Evie's Story Revisited

Evie: I'm short, but I feel like I have to work harder than other kids because my body works differently. It has also taught me that I'm strong and I can do anything I put my mind to. Now that I'm older, I hope that other kids see that their shots are helpful and that they can grow stronger, like I have. Todd: Hypophosphatasia, also known as HPP, is a rare genetic condition that affects bones, breathing and mobility. The exact prevalence of HPP is unknown, but in its severe form, it's expected to affect one in a hundred thousand babies. The disorder affects mineralization, the process by which calcium and phosphorus are deposited in developing bones and teeth. Instead of strong and rigid teeth and bones, an HPP patient's bones are soft and prone to fracture odeformity. Oftentimes, HPP can be detected before birth. This was the case for a special girl named Evie, whose parents did not know what her prognosis might be. That is until shortly after Evie's birth, when they were offered a life-changing chance to participate in a clinical trial for the first prescription treatment for HPP. When Evie was eight years old, she met for the first time, some of the researchers from Charles River and Alexion, who worked on the treatment for her ultra rare disease. Now, age 13, Evie and her mother, Lindsey, join us for today's episode of Vital Science. We'll discuss Evie's treatment journey, the important role of community for rare disease patients, and how Evie's participation in the Strensiq trial has changed not only her and her family's lives, but the lives of many with HPP. Gina: It's not often that we have the honor of speaking with a patient, so Lindsey and Evie, I want to thank you both for being here and welcome to Vital Science. Lindsey: Thanks for having us. Evie: Thanks. Gina: Yeah, absolutely. So Lindsey, I'm going to dive right in here and ask you a couple questions. It's been a while since I've seen both of you, and I'm really excited today to hear more about your lives and what's been happening. Most importantly, how has Evie's diagnosis shaped your family and your role as a patient advocate? Lindsey: Yeah, Evie's diagnosis has shaped most aspects of our life since she was diagnosed. Our day-to-day looks different. Our goals for our kids are different. How we view their futures are different. We weren't supposed to have very much time with her, so we get to have a little bit higher level of gratitude, I think, for some of the little things. We didn't know if she would walk and she's walking and running and playing sports and doing all the things, so it's shaped us a lot. And then as a patient advocate, I think I probably have a keener eye for people with disabilities. It's important to me that they get their questions answered, that they know how to advocate for their kids, for their family members, and that it's important to fight for the cure that they need. So it's hard work and it's worth it and that's about it. There's a lot of conversation that happens on the HPP pages where people will say, "My child's struggling with this," or "Has anyone had craniosynostosis surgery?" "Have you dealt with Chiari malformation?" And I do feel like we have a pretty strong voice there because Evie's done so well. The surgeries that she's had have been really successful. Right now, she's in physical therapy, not as a surgical remedy, but because I want her to be able to mechanically walk in the way that's going to benefit her body the most. So I found a physical therapist who could work with her on core strength and leg movement and what stretches do we need to do to keep you from being stiff when you wake up in the morning? So as she gets older, I think it's going to be a lot of, how can we help you live the best you can in the body that you have? Gina: So Evie, it seems like yesterday when we first met you, I believe you were eight at the time, and I can't believe you're a teenager now, 13 years old. What grade are you in now? Evie: I'm in seventh grade. Gina: Okay. And do you have a favorite subject in your schoolwork? Evie: I like math. Gina: Great. Math will take you anywhere, I think. What about swimming? Is that something you're still doing? In our early days, we shared some time with you in the pool. Is that still part of your life? Evie: I don't do swim team anymore, but I just swim for fun. Gina: Perfect. I love it. So we don't need to be on the Olympic training path here. We can just enjoy the pool. Have you thought about what you want to be when you're older and what things interest you or what your future job could even be? Evie: I want to be a travel nurse because I love traveling and I love helping others. Gina: So it combines both of that. That's amazing. Good for you. Lots of school, but the math will come in handy for that. So Lindsey, Evie's relationship with Charles River began when she was quite young. I'm just wondering if you could take us back to that time and walk us through your journey at that time. Lindsey: So we found out Evie had a bone disorder when I was pregnant. We didn't know what it was. They found it really early on, so we knew that it was going to be severe. They told us the earlier they find it, the more severe it is, and they saw it on her very first ultrasound. Evie was misdiagnosed with OI, which is osteogenesis imperfecta, and she was diagnosed with type two, which is a lethal form, but she was not expected to survive long after birth, if she made it through delivery. So we sort of prepared for that for months. We also prayed that she would make it and do really well, and she did. So she was born. She made it through delivery, and after a few days in the hospital, they sent us home. It was clear that she had something. Her limbs were short and a little bit bowed. She had some labored breathing, but they didn't have any other reasons not to send us home. So they sent us home. A few weeks later, she started having seizures. What that looked like when she was little was she would stop breathing. We would have to try to get her to come back to. When we took her in to our children's hospital, they diagnosed her with hypophosphatasia. So we got really lucky. We ended up with a doctor who had heard of HPP at a rare disease conference. He noticed that her alkaline phosphatase was undetectable in her lab draws, and she was diagnosed with hypophosphatasia. So at that same hospital stay, they told us that there was a clinical trial that she might be eligible for. It wasn't for sure. Then she started that trial when she was three months old. So our first few years, she had lots of surgeries. I think were at 13 total. She had several on her skull. Her skull fused a little too early, which is called craniosynostosis. She had Chiari malformation, which means your brainstem is slipping down into your spinal cord. She had surgeries on her Achilles tendons so that she could move her feet. She has a rod in her right femur as that bone was starting to split through the middle. So those years are pretty jam-packed with all kinds of things. She's been pretty healthy these past few years, which has been really great. Gina: I'm happy to hear that. Yeah, that sounds like a really challenging time for you to navigate. What was that like? Did you find there to be a clear path to follow, or did you face a lot of surprises along the way? Lindsey: Yeah, I actually think most of it surprised us. We had a diagnosis and it changed. When we found out she had infantile hypophosphatasia with seizures, we also found out that all of the cases of kids with HPP and seizures had died by the time they were 18 months. So we were in a place where we had already had an incorrect diagnosis. We didn't really know what to think other than to take things day by day. Most of her early surgeries were emergent. They were things that needed to be done. They weren't really optional. If we wouldn't have fixed her skull, her brain pressure would've been too high. If we hadn't rodded her femur, it probably would've broken on its own. So we just lived those first several years, day by day, and doing the best we could with what we had. I mean, we didn't realize she was having seizures, at first, when she was little. Her arms would get stiff, she would stop breathing or she would stop breathing completely. She would have seizures if she got too hot and then too cold. So if we took her out of the bathtub and it was too cold in the bathroom, she would have a seizure. If we were outside and it was cold and brought her in and she got too hot, she'd have a seizure. The things that were really hard when she was little was that she couldn't tell us if she was in pain. So the first time she had craniosynostosis surgery, she was 10 months old. Well, her soft spot was starting to bulge. So we took her in thinking something was wrong. We didn't realize it was brain pressure because her skull was fusing. So I feel like those first few years were a lot of trying to figure out is she in pain? Is she hurting? Is she upset? What we needed to do and were we seeing the right specialists. It was a lot. It was when you're misdiagnosed with OI, what you're trained to do is how do you change a diaper without breaking their bones? How do you put a shirt on over their head if they don't have the neck strength to do that safely? So I think a lot of what we were doing when she was little was just praying that we would have the wisdom to know how to take care of her well, because there was so much unknown there that we really didn't know what to do. Her orthopedic surgeon would always say, "We're just kind of writing the book on this, so let us know." Then there would be times when we would take her into the emergency room for seizures and it was a type of seizure no one had seen before. There was one time when they called our neurologist and they were asking her questions, "Evie's here. We don't know what to do." And she said, "Well, you need to talk to her mom. Ask her mom what's going on." It was really wonderful for someone to say, this person is becoming an expert in this disease and her opinion and her perspective on this has value. So that was a big deal for me to know the things that we were seeing were going to sort of shape the future of what HPP looked like and how patients were treated. Gina: Love it. It sounds like you have become a real resource for the HPP community. And Evie, she has been a guiding light in so many ways. At less than 90 days old, she became one of the first patients to receive Strensiq, the first and only prescription medicine available for people with perinatal or infantile and juvenile onset HPP. It is truly amazing how far she has come since that time. But how did you feel when she first began the journey? Lindsey: Yeah, it was scary. I mean, we didn't know anyone who had been on an experimental drug trial. When you hear experimental drug, it's not necessarily your first hope, your first option, but we knew that if we didn't try it, she could become one of the other kids with HPP and seizures that had passed away. So we were really hopeful and grateful that there was a drug available that she could try, and we decided we'd do it to help her live and then have the best life she could. Gina: Evie, how has your diagnosis shaped who you are today? Evie: I'm short, but I feel like I have to work harder than other kids because my body works differently. It has also taught me that I'm strong and I can do anything I put my mind to. Gina: What does that look like on a day-to-day basis working harder than other kids? What is your day-to-day life like? Evie: Well, my feet hurt sometimes, and whenever I sit down, my legs get stiff and it's hard to get back up and stretched out, so I have to do PT so that I don't hurt all the time. Gina: Wow. That's quite a commitment. I think of you as such a brave person, being one of the first patients to receive this treatment. You really set the path forward for so many other little kids. How does that feel to you? Evie: I was a baby, so I don't really know. Gina: Good point. Evie: Now that I'm older, I hope that other kids see that their shots are helpful and that they can grow stronger, like I have. Gina: That's amazing. I'm sure you're helping all those parents of those little kids to feel better about it as well. So what is it like living with this disease? You told us about some of the pain you feel on a day-to-day basis. Are there other things about the disease you can share with us? Evie: It can be frustrating when I can't keep up with my friends and I don't get to play volleyball like my sister, which is kind of disappointing. Sometimes I can't do stuff that my friends can do, which is also disappointing. But I can also do things like hunting and other sports. I have a hunting bow, and I tried hunting this first fall, and so it went pretty well. I just love being out in nature, even though I didn't get anything. Todd: In addition to stunted growth, HPP patients like Evie often face mobility limitations. These might include keeping pace with friends, standing comfortably for long periods or standing from the sitting position. For Evie, her short stature made volleyball a bit of a challenge, but she really found her stride in archery. Given her dedication to physical therapy, Evie has developed significant upper body strength, which allowed her to handily manage her first bow, a gift for her 10th birthday. She outgrew that bow within a year and has gone on to master both target bows and hunting bows in archery competitions with her peers. Let's hear more from Lindsey on how Evie's treatment journey led to where she is today. Gina: So Lindsey, how has Evie progressed since receiving her first dose of Strensiq? Was the progress immediate? Has it been slow over time? What does that look like? Lindsey: Yeah, she started Strensiq when she was three months old, so we really don't know what life would be like without it for her. Our first goal was just to get her off of oxygen. So she started the treatment and within a month, she was on supplemental oxygen because we just couldn't keep her saturations high enough. That took about two years. It just took time for her ribs to strengthen, to support her lungs. And then in the meantime, we were watching her bones get stronger and harder as she had X-rays all the time to make sure that Strensiq was going in the places it should and not in the places it shouldn't. It was pretty fantastic to watch her bones go from mostly cartilage to bone and get long and straight, and it was great. Gina: How often is the treatment required now? Evie: I used to get three times a week, but now I get six days a week. Gina: And how are those shots administered? Evie: Yeah, so well, my dad was, at first, giving them to me in my arms and legs, and then I tried it once when I was nine or 10. I could do it in my legs, and then I tried it one time in my arm, and that was really successful. Todd: As many rare disease families will tell you, it can be hard to find resources in your search for treatment. Prior to the advent of the internet and social media, this search was next to impossible. But today, more and more connections are being made between rare disease families. Lindsey shared with us that in her online research, she was able to connect with the mother of Strensiq patient number one, who called her all the way from Ireland to share her experience with the treatment. Since then, Lindsey and other HPP families have shared their knowledge through online forums and advocacy organizations like Soft Bones. Soft Bones, a Charles River partner, raises awareness about HPP by advocating for research, funding grants and connecting patients with each other and members of the medical community to advance understanding of the disease. A large part of their mission, as seen on their website, is educating the public about early warning signs of HPP. Let's hear from Lindsey on why this is so critical. Gina: You shared details about Evie's diagnosis, but despite all of that awareness and effort, is early diagnosis an issue with HPP or is that pretty much gone away now? Lindsey: I think it used to be. When Evie was diagnosed, we heard from so many people how lucky we were that she was diagnosed accurately because back then, a lot of people were misdiagnosed with OI or people with less severe forms, it takes a really long time to get diagnosed. It can be misdiagnosed as lots of things or even just missed altogether. So it was a really big deal, especially for us because according to our doctor, her bones probably would've deteriorated without the alkaline phosphatase that they needed to get stronger. So having that was huge for us. Gina: Wow. One of our previous episodes of Vital Science, we touched on access to treatment and sometimes the high cost of that can really be a deterrent for patients. Do you have a point of view on that and how we can make therapies accessible to patients? Lindsey: Yeah, I really think that patients need rare disease advocates who can walk them through the steps of diagnosis and treatment options. I wasn't working when Evie was little and her healthcare was pretty much a full-time job. We had a two year old, her older sister, and her and I would make phone calls to insurance companies, write appeal letters, schedule doctor's appointments, contact specialists. It really took most of my time. There was a period of time when she was in the hospital for a month and we ended up just actually moving into a hotel that was connected to the hospital. My husband worked there, so he would go to work and then I would go be with Evie all day. He would go spend the night in her room. I would spend the night in her room. So I think it's just really important that companies who are making the cost of these drugs, who are helping patients get access, realize the impact that it has just outside of the shock of a rare disease diagnosis. Todd: A common theme of discussion on Vital Science is the positive impacts of collaboration in the drug development process. Our conversation with Lindsey and Evie amplified a voice in this collaboration that we have not heard much on the show, and that's the voice of patients and their families. While it is now common for clinics focused on oncology and diabetes to have patient coordinators, when it comes to infantile and juvenile rare disease, this role often falls to the patient's parents. So just as pharmaceutical organizations consult medical staff to understand patient's clinical challenges, so too should they seek the input of rare disease patients and their families as they invest in this area of vital research. For Lindsey, a seat at this table was found through Soft Bones, which has served as a critical link between patients and drug developers. Pharmaceutical companies now attend Soft Bones national patient meetings where they're able to ask real HPP patients and their families about their experience with treatment, if six days a week feels like too many doses, where they store their medicine, if injections hurt more in their arms or their legs. These important insights are taken back to the scientists in the labs to help further improve treatment. Let's hear from Lindsey on how Evie and other HPP patients have benefited from Strensiq. Gina: When you think about Strensiq and the fact that it has worked so well, that it really does what it sets out to do and is so effective, how do you think that the success of that drug development translates to other children diagnosed with either HPP or even other diseases around the world? Lindsey: Yeah, Strensiq has probably saved Evie's life. It was a huge deal with early diagnosis. It took a couple months for her to get approved to be on the clinical trial, but the fact that she could receive the drug before her bones got worse and that she could impair her lung function, that her ribs could grow, it was a game changer for us. I know there's kids in other countries that don't have access to Strensiq because of government or insurance issues, and it's a big deal. It's a really big deal that especially while kids are young and they're growing, they have access to the things that they need. Gina: I think part of the progress that we're seeing that I hope also leads to greater access is the collaboration that companies, organizations, academic institutions, industry, as well as companies like ourselves, contract research organizations, are collaborating more and more starting earlier on the therapies and focusing on those tough to diagnose conditions. In your opinion, why are these collaborations important? Or do you see any benefit personally from any of that work? Lindsey: Yeah, one of the big things that I've seen since the beginning was when she started on the clinical trial, she was patient 10-1. Every paper we would fill out had her listed as patient 10-1, and we didn't know anyone in the pharmaceutical industry, outside of our close network of doctors that was treating her. And now I feel like we see people from Alexion and they know her name. We see people from Charles River, and they know her name. So I think the collaboration has been huge. I think it's turned her from a number into a person, and I think that that is what really moves people to want to work hard to find drugs that save people's lives. Gina: Yeah, that's really true, very true. I think that all the people that work at Charles River know Evie's name and know her story. You're very motivational to all of us, Evie. Just thinking more along the lines of that collaboration, I mean, it's our hope that it helps to make drug development faster, to really expedite it. I don't know if you've seen that or felt that, but it is our hope that that's what comes of the collaboration. Lindsey: Yeah. I think that really early on, what we saw was there was a doctor who had years of experience researching alkaline phosphatase. There was another doctor who had years of research on HPP and then a small drug company that was willing to try to make a drug trial. Even just seeing those three pieces come together, we actually have gotten to meet all of those people and it was really huge to see someone cared enough to research this and put their research together with someone else to make a drug that worked. Seeing that on a larger scale, I think now with companies like Charles River, has been really encouraging because you will get to make drugs for diseases and people need access. Soft Bones organization has worked so hard to make information available for patients, families, doctors, industry, companies. A lot of the connections that we have have been through the Soft Bones organization. When new patients come in whose babies are diagnosed, a lot of times I'm tagged in a post to connect someone or sent a message that that mom might need help. They do fundraisers, they award grants, they're in contact with researchers. So it's been a huge deal that they're working hard I think that companies are listening. I think that companies like Charles River are listening. I think that you guys are helping us get out information about HPP and the more people that know about it, the more support that we can get, the better Evie's life will be and other people who have HPP. Gina: Yeah, what a wonderful organization. Thank you for sharing all of that information. So Evie, you seem to be doing really well. We're all very proud and happy for you here. Seventh grade, what's next for you on your journey, whether it's things you like to do or what you see for yourself? Evie: Next year, I'll be in eighth grade and then I'll be in high school. Gina: Yeah, that'll be a big experience. When you think back to... You're almost, I mean, you are famous to me anyway, what do you think about your legacy? What do you think people will say about you or what do you want to be known for? Evie: I want people to know they can do hard things and get through their struggles. Gina: Yeah. Thank you for that. Is there anything that you want listeners to know about you? We have a big audience and love to hear anything about yourself that you want to share. Evie: I want to help others overcome their fears of shots. I know that it is worth it. Gina: Yeah, especially as a visiting nurse, I'm sure you'll make a lot of headway there. Lindsey, is there anything else you want to add? Lindsey: Yeah, I would just tell people who've maybe been diagnosed with a rare disease or on that journey, it's hard and it's also been so worth it. I've got to watch Evie succeed in things we never thought she'd get to do. I get to watch her enjoy time with her friends, and yeah, I'd do it all again if I had to and yeah, I'm just so thankful that we get to have her. Gina: We are too. Thank you both so much. It was wonderful having you on the podcast, seeing you again and hearing about what you've been up to, Evie. So thanks, so much. Evie: Thank you. Lindsey: Thank you. Todd: You can learn more about Evie's incredible journey at criver.com/everystep. For more information about hypophosphatasia, be sure to visit the Soft Bones website at softbones.org. Looking ahead to our next episode of Vital Science in April, we'll talk with founder and CEO of the n-Lorem Foundation, Stanley Crooke, about his organization's mission to deliver ultra-rare disease treatment one patient at a time. Until then, thanks for listening.