Staying Resolute in Challenging Times
Our Rett community is grieving and understandably concerned about the recent death of a young girl participating in the Neurogene clinical trial.
Over the last week, I’ve been asked three questions repeatedly:
- Why did this happen?
- Where do we go from here?
- What can I do?
These questions don’t have simple answers. This situation is a sobering reminder that clinical trials, while they carry the potential for great positive change for all our loved ones, also come with risks. What I do know is that it remains essential to continue our pursuit of scientific advances that will deliver transformative genetic medicines. My colleagues and I remain resolute in our commitment.
Below, I’ve shared some information that I hope you’ll find helpful.
Why did this happen?
The young girl who participated in the trial experienced a serious adverse event (SAE) called systemic hyperinflammatory syndrome. Experts have described this type of event as a rare but known severe immune reaction to adeno-associated virus (AAV) gene therapies, in this case AAV9. It’s important to note that the SAE was caused by the amount of virus, AAV9, that was injected. It was not caused by the MECP2 gene inside the AAV9.
In almost all clinical trials, clinicians want to determine how much of a medicine is required to derive the largest benefit with minimal side effects. The trial was testing two doses, a low dose (1e15) and a high dose (3e15). This child was the third person to receive the high dose. The first two children who received the high dose did not experience a SAE.
For context, Zolgensma, the gene therapy for spinal muscular atrophy, also uses AAV9. It has been administered to more than 4,000 patients at roughly the same dose as the one used in the Neurogene trial. Two children who received Zolgensma died from treatment related reaction.
According to Neurogene:
- There have been no other serious side effects in the clinical trial
- Importantly, the U.S. Food and Drug Administration has not halted the study and dosing will continue at the lower dose level
- In a low-dose group, four participants showed meaningful gains of skills and developmental milestones
- The company is committed to continuing the development of NGN-401 as well as learning as much as possible about why the SAE happened
Where do we go from here?
As we reflect on what this means for our community and therapeutic development moving forward, we mourn the loss of this child. We also must not lose sight of our collective mission – to bring transformative new medicines to children affected by this serious, lifelong neurological disorder.
We look to other rare diseases who have also fought to seek therapeutics for their children. Several rare disease communities have experienced serious side effects or deaths and gone on to have not just one, but multiple genetic medicines approved.
The root cause of Rett syndrome is well understood. We remain optimistic that targeting this underlying cause with genetic medicines will be life-changing for our children and everyone who loves them. Time is of the essence and achieving success depends on continuing this work.
What can I do?
Families with questions and concerns about the clinical trial can contact Neurogene here:
1-877-237-5020
patientinfo@neurogene.com
In difficult times, it's not uncommon to feel a sense of helplessness. A tangible way for families to combat this feeling is to participate in studies that advance our understanding of Rett syndrome. The more we learn about Rett, the better all clinical trials and genetic medicine development programs will be.
