Viva La France

 

I actually have some really great news!

 

Our natural history study for San C was finally approved by the French Committee for the Protection of Persons and CNIL!  You can find the study on NCT#05825131

 

Press release

 

I am over the moon excited to finally be green lighted to start this study. It’s a dream come true! Since we first formed JJB in 2009 our advisors stressed the importance of a natural history study.  We were advise to document the course of the disease and the data could potentially serve as the control arm in a clinical trial.  This is the first ever NHS for MPS IIIC.

Site Initiation Visit, November 6th 2024

 

 

 

Convincing the FDA to accept natural history as a control arm remains to be seen. Change is happening at the FDA; they are finally starting to understand the plight of the ultra-rare. The FDA told us to conduct a natural history study, we have it right there in our meeting minutes.  There is one person at the FDA that is driving the issue, Peter Marks.

 

Dr. Marks is the director of CBER, this is the wing of the FDA that will review our gene therapy program. Last year, I had a nice face to face with Dr. Marks and shared with him the hurdles that San C would have in an interventional trial. I explained to him that San C was even more rare than A and B; diagnosing a child under the age of four without an older sibling being diagnosed first is virtually unheard of. Jonah being an exception.

 

Dr. Marks listened as I explained that the kids in our trials would be symptomatic, they would already have brain damage and the go-to cognitive assessments that the FDA reviewers trusted are not appropriate for evaluating our kids. Furthermore, our kids can be stable for years. I implored to him that it would be highly unlikely to show clinically meaningful change in a two-year trial and there was no way we could afford a trial that lasted more than 2 years. My ask was for him to encourage his reviewers to embrace the power bestowed on them and grant Accelerated Approval (AA).  AA is given by the FDA when a drug demonstrates that it reduces a disease-causing biomarker. In our case that biomarker is Heparan Sulfate (HS). HS builds up in the lysosome of our children’s cells. AA allows the drug company to start selling the drug before full approval.  This allows kids not in the trial to be treated and gives the drug company some revenue to finish out their trial.  Push back from the FDA stems from concern that some drug companies will take advantage of AA. Just recently Ultragenyx received AA for its gene therapy program for the treatment of San A!  This sets precedence for Phoenix Nest to follow.

 

With that said we still must find assessments that show meaningful change. I explained the symptoms of Sanfilippo to Marks and pointed out that we don’t have many endpoints that can be readily measured. Marks advised me to show the reviewers functional improvement. That’s where the video assessment portion of our natural history study comes into play.

 

We created a special protocol that will be used to assess children’s functional abilities at home.  The protocol captures the children performing activities of daily living (ADL’s).  Parents download a medical application onto their phone, consent to the study and follow the directions provided to them. The tech was designed by Aparito and is stored on HIPPA/GDPR compliant software.  We named the app C-RARE, get it C as in Sanfilippo type C, C as in see. RARE stands for Recording Application of Real-world Evidence.

 

Sanfilippo kids have a really hard time sitting still and paying attention to a cognitive assessment administered in the clinic is not practical.  With C-RARE we will capture the child’s true abilities in the comfort of their home. They’ll also visit the clinic and have numerous assessments done.

 

I must share with you the absolute nightmare of trying to get our NHS approved by the French ethics committee and CNIL. Let this story be a lesson for those that want to do the same. 

 

Starting from the beginning.

 

In May of 2022 I went to France and met up with three French type C families at a family conference hosted by the patient organization VML.  France is the perfect country to launch our first NHS site. It has the largest known patient population (except for Brazil) and a compassionate doctor who cares for patients living with San C. Dr. Guffon, is also experienced in running MPS trials.  With the support of Dr. Guffon and help from Aparito, I pitched VML to help fund our NHS in France. The pitch was successful.

 

I went home and started working with Fortrea, our contract research organization. Fortrea manages our trial, they do the medical writing, submissions and regulatory oversight.  We finished the protocol and informed consents and submitted to the French ethics committee in September of 2022. We didn’t receive approval until October 2024! Every time I talk to a parent they ask how long until we can go to interventional trial? Approval for a non-interventional trial took 2 years. I can only imagine how long it will take to get a protocol approved for an interventional trial. I want to start the regulatory process now!

 

The ethics approval process in France is different than the US, in France you’re sent to one of 13 different committees. It’s just luck of the draw. You then get two chances to answer two rounds of questions from the committee. If you don’t answer their questions to their satisfaction, you receive an ‘unfavorable’ opinion and are sent to a different committee to re-submit. If after two unfavorable submissions, you must start all over with a new protocol.  

 

The committees don’t even look at the questions or responses from the other committees, as they are completely independent and therefore have their own opinions. So, expect a whole new round of questions.

 

Our first committee was obsessed with us collecting medical records from families of deceased children. They wanted us to take that out of the protocol.  If we insisted on keeping it in the protocol, then we needed to have a clinical psychiatrist to help the families through the trauma of being asked to donate the records of their deceased child’s medical records. They said that it would be too hard on the families to be asked to participate in the study. They didn’t know it was a parent that designed the study.  The reviewers also didn’t grasp why patients would want to participate in a study that didn’t offer a treatment. They questioned the importance for using so many cognitive and physical assessments. They didn’t have any concept of the hurdles that sponsors creating treatments for ultra-rare, slowly progressing, pediatric diseases were up against.  

 

We had to explain everything in writing.  They refused to talk to us on the phone and allow us to educate them on the importance of a NHS and why we had included so many assessments. We explained all this, then they came back and asked us a whole new set of questions. They set us up to fail. We couldn’t get through another set of questions without exhausting our two tries. They asked us to create a table within the protocol that broke down and explained each assessment and what it was measuring.  We of course had already done this within the protocol in paragraph form. We asked them to be more specific in what they were asking, and they responded we just told you and that was it. So, we created the table and added it to the protocol.  They came back and said we didn’t answer their question correctly and they kicked us to the curb. There were 24 questions in the first committee’s response. We had 2 weeks to respond to all of them and turn it around and have it back translated to French. The process is epic.

 

The second committee was obsessed with the informed consents. They didn’t like the tone in which the assessments were written.  For instance, the infant informed consent was not dummied down to the point that it was baby talk. The adolescent consent was too babyish, and we needed to be more specific on potential risks of blood draw, CSF draw and MRI’s. Giving statistics on how often a CSF draw could cause a headache or the chances of bruising from a blood draw. Remember these patients can’t read or comprehend what the study is about, and the parents will ultimately consent to the study.  In all we had to write 7 different informed consents/assents, each one tailored to the age range of the patient that would be ‘reading’ it. They were obsessed with pregnancy tests; would it be a blood or urine test?  Where would we store the blood or urine? How would we address the pregnancy results with the patient and their caregiver? This review team didn’t act as if they knew that the patients had profound brain damage and would not be able to consent to intercourse, let alone read a consent form. At the end of the day, they refused us because they didn’t agree with the terminology, we used to describe the caregiver of a patient that was a ward of the state.

 

We had to start over, changing the name of the protocol, the study number and making the protocol slightly different so that it appeared to be new. You could imagine how mad I was. I screamed profanities into the emptiness of my office. The person that shares a wall with me won’t make eye contact with me when he sees me in the hall.

 

I informed the patient organizations that were supporting the study; Sanfilippo Sud and VML and sent them the comments. Guilhain, the president of Sanfilippo Sud and one of the co-founders of Phoenix Nest and HANDS took our plight to the French Ministry of Health.

 

Guilhain read that Oliver Veran the government spokesperson and previous minister of health would be speaking at an event near him. Guilhain went to the event, he worked his way through the crowd and grabbed Veran’s attention. He was given five minutes to speak to Dr. Veran, Veran was moved by our story and put him in touch with the current Minister of Health.  Guilhain, was then able to walk the representative through the ethics approval process and share with them the comments of the first two committees.  He was told that they couldn’t tell the ethics committee what to do, but they would certainly investigate it.

 

We resubmitted in July; we had to wait out all of August because everyone in France goes on holiday in August. They reviewed our protocol and informed consents on the 9^th of September and turned around and gave us comments within two days of reviewing our submissions. They asked a couple of minor questions; they didn’t ask us to change anything on the protocol. They did ask us to shorten and combine the informed consents that they were too long for a patient that didn’t have the cognitive capacity to read them and there were too many of them. Go figure…. We fixed the consents and that was it, 2 days later we were given approval.

 

We lost two years and tens of thousands of dollars trying to satisfy the ethics committee. This family here have 2 children, the youngest is the youngest known child in the world. We just lost two years of his life.  Nice work people.

 

We are now in the process of opening a second site in the US at UT Southwestern, Texas. The process is intense as well, we have been warned that it will most likely take 6 months. Our submission date is December 23^rd, with any luck we will be enrolling this summer.

 

Meanwhile, the pre-clinical safety and dose ranging mouse study we started last year is wrapping up. There was concern at the beginning because our mouse model ended up being less severe than we had anticipated. It took longer for us to see behavioral changes in the animals. Fortunately, everything fell into place. Our mice finally got sick, and we were able to show behavioral and survival improvement between our treated and nontreated mice. All the mice are being taken down now and will be shipped off to Australia, where Dr. Fuller will be doing the all-important work of analyzing Heparan Sulfate levels. Woohooo! Next week will kick off the start of the toxicology study. While that study is underway, we hope to write and take our clinical package to the FDA for comments. We need substantial funds for the clinical writing and the clinical grade vector production. Our current NIH grant isn’t enough to pay for the work. With the toxicology data and the data from the mice behavioral and dosage study, combined with the HS analysis we will write yet another grant. I’m confident that we will score high enough to be awarded the grant. Unfortunately, the process of writing and waiting for the NIH grant to be funded will add an extra year to our timelines. Secondly, I’m terrified that the new administration will cut funding to the NIH and we won’t be able to secure federal grants.  

 

I’m very happy with our progress and I expect that we will soon have a clear picture of our path to the clinic. I look forward to updating you in another 6 months.  

 

If so, moved you can help

keep our studies on track by donating to my Giving Tuesday fundraiser.

 

 

 

 

Mutated genes, traumatic labor, and birth defects do not discriminate

I love Jonah and our life together. In this post today I hope to raise awareness for the people with developmental disabilities and those that love and care for them. 

I'm not complaining about my lot in life. 

In situations like ours one parent either quits their job to stay at home with their child or they hire an aid to cover the hours that they're not home. Many families need an extra hand throughout the day and at night.  The out of pocket costs are not realistic for most families. Imagine paying for your child's daycare for the rest of their life. Staying home ends up being the better option.  Which means the family loses a second income.  Which in turns prohibits the family from saving funds for their disabled child's future medical needs or their healthy child's college education. 

"The shape they're in, all the expenses, maybe those kinds of people should just die." -Donald Trump

Sanfilippo syndrome has made Jonah who he is. Jonah brings Jeremy and I tremendous joy and happiness.  Our love for him is profound and we can't imagine him any other way.  To say I wish Jonah didn't have Sanfilippo syndrome is to say I wish Jonah wasn't Jonah.  I don't want Jonah to die and for that I wish he didn't have Sanfilippo. I don't want his body and brain to be ravaged by seizures.  For the dementia to rob him of the ability to walk, talk and eat on his own.  I don't want the sleepless nights to ever start.  I don't want him to have to fight one bought of pneumonia after the next until his lungs give out and his brain shuts down.  No matter what happens... I know that Jonah will always know who Jeremy and I are and he will know that we love him. 

I just want Jonah to live his best life possible.  He deserves that, he deserves the same access to an education, housing, healthcare and services that a healthy child has. To be accepted in his community and treated like a human being by society.

Jonah is aware that he's not like the typical kids at the local playground, he's gotten past that and steers clear of the kids that point out his disabilities. He's never indicated that he's jealous or upset that he can't do the same things they can do. He loves meeting new people, traveling, hosting parties, playing soccer and hanging out with me and his dad. His private school is the best, Jeremy and I feel like we won the lottery with his school. Jonah is happy and we're content being happy that he's happy.

He doesn't recognize you.  Maybe you should just let him die and move down to Florida"- Donald Trump

If I had known during my first trimester of my pregnancy that Jonah had a terminal illness, would I have terminated the pregnancy? I do not know. But if I was pregnant with a second child after the first child was diagnosed and found out that my fetus was also affected, I would most likely terminate. Because our society works against people with disabilities.  The hardships of caring for two terminally ill children would have been financially disastrous. We would have struggled our entire lives trying to make ends meet and provide our children with the necessities of life. 

Today our rights to an abortion are being taken away.  On one hand Trump says that kids like Jonah should just die and on the other he would allow states to deny us the right to terminate a fetus that carries a disease that causes profound cognitive disabilities and need for lifelong medical attention.

Trump appointed three of the nine justices on the Supreme Court, giving the court the conservative majority it needed to overturn Roe V Wade. He says "I was proudly the person responsible for the ending of something that all legal scholars, both sides, wanted and in fact demanded be ended. Roe V Wade, they wanted it ended," -Donald Trump video posted on Truth Social April 8th

Jonah is pushing 18 and we have started the ball rolling for when that days comes. Once he turns 18 we must be legally granted guardianship in order to make decisions for him and to take him to his doctor appointments.  We recently applied for and were granted services through OPWDD Office of People with Developmental Disabilities'.  However, Jonah still needs to be approved for Medicaid before we can access the services, we're working on this process now. OPWDD will help us hire an aid for him and find an adult daycare program for him. During Trump's administration Trump did everything he could to try to abolish the Affordable Care Act which protects Medicaid programs like NYs OPWDD. When the day comes that Jonah can't walk we will need help with medical equipment. For instance we will need special equipment to get him in and out of a tub, I'm thinking we'll need to move to a place with a walk in shower and perhaps a bidet, to clean his bottom. I think I have mentioned Sanfilippo diarrhea in the past.  Wheelchair, safe-bed, seizure monitoring equipment etc. We're going to need all the help we can get and if Trump had his way he'd let Jonah die.

You might think this doesn't affect you, so why should you care. Don't jinx yourself, mutated genes, traumatic labor, and birth defects do not discriminate. You could have passed your disease causing mutation to your children, you just don't know yet. Your new baby grandson could have a stroke during delivery or be deprived of oxygen and be born with brain damage. 

Speaking now to a different kind of childhood death that Trump glazes over. Shortly after taking office, Trump signed into law a bill that reversed an Obama-era regulation that made it harder for people with mental illness to purchase guns.  Trump is incredibly lucky that the kid missed. I wonder how far Thomas Crooks imagined he would get? Shimming up a a building in broad daylight with a rifle hanging over his shoulder and cops all around. Mind blowing, pun intended.  Our society grossly ignores mental health distress. It saddens me to know that Thomas was relentlessly bullied in school.  Perhaps the shooting would never have happened if Thomas had been protected and helped by the adults entrusted to care for him.... Or if he didn't have easy access to a gun... Gun control Donald Trump!  The irony is dumbfounding. Did you know that the number one cause of death for children between 1-19 is from gun related incidences?

I haven't stopped work to take the time and write about the accomplishments and progress that Phoenix Nest has made towards a treatment this past year. I feel bad about that and I hope to get a work post out soon.  Right now I feel compelled to plead with those planning to vote for Trump to think about Jonah and the tens of thousands of families in our position. 

Trump could destroy everything that myself and my rare disease community have worked so hard for.  He can limit NIH funding, he can slow FDA drug approvals, he could take away Medicaid programs, limit funds to special education and influence drug reimbursement. He does not support my son, my small business or my community of families of developmentally disabled children. Based on his first term we have reason to believe that all our programs are in jeopardy. FYI, these are just  concerns for todays post.

The moment that bullet grazed Trump's ear I thought we were done for. The guy would become untouchable and for a few weeks it seemed that way. I started thinking about how I would tolerate the next four years. Our natural history study will take 4 years to complete, I'll just pour myself into work and not look up. Then Biden rose to the occasion and dropped out of the run for office. To my delight Kamala Harris was selected as the new democratic presidential candidate. I feel that a huge weight has been lifted from my shoulders. 

I'd like to acknowledge a fellow Sanfilippo parent that is fighting to raise awareness and protect the rights for those with disabilities through her Instagram account, you can find Noel and Logan Pacl at love_logan007

There are a handful of other courageous Sanfilippo parents raising awareness through social media. I praise them for their dedication and tough skin. My JJB Instagram account is now perkyplantslivehere. I post about my beloved office plants, you can marginalize my plants I can deal with that. I just can't easily or gracefully respond to or rebound from the hurtful posts that strangers made on my personal and JJB posts regarding rare disease.

I'm dedicating this post in loving memory to Jan, Jonah's adoring grandma. Jan's affection for Jonah was unwavering she absolutely adored him. Watching her engage with Jonah was heartwarming. Jan will be deeply missed by all those that loved her. We lost her too soon. I know that Jan would have appreciated this blog. RIP grandma Jan.

Jonah's 16th Birthday