Since JJB came into existence there have been 7ish Sanfilippo trials.
Please, do your own fact checking, everything I say here is off the top of my head. Don’t hang me with a meme. I admit that my memory recall is not always 100% accurate, it’s up to you to do your own due-diligence!
February 2017, Alexion/Synageva shelved its Enzyme Replacement Therapy (ERT) for MPS IIIB. Around the same time, UniQure decided to disband their gene therapy program for MPS IIIB before even taking the leap to clinical trial. November 2018, Shire shut down their ERT for MPS IIIA, citing that they failed to improve neurocognitive activity in infants and children in early stages of Sanfilippo.
The second wave of Sanfilippo clinical trials have been in upheaval, BioMarin announced that they were divesting their ERT drug, Tralesinidase for IIIB. A huge shock to our community. Fortunately BioMarin was able to work out a deal with Allievex. The trial will continue without pause, a huge sigh of relief. Congrats to all of the families participating in the trial, I hope that all your dreams come true! Sad to say, Sobi’s MPS IIIA ERT trial is still in flux. Hoping for a Christmas miracle on that one.
Can you imagine being told your child has a terminal illness and there is no treatment? Then miraculously a treatment goes to trial and your child is accepted into that trial! I’d be dancing for joy, screaming from the rooftops: “My child has just received a second chance at life!”
Some families have to relocate to be closer to the trial center, their lives and careers uprooted. Now imagine being informed that the company has had a change of heart and is moving in a new direction. Sorry.. this drug will run out and will no longer be available to your child. That's what happened to the families in the Shire and Alexion trials. Sobi…
This news would destroy me. Diagnosis day all over again, with the caveat, this drug might be a able to stabilize your child. Regrettably, we don’t have the bandwidth to see it through.
Phoenix Nest is creating an ERT for MPS IIID and a gene therapy for MPS IIIC. What makes me think that the treatment my company is creating will make it through clinical trial and onto commercialization? At times I feel like the deer caught in headlights. Survival instincts kick in, run as fast as you can.
One of Jonah’s favorite books is about the gingerbread boy. Do you know it? Run, run as fast as you can, you can’t catch me, I’m the gingerbread boy. In that book the Fox gobbles up the gingerbread boy. But in the sequels the gingerbread girl and the gingerbread baby, they learn from their brothers mistakes and outfox the fox. Jonah reads that book to me and recites, run run as fast as you can, you can’t catch me, I’m the Gingerbread Baby! So darn cute, my heart swells and I giggle. Jonah recites that line with such glee and passion, I want to believe with all my heart that Jonah and I will outfox the fox. Jonah has made it this far.
Why can’t we get a Sanfilippo treatment over the finish line?
I think drug companies are setting their drug up for failure by using cognitive endpoints as the end all to be all determinant. If you use cognitive decline as your endpoint, you’re missing the point.
Jonah, now 11 is cognitively at the same level as he was at the age of six. For the past five years he has remained the same, no better, no worse. A gene therapy clinical trial is a one time dosage, normally the FDA would follow the child for a couple of years before granting an approval. If Jonah was on a two year trial, we could say that the drug worked, because Jonah is already stabilized. His cognitive score would not have changed.
Our kids can be progressing perfectly one day, get pneumonia the next and stop speaking a month later. You’ve seen my posts, some kids pass in their sleep no sign of an illness beforehand, just gone before daybreak. I do not reference this callously, follow me to the end. We have no idea when our children will pass, the only certainty is that they will pass.
Our disease is too slow in it’s progression to get through a clinical trial in a feasible timeline and is too heterogeneous for us to use typical FDA measurements. As it stands Sanfilippo does not have an approved biomarker and to that, we don’t have any ‘good’ endpoints to measure. Sanfilippo syndrome is a serious conundrum for the FDA. Meanwhile our kids are dying. It falls on the patient community to scream from the roof tops: Help us! We do actually have a good biomarker, it's just not an FDA approved biomarker, Heparan Sulfate.
Our trials lean hard on cognitive testing assessments like the Baley, Kaufman and Vineland. It’s unfair to expect a child with profound behavioral and cognitive dysfunctions to perform on these tests. Jonah might perform above and beyond expectations one day and horribly the next. What they can accomplish at home might be completely different in a classroom setting. The first time Jonah had one of these tests was right after diagnosis. Jonah was meeting his developmental milestones then, but his behavior was off.
Most all children fear something. Sanfilippo children have irrational fears they might be terrified of: dogs, cattle, running water, Santa or clowns. For years Halloween was a straight up no go in my family. Jonah fortunately has moved past his fear of dogs.
A Sanfilippo child can’t be consoled by a parent, fighting mom or dad off and running into traffic is their instinct. If your child bites you to escape your protective embrace to save themselves from a dog only to be hit by a car… You have a problem or two. Irrational fears are not the same as rational fears. Monsters in the closet, ghosts, getting lost, meteorites crashing into Earth, robberies, parents dying in a car crash or Trump winning another election. These are all rational fears. Sanfilippo children at any age don’t understand death, nor can they comprehend what would happen if a rock hit the Earth.
Getting back to Jonah’s first cognitive testing appointment. The room was small, it felt like a closet sized library without windows or air circulation. Jonah was 2 years old, no cognitive regression, but Sanfilippo was why he was there. For transparency sake, Jonah also had the flu that day. In walks his the facilitator, she looked us in the eye, introduced herself and shook our hands. The facilitator had heterochromia i.e. her eyes were two different colors. The situation did not go over very well for Jonah. Jonah was beside himself, he tried and tried to escape. He wouldn’t calm down. I was removed from the room, reason said I was a distraction and Jonah was feeding off of me. It hurt me to leave Jonah in this state, he was terrified. I justified my departure, Jonah would get over it and hopefully the doctor would learn her lesson.
I sat in the waiting room listening to Jonah scream bloody murder on the top of his lungs for 20 min. Jonah did not relent, I decided it was now child abuse and I walked to the room to rescue him. Before I could knock- the doctor opened the door. Her face was flushed, hair wet and her wild eyes blood shot. She apologized profusely. I looked at her smugly as Jonah threw himself in my arms. Walking away, I realized that the doctor hadn’t a clue as to the real cause of Jonah’s terror. I should have told her that no matter how hard she tried or how good Jonah felt, Jonah would not have followed her instruction. You can’t expect a cognitively impaired child to focus and follow your instruction when you have one brown eye and one blue eye. You make no sense to Jonah, to him you’re a trick question. *I had hoped that I didn't have to apologize for pointing out someones physical difference. Absolutely no disrespect to anyone with heterochromia! Heterochromia is by far the coolest physical change that one could be blessed with. Don't call me Firgie and I won't call you Bowie.
The system doesn’t work for us. What do we do when something doesn’t work? Fix it!
The FDA has already thrown us a bone by creating a 'guidance' for situations like ours the guidance is called: “Slowly Progressive, low-prevalence rare Diseases with Substrate Deposition that Results from Single Enzyme Defects.” It was released July 2018 an update in response to the 21st Century Cures act. The Orphan Drug Act and Pediatric Review Vouchers were also created and approved to help inspire Pharma to develop drugs for rare diseases.
A rare disease is defined by the FDA/USA as a disease that has an incident rate of 1 in 1,500 births. Sanfiippo Syndrome type C has an incident rate of 1 in 1,500,000. If you had a drug company which disease would you choose to create a treatment for? By the way there are 7,000 rare diseases to choose from. This is a problem!
An Uber Rare disease needs even more incentives then a rare disease. Children like Jonah should not be punished because they have a disease that is too rare to make huge sums of money off of. Jonah has a terminal illness. He could die in his sleep or he can carry on like he is for another decade. Again he should not be punished for having a disease that progresses too slow to follow during a typical clinical trial.
We must adapt the measurements that the FDA uses to approve drugs, to measurements that fit the disease. Evidently, I complained about the injustice of our situation to the right people. I got a call from the FDA a few weeks ago inviting me to present my thoughts on how I think things could be done better. I told the agency that I wasn’t going to sugarcoat my speech. I was surprised to learn that the organizers also read my previous blog and they still wanted me. The date of the meeting hasn't been publicly announced yet. But when it is announced I'll share. You can come in person or stream it live, our rare disease community needs your support. The FDA runs on tax payer dollars, they want to know that you care too.
There is so much work to be done. I look to Jonah and our families for motivation. Jonah is doing incredibly well, he is a miracle. I admit we're greedy, we want many many more good days with our son.
The Cure Sanfilippo Foundation created a very successful Giving Tuesday FaceBook holiday fundraiser, JJB and HANDS joined in, together we raised over $130,000 for Sanfilippo research.
I’m forever thankful to all of you that donated in honor and in memory of our kids. It’s a huge relief to know that we still have people supporting our efforts. It’s been a long hard battle and it will continue to be so. We need you. https://curesanfilippofoundation.org/meet-the-families/jonah/DONATE HERE
I was 1,250 shy of making my $5,000 goal. #MoreGoodDays
