dr. Weinreb, thank you so much for joining us.
I apologize. I just could not get in, eventually. Yeah.
Okay. Sit back and relax and settle in. And we’ll get we’ll get to you soon. So Jeff, if we can have a look at from our sort of scientific lens here as a CMO, what do you see as the greatest opportunities for research and development into this disease?
Unknown Speaker 17:43
Well, I think it all starts where where the unmet need is, and that’s why we we got involved with with Gaucher disease so. And the biggest unmet need is for the neurological symptoms, because kids with type two or type three have no no treatment at all for their neurological symptoms. There’s just simply as no therapy available, children with type two, usually pass away within one to two years of, of life. So it’s a real devastating disorder. And then people will take three, the disease can be more stable, but it can have, you know, cognitive issues, development issues. So so that’s where the biggest unmet need is, in fact, that’s why we started in type two and three, but also point out that one of the major risk factors for Parkinson’s disease is carrying one of these GBA1 gene mutations. So so that’s another big opportunity and actually something that we’re developing this, this investigational therapy for, are for people who have GBA mutations in Parkinson’s disease, again, it’s a it’s a neurological manifestation of the disease, and they’re just simply as nothing to treat their neurological symptoms. So that’s, that’s another big opportunity.
And presumably, the increased numbers brought about by that helps as well, because you’ve got more sort of have a bigger cohort if you’re able to look at another disease as well.
Exactly. That’s, that’s an important consideration. Now, in type one Gaucher disease, there are there are also opportunities and you know, Cyndi mentioned some of these so number one, while the current standard of care therapy are wonderful, and for many people, they closely or come close to curing the disease so long as they take therapy every every two to four weeks. There are some some people whose symptoms do not abate with the current standard of care for whatever reason, maybe their their liver size or their spleen sizes and come back to normal. Or I’d say maybe more commonly, they still are left with problems with their bones and they have bone crises or problems with their lungs. current standard of care, not very good at treating those those manifestations of Gaucher disease. Um, And then of course, it’s the convenience issue, current standard of care requires infusions again every two to four weeks. And I think one of the one of the opportunities is to is to liberate patients from this type of, of treatment, and potentially provide them with a one and done approach versus a single infusion that could treat their disease for many years.
Thank you so much. Now, Cyndi mentioned her involvement, obviously with it, the patient organisation, which of course, are pivotal in any kind of research and moving things forward. So what role does patient engagement play within Prevail? And have you got examples of kind of how you engage with the patient community to develop the work you’re doing?
Yeah no, patient engagement is critical to our success. You know, firstly, it helps us understand the unmet need. We rely on patient engagement to understand what their issues are, what patient issues are, what their families and caregivers are going, going through. And, you know, this is important, because this is not something we can glean at medical conferences or reading papers, you know, that’s often where we get our scientific information. But that’s, that’s not really there. So you really hear the the emotional stories and the pain and suffering that these patients go through. So we have to rely on patient engagement to understand this. And, and we also learn about the experience that patients go through when when we conduct clinical studies. So it’s one thing to conduct the perfect clinical study, to try to answer a scientific question, but it’s another to run a clinical study that is that is patient focused or patient centric. So it’s so the study which which can be a bit onerous for patients, because it requires multiple visits to follow up on many, many of the outcome measures. But it’s important to understand what they’re going through to help us make our, devise our protocols so it’s a pleasant experience for patients. You know, that’s that’s the real-world example. So we reach out to we use patient advocacy groups to connect with patients. They give us feedback about what their, what their needs are. And the real life example here is that the biggest unmet need and here we are, in our clinical study, we decided to start where the biggest unmet need was, and that’s in Parkinson’s disease and in patients with type one or excuse me, type two Gaucher disease. And then secondly, we’ve we’ve reached out to patients and through patient advocacy groups to understand what their experiences are, and and participate in clinical studies. And this has had a direct influence in how we have written our protocols to try to make the experience better for the patients and the caregivers.