I AM BIO

How Love Combined with Science Leads to Hope for Rare Disease

Episode Summary

There are over 7000 rare diseases identified in the U.S. alone. Many of these diseases affect children, leaving families desperate for answers. In this episode, we talk with one of those families and the biotech company offering them new hope. We also talk with an expert on policy that has jump-started R&D for rare diseases.

Episode Notes

There are over 7000 rare diseases identified in the U.S. alone. Many of these diseases affect children, leaving families desperate for answers. In this episode, we talk with one of those families and the biotech company offering them new hope. We also talk with an expert on policy that has jump-started R&D for rare diseases.

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Episode Transcription

Theresa Brady (00:33):

Rare diseases are just that, rare. Yet with over 7,000 of them identified in the U.S. alone, the chance of having a rare disease isn't as uncommon as it might seem. Many of these diseases affect children, leaving families desperate for answers and often finding themselves without adequate support or advocates. In response, they take matters into their own hands, becoming powerful drivers on the road to potential cures and treatments.

(01:03):

Today we talk with one of those families and discover how love and determination can power the surge for finding treatments. I'm Theresa Brady and you're listening to I am BIO.

(01:33):

Over the past 40 years, numerous patient groups have emerged to raise awareness and advance research for rare diseases. Thanks to their efforts, these once overlooked conditions are now part of global health care agendas. As many of these families are in a race against time, they are joining forces with biotech companies and policymakers to accelerate the development of treatments.

(01:58):

Today our guests are from different parts of this critical partnership. We talk with a family facing a frightening diagnosis, a biotech startup working on a breakthrough treatment, and an advocate fighting for policies that incentivize research and development in rare diseases. First, let's meet the Dions.

Courtney Dion (02:19):

Hi, my name is Courtney Dion. I am the President and Cofounder of Dion Foundation for Children with Rare Disease.

Joe Dion (02:26):

Hi. My name is Joe Dion, Cofounder, Treasurer of the Dion Foundation.

Theresa Brady (02:31):

In 2022, the Dions and their three kids were enjoying the summer when they noticed something different about one of their children.

Courtney Dion (02:38):

So, looking back at the summer of 2022, our son Peter, our oldest, was nine at the time. We were spending a lot of time on the boat. Our summer vacation, we take the boat for a week and we travel around New England. We really noticed that Peter was having a tough time climbing ladders and getting on and off the boat, and climbing, and keeping up with his siblings, and that was kind of the moment that I realized something could be wrong, that he was regressing, n- not being able to do things that he had done the previous year.

(03:16):

Just from my background knowledge as a nurse, I kind of had this realization that some childhood muscular dystrophies have an onset in mid-childhood. So I had this overwhelming sense that I needed to get him checked out. I brought him to our PCP for labs. She agreed and he was found to have a sky-high CK which indicates muscle damage. So then we were referred to a neurologist, and obtained some genetic testing. His DMD panel was negative, so then we went on for further testing and genetic testing revealed a form of limb-girdle muscular dystrophy.

(03:56):

So his rare disease is limb-girdle muscular dystrophy type 2C.

Theresa Brady (04:01):

Limb-girdle muscular dystrophy or LGMD is a genetic disorder that weakens muscles around the hips and shoulders. In the Dion's case, each parent had passed on the mutated gene to their son Peter, and unlike other forms of muscular dystrophy that primarily affect one gender, LGMD can affect both males and females.

Courtney Dion (04:22):

We learned that that was an autosomal recessive disorder, which can affect both male and female. We were looking at both children, you know, knowing that one gene comes from the mom, one gene comes from the dad, looking at our other children. Maggie, who was six at the time, was exhibiting some of the early symptoms that we didn't realize with Peter when he was six. So her early symptoms were toe walking. So we had the feeling that we needed to get her screened as well. We had her genetic testing sent off, and it came back with the same genetic mutations, which means she has the same disorder as her brother.

Theresa Brady (05:00):

Courtney describes the pain of watching her children endure this debilitating disease and why time is not on their side.

Courtney Dion (05:08):

My 11-year-old son Peter, he is progressing through his illness. When he was diagnosed he was nine, and was having trouble climbing things. Now he's 11 and stairs are a real challenge. When he falls, now he can't get up off the ground without help. He has to take extra time at school and he just started middle school, so it's tough. You know, he's going into this whole new school, kids are saying, "What's the matter with you?" and it's hard for him because he's a hundred percent cognitively aware of everything.

(05:42):

He's thriving every other aspect of his life. He thrives in school, he thrives in his social groups, he's happy, but for him to just sit there and watch his body fail him daily and losing independence. Rather than at this preteen age he should be gaining more and more independence, he's losing independence. Um, so that's really tough to watch, and that kind of is our driving force. You know, we have an hourglass tipped up and we have sand falling down and we don't have a lot of time to make a difference to kinda halt his disease process or even help him in this disease process.

(06:21):

So that's our driving force, t- is to get these kids some help to help preserve some of their function, preserve some of their independence, live somewhat normal life, enjoy their lives. That's our goal.

Theresa Brady (06:35):

The Dions describe their initial struggles coping with the news and figuring out what to do next. Here's Joe.

Joe Dion (06:42):

The diagnostic journey for us, it seemed like forever, but it was actually pretty quick when we look back and as we learnt more about what families go through during these times. We're in a day and age where genetic testing is pretty readily available if you go to look for it. So it seemed like eternity, which was like two months of going through the different panels and checking for Duchenne muscular dystrophy, and then that came back negative, and then looking at the limb-girdle panel. In hindsight we were real lucky that it, that it was quick, meaning it was two months. We have met families that took them decades to get diagnosed.

(07:20):

So overall we're thankful for the folks before us that advocated and pushed for genetic testing and made it free. I would say thanks to MDA and the other larger groups that have fought over the years, our diagnostic journey was pretty quick.

Theresa Brady (07:35):

Once they had the diagnosis, the Dions began in earnest to find out more.

Joe Dion (07:40):

The internet is a vast wealth of knowledge. So w- we were lucky that we could Google it. We talked to families in the past that were even diagnosed 10 years ago, when they got diagnosed, nothing came up on a Google search. We were lucky but also unlucky at the same time to find that there was nothing, there was no treatment. Our neurologist in Boston at the time said basically, "There's nothing we ca- we can do. We'll see you in six months for a multi-clinic," where they check the heart and lungs and stuff like that."

Theresa Brady (08:10):

Parents are rarely willing to accept, "There is nothing we can do," and Courtney and Joe are no exception. Courtney is a nurse, which helped her understand and jumpstart the research.

Courtney Dion (08:21):

I would say having a basic nursing background has kind of set me just a step ahead. You know, I never knew that I would be dealing with rare diseases and gene therapy, and, you know mouse model studies and reading all about antibodies and all that.

(08:37):

So it has given me a, a little bit of an extra step ahead, just to be able to understand what I'm hearing from the doctors, understand some of the research studies that I'm reading, and also, the biggest kinda takeaway from my nursing career is that advocacy piece. As a nurse you advocate for patients all day long. You're advocating for their best interest, for their wellbeing, and now I'm in my greatest role doing that, advocating for what my children need, which treatments their gonna need, what's gonna benefit them, what's going to benefit all kids with 2C.

Theresa Brady (09:09):

And Courtney and Joe are determined to fight for their kids.

Courtney Dion (09:13):

Joe and I's driving mission is that, you know, if s-... no one is gonna do this for us, s- nothing is gonna come knocking our door, we have to kind of go fight for our kids and make our needs known and there's other kids out there who are, who are waiting, who are sitting and waiting, and they might not have the platform that we have been able to find, or they might not have the chances to be able to explain how dire this need is, and that there are children waiting.

Theresa Brady (09:42):

In 2023, the Dions poured their fight and energy into founding the Dion Foundation for Children with Rare Disease. The foundation's mission is to raise awareness, and also fund research and development for limb-girdle muscular dystrophy.

(09:57):

Courtney says it's important for the foundation to be a resource for other families facing the same diagnosis.

Courtney Dion (10:04):

Number one, we wanna be a resource. We spent no time after our diagnosis before we dove into learning and educating ourselves, finding the medical professionals throughout the country who are specialists in this area. We have been to multiple conferences. We have met some of the leaders in this space, who have been working on these genetic disorders for 30, 40 years. We've spoken with them, we've learned from them.

(10:35):

So with all of that effort, that's our number one thing, is to be able to share that with families, if someone were to come to us, which they do. We have people reaching out from the UAE, we have people reaching out from Africa, from Italy, with new diagnoses. So number one, we wanna just share what we have learned and kind of cut that two years of education and hand it to them on a sheet, and that saves them time, that saves energy in trying to find all that information on their own.

(11:08):

Secondly, we want to encourage these families and parents mostly, because parents are getting diagnosed when their kids are in their mid-childhood. We want to encourage these parents to get involved as much as they can join us in advocating for the needs for these children. The more people making noise and the more people who are expressing these urgent dire needs, then that's what we need. That's how we make a voice and that's how we're gonna make a change.

Theresa Brady (11:38):

Joe agrees that every success or milestone reached builds on what has come before it.

Joe Dion (11:43):

We're really lucky with the work that happen in, uh, Duchenne muscular dystrophy, so we can use that as a pathway. We look at, in gene therapy, each one of these subtypes need a different clinical trial. Now you can look at them as a platform, which is like, you know, one company can essentially use the same vector and the same transgene and put in a different gene for each one of these subtypes, but each one of them i-, you know, it's a different drug to market as far as the FDA is concerned. So we need multiple shots on goal for our disease.

Theresa Brady (12:18):

As a parent myself, I can't imagine going through something like this, but as Joe says, they never lose hope.

Joe Dion (12:24):

We stay really motivated and optimistic about what's going on with limb-girdle muscular dystrophy type 2C, and the reason is is because we haven't been shut down yet. As parents and patient advocates we've been able to get meetings, we've been able to talk to who we need to talk to, and that's 'cause we're perseverate and we're making the call and we're shaking the tree, trying to get that meeting with the next person in line.

(12:52):

So it's frustrating, but if I could just add, you gotta fight. That's hands down what you need to do every day if you want anything done. With the hard work between everyone on our team, we've really been able to get a lot done.

Theresa Brady (13:08):

Including finding a company working on a gene therapy for limb-girdle.

Joe Dion (13:12):

We learnt about them from the internet. We're lucky that... I kinda touched on this earlier, but if this was 15 years ago, nothing would even show up. So due to the technology and Google basically, we're able to find these companies and see who has any science and when you're looking at an ultra-rare disease like limb-girdle, it's pretty easy to find 'cause there's not a whole lot.

(13:35):

That's how I found them, and the relationship has been great so far. They need support. They need people that are gonna help them move this along. They definitely have a forward-thinking mission that aligns with ours, so it makes sense for us to collaborate with this trial and we can give them the financial support to keep the ball moving here in United States through the public charity.

Theresa Brady (14:01):

The company the Dions discovered is called Atamyo. Our next guest is their CEO.

Stephane Degove (14:07):

Hi. My name is Stephane Degove. I'm the CEO of a biotech company called Atamyo Therapeutics.

Theresa Brady (14:13):

Located in France, Atamyo is a gene therapy company focused on neuromuscular disorders like limb-girdle muscular dystrophy.

Stephane Degove (14:22):

Our mission is to bring to patients suffering from severe neuromuscular disorders life-changing treatments. More specifically, we do gene replacement using a new generation of AVs and we target two family of diseases. The first one is called limb-girdle muscular dystrophies, LGMDs, and we also target cardiomyopathies.

Theresa Brady (14:46):

Stephane explains how the partnership between the Dion Foundation and his company came about.

Stephane Degove (14:51):

Yeah, so I taught MIU. We did a lot for gene therapy for, uh, LGMD called LGMD type 2C/R5, caused by the mutation of a gene [inaudible 00:15:00] for protein gamma-sarco.

(15:06):

We did a press release earlier this year announcing that we had the clearance to start a clinical trial in Europe and that's how we were contacted, uh, by, uh, the Dion Foundation.

(15:17):

This foundation is focused on this disease, uh, which affects children in their young age, and, uh, as most of these children are losing the ability to walk before the age of 15, time matters. Uh, it's really a countdown for this patient to have access to treatments.

(15:34):

So they contacted us first to see how we could have U.S. patients traveling to Europe to benefit from this experimental treatment, this clinical trial. Very quickly we found it would be a better idea to, to work together, to expand into the U.S. the clinical trial and, uh, open a U.S. center.

Theresa Brady (15:54):

The two partners quickly got to work and last month Atamyo made an exciting announcement.

Stephane Degove (16:00):

So, indeed as we announced on September 30 we have find a, an IMD for this program, and we, um, in order to, to start enrolling patients before the end of this year and we are working closing with a leading U.S. center in gene therapy for, uh, these rare pediatric diseases.

Theresa Brady (16:18):

This is undoubtedly great news for the Dion family, and as Stephane explains, if Atamyo is successful, some of the credit will go to the Dion Foundation.

Stephane Degove (16:28):

So the Dion Foundation is helping us a lot to, to facilitate the U.S. expansion by first providing financial support. Expanding in the clinical trial in the U.S. costs money. And second, they also are very helpful in connecting us with the U.S. uh, clinical trial center with who, uh, we will work.

(16:46):

The Dion Foundation, uh, has identified the first patients that will be screened, uh, for this trial, and, uh, I know that there are fully committed to identify more patients. So it's a key value added to this program, and, uh, a big help to have these U.S. patients benefit from this, uh, treatment.

Theresa Brady (17:08):

The treatment the company is testing is called ATA-200, a gene therapy that targets the faulty gene responsible for LGMD2C. It is a one-time treatment delivered intravenously using a harmless virus known as Adeno-associated virus factor, AAV. The AAV helps carry the healthy gene into the patient's muscle cells. This is how it works.

Stephane Degove (17:33):

ATA-200 is a gene replacement through AV, so we insert the gene in another new virus that is specifically designed to having this protein expressed in skeletal muscles and in the heart.

(17:46):

So ATA-200 replaces the mutated gene, uh, by a functioning gene, uh, in the, uh, affect muscles. Therefore, the muscle will start to produce again a functioning protein, the functioning, uh, gamma-sarcoglycan protein.

(18:02):

In preclinical models done in mice, uh, carrying the same mutation as patients, with a single, uh, administration of ATA-200 we were to fully restore the force of these mice and, uh, [inaudible 00:18:17] of their muscles.

(18:18):

And in addition, we have introduced in this, uh, ATA-200, uh, vector, a promoter that, uh, prevents, uh, liver and cardiac toxicity, so in preclinical, uh, development we have shown what is called a very good safety margin, very few, uh, adverse events with our treatments.

(18:36):

In, in preclinical models we have seen a reversal of the disease and we hope now to be able to document these reversal properties in patients.

Theresa Brady (18:47):

For the Dion family, this treatment represents more than just medical advancement. It offers the possibility of a better quality of life for their children.

(18:58):

Both Stephane and the Dions talked to us about an important government program that has helped bring numerous rare disease treatments into existence. The program, administered by the FDA, is called the Rare Pediatric Disease Designation and Priority Review Voucher Program or PRV for short.

(19:18):

First established in 2012, the program is designed to accelerate access to life-saving and life-improving treatments for patients who desperately need them. Our next guest is a advocate for patients affected by rare diseases and an expert on the benefits of the PRV program.

Jamie Sullivan (19:36):

I'm Jamie Sullivan. I'm the Vice President of policy for the EveryLife Foundation for Rare Diseases.

Theresa Brady (19:41):

Jamie gives us some background on the EveryLife Foundation.

Jamie Sullivan (19:45):

EveryLife Foundation is a nonprofit, nonpartisan organization. We are a patient organization. We are dedicated to empowering the rare disease patient community, to advocate for impactful science driven legislation and policy that advances equitable development of and access to, importantly... um, (laughs) access to life-saving diagnosis, treatment, and cures. Ninety-five percent of rare diseases still have no FDA approved therapy specifically for that disease.

Theresa Brady (20:15):

To improve the chances of reducing this unfortunately statistic, EveryLife Foundation engages in a number of initiatives aimed at making rare disease a public health priority. One of those initiatives is to make the PRV program permanent. In its current form, the program must be reauthorized by Congress every few years, which creates a lot of uncertainty for the program and its users.

(20:40):

In a nutshell, the PRV program allows a company that successfully develops a medicine for a rare pediatric disease to receive a voucher. With that voucher in hand, the company is afforded a reduced timeline for approval of their next product or they can sell the voucher to another drug developer.

(21:01):

Jamie explains that this market-based incentive does not cost the taxpayer anything and is a win-win for rare disease.

Jamie Sullivan (21:09):

That voucher can then be used by that company on a future new drug or biologic application to obtain priority review if that drug did not otherwise qualify for priority review or it can be sold or transferred to another company, which in many cases in rare that's what happens because that is the incentive. The ability to sell the voucher, to raise that capital, to then reinvest back into their development programs, whether that be reinvesting in additional research on the drug that was just approved or starting up new rare disease programs or having to invest in, in being able to bring that rare pediatric drug to the market. Especially as more therapies are more complex and innovative and complicated to manufacture, the money they get from selling that voucher is the incentive. It is part of the calculus that companies will consider when deciding whether or not to get into and invest in a new rare pediatric condition.

(22:13):

And so it's a really important piece of the toolbox of what incentivizes investment in rare disease research.

Theresa Brady (22:21):

Companies buying the vouchers may not be working on rare pediatric diseases, but Jamie says it's a trade-off they're willing to accept.

Jamie Sullivan (22:29):

Sometimes we'll hear well, vouchers mean that drugs that aren't public health priorities get put to the front of the line. We accept that trade-off. The, the company using that voucher, yes, a treatment that wouldn't otherwise qualify for priority review gets priority review, but what that means is that another disease that treats kids might have a treatment because of it. That's an okay trade-off to make and it's something that we have to, we have to have ongoing. We can't lose a tool, one of the few tools we have to make sure that investment continues, that we capitalize on the promising science of today and translate that into treatments in the near future, not for generations down the road, but now.

(23:13):

We do know that the Peer Review program is working. It's led to the approval of at least 54 new rare pediatric treatments and those are spread out across 40 rare disease communities and some oncology communities as well, and those are real people.

Theresa Brady (23:31):

As it stands right now, the PRV program will begin to sunset after December 20th of this year, and the FDA will not be able to award any vouchers after September 30th of 2026. Jamie says that if the program isn't reauthorized it will be tragic for the rare disease community.

Jamie Sullivan (23:50):

If we lose that option, if we lose the PRV because Congress doesn't extend the program, it's really tragedy for the rare ecosystem because it s- doesn't cost the taxpayers money. The value of the PRV is what the market determines and so it's a no-brainer in many people's minds (laughs), but yet it's something that we have to keep fighting for every few years, and as you know when you're fighting just to keep what you have, it's really hard to make progress on other things because it takes so much energy and so much bandwidth to just keep what we have, instead of being able to redirect all that energy at looking at what do we need to do to move forward?

Theresa Brady (24:32):

It's interesting that most people, especially those in Congress, agree that the PRV program makes sense. So why does it take so much effort to continue it?

Jamie Sullivan (24:41):

There is fairly broad bipartisan support, but there's also a lack of urgency. And so when we're in a time where very little moves through Congress as standalone legislation, especially in the Senate, we need that urgency to make sure that programs are extended on time, that they get on the radar of the committees that need to mark them up and put them through regular order, that we have that champion that can make sure whoever is setting agendas is truly understanding this has to be on it, this is critical, this isn't a nice-to-have. And it has been reauthorized multiple times. We are hopeful, but we can't take anything for granted. So we have to work extra hard and we have to engage advocates and evidence and all of it has to be focused on making sure we get this across the finish line.

Theresa Brady (25:34):

For the sake of the Dions and every family facing a rare disease diagnosis, we hope that the PRV program continues for as long as it's needed.

(25:51):

I wanna thank our guests, the Dions, for sharing their deeply moving story and Stephane for his company's dedication to providing meaningful treatments.

(26:00):

A special thanks to Jamie and EveryLife Foundation for their ongoing efforts to advance policies that ensure that no disease is too rare to deserve treatment.

(26:11):

If you like what you heard today, be sure to let us know with a review and remember to follow us on X, Facebook and Instagram @iambiotech. We're also on LinkedIn @biotechnologyinnovationorganization. I'm Theresa Brady and I produced this episode with help from Kourtney Gastinell. It was engineered and mixed by J. Goodman with theme music created by Luke Smith and Sam Brady.