Angelina's Miracle

This is our daughter, Angelina. After a completely normal pregnancy and birth, she turned our entire world upside down when she started having seizures at just a few months old. Dozens of tests and scans revealed nothing until a genetic panel came back with a diagnosis, STXBP1 Encephalopathy (see https://www.stxbp1disorders.org/what-is-stxbp1). She had a small mutation in a gene that made a critical brain protein, and because of it, she would have seizures, severe learning and intellectual disability, and movement disorders with no effective treatment except for muscle relaxants and antiseizure medications. These would only treat some of the symptoms, however, and even then, most of the children with her condition will still be plagued with seizures, and the hopes of her ever walking or talking are slim. While her seizures have been well controlled with Clobazam, a benzodiazepine like Xanax or Valium, the side effects have been awful; drowsiness, poor coordination, poor vision, weak swallow and feeding difficulties, just to name a few.

Hope came from Cornell University, as researchers discovered a few molecules that were able to go into the brain cells and help fix the problem with the STXBP1 protein. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162227/) Even more exciting is one of them was an FDA-approved medication for Urea Cycle Disorders called Ravicti (glycerol phenylbutyrate). A trial was organized that started in 2021 for 10 children with Angelina's condition to try the medication for a month and have the option to continue it for up to a year. Angelina, however, did not qualify, as her seizures were controlled, and reduction of seizures was an endpoint for the study to measure the medication's effectiveness. Being a medication already on the market, nothing stops a doctor from writing a prescription off-label; it's just that at $6,000+ per 25ml bottle, few parents would be able to afford 3-11 bottles per month.

Fast forward to this year, Angelina started having seizures again. Our neurologist recommended increasing her dose of Clobazam, as we had been on the same dose for over a year. We did so, and while it reduced the number of seizures we were seeing, it also caused her to regress severely. Not quite crawling, but turning over and getting up onto hands and knees was something she would do on her own 20-30 times a day before increasing the dose. After increasing the dose, that went down to 1-2 times a day, if at all. It wasn't acceptable to us to drug her up with sedatives, so we decreased the dose and looked at other options. Unfortunately, they were all dismal.

We checked on the status of the Ravicti trial and listened to the experience of parents that went through the trial and the results were extremely promising, with almost every child seeing a reduction or complete remission of seizures and many of them reporting better engagement and cognitive improvements in a relatively short amount of time. We knew that this was our best hope at resolving her seizures without sedatives and that this would give her the best chance to change her developmental trajectory. Waiting for the trial results to become official and Ravicti getting FDA approval would take at least a year, maybe longer. That would be a year of Angelina either having seizures or getting hobbled by strong sedatives, so we had to take action.

We talked to our pediatrician, who previously said he was willing to prescribe Ravicti if we had the money, and we came up with a plan. We would get the medication knowing insurance wouldn't cover it and simply pay for it out of pocket for a few months, using the money we had saved for a down payment on our first home. We would take baseline evaluations from the neurologist, pediatrician, and physical therapist. Then after a few months, if the medication made a difference, we would have all the specialties write to the insurance at the same time to make a case for medical necessity. At the lowest recommended dose on the package insert, it would cost nearly $20,000 a month.

We've already gotten the first month's supply and started her on it the day after Mother's Day. Since the second day on it, we haven't seen any of the seizures, and she seems to be much more engaged with us and has gotten up into all fours on her own multiple times as I've typed this out, however it will take more time to know for sure if that is coincidental or actual improvements due to Ravicti

Here is the ask. We have saved enough money to pay for Ravicti for at most three months. This will put us back in purchasing a home by 2-3 years, but it will be worth it if the medication works. The worry is that it might take longer than 2-3 months to show a quantitative improvement that will be enough for the insurance to agree. Insurance may deny the first request, and we may need to repeat the appeal again at 4, 5, or 6 months. They might need to have the official results published from the trial, which might not be until late this year or early next year. We might need a larger dose to see a real difference. I'm setting a goal for what the medication will cost if we need to pay for it out of pocket for 1 year at this dose or six months at a dose close to the high end of the recommended dose. If we get more money than we need, we will donate the excess to the STXBP1 Foundation, which spends 91% of the money raised on research grants. A big part of this is also to spread awareness of what the families of children with rare diseases go through