Identifying the Therapeutic Window in Dravet Syndrome: What the Envision Study Reveals About Early Disease Progression

Joseph Sullivan (00:00): 

My name is Joseph Sullivan. I'm a Professor of Neurology at the University of California, San Francisco, where I work as a Pediatric Epileptologist. So the ENVISION study was another natural history study that was aiming to better define what the natural history is in younger chilchildren with Dravet syndrome. So this study included patients between the ages of 6 months and 5 years. And neurodevelopmental assessments were done periodically over that 2-year period. And again, this was an observational study, so we were able to make changes to background medications, treat their seizures. And really the goal was to not only see how well we're doing with treating seizures given the current standards of care, um, but more importantly, how these young children are doing early in the course of their disease. 

(00:50): 

We know that by definition, patients with Dravet syndrome start off neurodevelopmentally normal, and then we've long seen that there is this deceleration in the rate at which they acquire skills, and then they plateau. And so piggybacking this into the BUTTERFLY study, we have early neurodevelopmental findings that are then extrapolated out to 18 years in the BUTTERFLY study. 

(01:15): 

And what we saw in the ENVISION study was, again, in keeping with what we long felt to be true in clinical practice, that although these kids start off normal and continue to gain skills, the rate of their acquisition of skills really drops off dramatically at around 2 years of age. So this is suggesting that maybe there's an optimal window of opportunity in which to intervene with a disease-modifying therapy. Because if we can intervene sooner during this time when things are declining or the rate of skill acquisition is declining, that's maybe going to extrapolate out many years to even narrow that gap even further. 

(01:56): 

I think another important feature about this natural history study is because it was enriched for younger children that by definition are getting a diagnosis earlier in their disease journey, right? The fact that we actually have some patients that were as young as 12 months of age, I think really highlights that we are doing better as a community in diagnosing these children younger and understanding that natural history in these younger children, I think is going to be really important as we develop some of these disease-modifying therapies moving forward.