Clinical trials are HARD. How many times have you heard that? But it’s true. Expectations, anticipation, screening, burden of participation with frequent clinic visits, blood draws, outcome measures and waiting for news.

This year has been a series of hard knocks.

We learned about Pfizer’s SAE (serious adverse event) during PPMD’s June meeting and thankfully, by that time, the individual was out of the hospital and doing well.

Just a few weeks ago, Roche terminated their anti-myostatin study because, statistically, it failed the primary outcome measure. We have so many questions and are hopeful for further analysis to understand if a sub-group of individuals improved.

And earlier this week, Solid reported an SAE in their gene therapy study. We are reminded of the statistics about the potential for trials to fail – FDA states 9 out of 10 drugs that make it to the registration stage fail – but this community is about HOPE and PROGRESS.  This is why we continue to participate in trials, continue to believe in treatments, continue to learn from the past.

Early Days

In the scheme of things, our community is still in the ‘early days’ of research, especially when you talk about something as new as gene therapy. Early days. These words are repeated on a loop in my head.  This means that the clinical trials have just begun.

It is not that the concept of gene-based therapies is new for us. We have watched this technology evolve as people were identified that were living with and flourishing with a mutation in their dystrophin gene, mutations that led to truncated dystrophin production rather than a complete absence. Constructs have been and are being developed to mimic those efficient truncated proteins, synthetic versions of the dystrophin protein. This is followed by testing in cell culture, in animal models, figuring out a delivery vehicle, and a ‘driver’ or promoter to target relevant tissue.

We are familiar with dose-ranging studies, the high dose studies delivering a quadrillion or so virus particles carrying DNA, a promoter that is the driver to certain specific tissues and a ‘payload. ’ This is the basis for the micro-dystrophin construct. Can you even fathom a quadrillion particles of virus?

With Every Answer, a List of Questions

I’m sure, like me, you have loads of questions…

Around immunity:

• How is it measured?
• How is the measuring different between companies?
• Should a person fail inclusion based on antibodies, are there ‘work arounds’ and when do we anticipate studies for these individuals?

Around inclusion criteria:

• When will inclusion be expanded to older patients? Younger patients?

Around outcome measures:

• Are they sufficiently sensitive?
• Will it take years to understand benefit?

Around safety:

• What are we learning about safety issues, response to the virus, response to the micro-dystrophin?
• Is there a way to screen for those who might have a safety issue?

Around re-dosing:  

• How long will the effect last? How will we know?
• How will we re-dose?

And these are just questions off the top of my head. I’m sure there are many others.

Like everything in Duchenne, it is unlikely that all individuals will have a similar response as there is a great deal of variability in progression and we are in (here’s that phrase again!) ‘early days’ identifying mutations that result in differences in progression and other genes that modify disease progression.

Early days. Baby steps. But look where we are now. Progress being made in all therapies, including gene therapy. There will be bumps on the way, but we are climbing this mountain. Slowly, but together.  And one day, we will run. Because of the significant learnings behind us and those to come, always grateful to the families that participate in these trials, pushing us closer to our goal. A day when an individual’s electronic health record (EHR) indicates HAD Duchenne. When their EHR states: “Past Medical History – Duchenne muscular dystrophy.”

The day that we #EndDuchenne.