Hey FDA! Our galactosemia community is small but resilient (and loud) - and we deserve a treatment!

The day Francesca was diagnosed with galactosemia - a disease we had never heard of and could barely pronounce - we knew the possible long-term complications. But unlike many of our friends in the galactosemia community, the galacto girls were largely unaffected. No speech delays, no apraxia, no fine motor skill issues, tremors or seizures. Yet. But we knew the reality. They would likely somehow be impacted. We just didn't know when, or how severely. We would leave each specialist appointment with glowing reports of no concerns, but also with words of caution that many of the delays don't show up until elementary school age. That's when the math and reading challenges will be more noticeable. And then of course we heard the stories of Primary Ovarian Insufficiency (POI) that will likely make having families difficult, if not impossible for them. 

Still largely unaffected - when a clinical trial started for the first ever possible treatment of galactosemia

- we didn't immediately get involved. But when you're a rare disease - every participant makes a difference. So when they announced a clinical trial site was opening up 45 minutes away for us, we enrolled Francesca (actually we enrolled both galacto girls, but because of Amelia's small size and low BMI she wasn't eligible to participate.) So we enrolled in the clinical trial for what we thought would be a year - until Applied Therapeutics could provide data showing a reduction of galactitol in the study participants while proving the drug was safe. 

Read about the start of the clinical trial:

https://galactosemiagirl.blogspot.com/2021/07/the-galacto-girls-join-clinical-trial.html

https://galactosemiagirl.blogspot.com/2021/07/francesca-starts-clinical-trial.html

During the clinical trial there was a change in leadership in the rare disease division of the FDA. And with new leaders, come new rules. The accelerated approval option Applied Therapeutics was told they would likely have was taken off the table. Suddenly, showing the galactitol reduction wasn't enough. And our hopes of a treatment slowly started to fade. You see, getting a drug through a clinical trial and approved to market can take years. Ultimately you need to prove the drug is safe and it works. But that gets a lot more complicated when a rare disease is involved. First, you don't have a big candidate pool to recruit from for the trial, then some who want to participate aren't eligible (like in Amelia's case) and you add in having some of the study participants on placebo...it makes proving the drug works (by reaching statistical significance as determined by the FDA) extremely difficult. 

About a year ago, when what Applied Therapeutics would have to prove and deliver changed, the Galactosemia Foundation rallied our community, upped our advocacy game and made sure the FDA knew why we needed a treatment. We understood that while there wasn't yet enough data to show this medicine would work, we knew it was safe. And we knew it was reducing galactitol. And that was enough. We knew it was better for our kids to be receiving it, while data was gathered to prove that it worked, then wait until statistical significance was reached. So we wrote letters to the FDA, we contacted our legislatures via email and left voicemails. We got automated and short replies back from the FDA - we were told we had been heard. But that was it. And we saw no movement from it. 

Read my blog from last year about our advocacy efforts:
https://galactosemiagirl.blogspot.com/2022/02/the-clinical-trial-fda-congress-and.html

Earlier this week Applied Therapeutics announced its 18 month data. The evidence is compelling - there were notable gains made in the kids who were on drug - but it fell just short of being statistically significant. 

According to Applied Therapeutics data showed the Govorestat treatment improved life skills, behavior, cognition, fine motor skills, adaptive skills and tremor vs. placebo. The one place statistical significance was not seen (put had positive trending) was speech. While we don't know for sure, it could possibly be because speech therapy is an existing effective treatment and many kids are already receiving this treatment (including those on placebo). So when they combined all the data at the end (with three out of four criteria meeting the statistical significance.) The final number fell short and did not meet statistical significance. 

And while I understand the need to have a number to reach, something to measure success by - not everything is about the numbers. While the FDA might not have found the results statistically significant, ask the mom who has seen a reduction of tremors in her child since starting the clinical trial, ask the dad whose child can remember and comprehend things better, who is making friends easier and regulating better. Families are seeing positive changes since being in the clinical trial. And the thought of this drug not getting approved because it fell just short of the required statistical significance when families have real life evidence that it is working and is safe, is heartbreaking. Numbers are important. They aren't everything. And we need the FDA to know that the evidence is compelling and it matters and we need them to approve the drug as soon as possible. I'll make a quick side note here - the study hasn't been unblinded yet - so as I write this, we are assuming the families who are seeing improvements are on drug. As for us, I am about 99% sure Francesca is on a placebo, which is important to know for the next part.

And then there is our story. . Earlier this week, I sat in a room next to my husband and surrounded by a
group of educators trying to figure out how to best keep Francesca from falling even further behind in math and reading. We knew last year she was a little behind, but it was hard to know if it was a complication from her galactosemia or the result of the pandemic and the online school, etc. But this year she continued to fall behind her peers. Thankfully there was a tutoring opportunity available and she's been receiving reading and math tutoring two days a week for the last few month. And while we are seeing some improvement in reading - she isn't making progress in math. My standard joke of "she has two journalism major parents, she'll need a math tutor anyway" isn't funny anymore. She is struggling. And as I sat around the table with her principal, a psychologist, a social worker, her teacher and another support staff member I realized how lucky we are to be in a school district that is proactive and set up to help struggling kids. I have a feeling not everyone is that lucky. This wasn't a meeting I requested. Her teacher saw a struggling kid and did everything she could to make this meeting happen. She even said in the meeting that it is heartbreaking to see how hard Francesca tries. And always with a smile and a great attitude. But she's just not retaining the information. She's not making progress. And I heard the words from a fellow galacto mom in my head "Jodie, she needs to get on the drug...I feel like you would see big changes." And my eyes filled up with tears. I have a kid who is struggling and many resources to help her - but they aren't working. And there is a drug that is proving successful for many families. But it may not get approved because it didn't reach statistical significance in 1 area. 

So what's next? The study should be unblinded soon and if Francesca was on placebo we will be able to switch her to active drug. We will need to make a trip to Ann Arbor for this and then she'll have monitoring (blood draws) for a while after she starts. There are some known rare side effects so she will be monitored for the first few months to make sure she doesn't experience them. 

Applied Therapeutics will be requesting a meeting with the FDA in the next 30 days to discuss the results and why the drug should be approved. In the meantime, the Galactosemia Foundation is setting up a communications push to rally our community, family and friends to help us communicate the need for a drug and urge the FDA to carefully consider galactosemia patient and caregiver experiences during their review of this potential treatment. The numbers are compelling but the real life stories are more important. Every day our kids don't have a treatment is another day damage is being done to their bodies. We need the FDA to see it from our perspective. The data might not seem significant to them, but it has been life-changing to some of the families who are participating in the clinical trial. We need these kids to continue to receive this medicine. And we need it available to all those living with galactosemia. 

In the coming days and weeks the Galactosemia Foundation will be creating resources and putting them on our website to help our community, family and friends come alongside us in advocating for the approval of the medicine. I'll be posting on our Adventures of Galacto Girls Facebook page when these items are available with specific ways you can help. 

Here is the Galactosemia Foundation press release calling for the FDA to take the patient voice into account.

Here is an article our VP Brittany Cudzilo was part of talking about the challenges we're facing.