AAN 2020 Data: Neurostimulation and Adjunctive ZX008

Ian Miller, MD: David Loring and his coauthors are presenting an abstract at the AAN [American Academy of Neurology] 2020 Annual Meeting, which discusses mood and quality of life in patients treated with brain-responsive neurostimulation. The main variable they took into account was whether the individuals were treated early versus late in their epilepsy course, with early and late defined as being within 10 years of epilepsy onset or after 20 years of epilepsy onset. And they compared those 2 groups and looked at the comorbidities within those populations. The notable finding is that individuals who had early treatment of their epilepsy using a brain-responsive neurostimulator device had a much lower incidence of psychiatric comorbidities, including depression. So that’s a really salient finding. It means that it’s important to treat epilepsy as early as possible and aggressively, including brain-responsive neurostimulation if that’s an appropriate therapy for the patient because it makes a difference whether they get it early in their course or late.

What the study means is that early intervention is critically important. Epilepsy is a severe disease, and it has lots of comorbidities that we’re trying to treat, and we like to have the ability to treat both the seizure comorbidity as well as some of the psychiatric comorbidities. And this data set tells us that by treating it early, we can actually affect mood.

Dr Joseph Sullivan and his coauthors are presenting an abstract at the AAN [American Academy of Neurology 2020 Annual] Meeting regarding the long-term safety and efficacy of ZX008, which is fenfluramine, for Dravet syndrome. And they’re reporting their interim results of an ongoing open-label extension study, and that lengthens our follow-up for the patients that were reported in the phase 3 study, which led to or might lead to FDA approval. Their primary findings were that the medication was efficacious and well tolerated. The efficacy was quite startling. It showed a reduction of over 75% in seizure frequency in 37% of study subjects. Effect size is appreciable, and I think it’s much higher than other seizure medications that have been at this point in their approval process.

The other part of the long-term outcome that I was heartened to see was the results of the ongoing cardiac surveillance because this medication was associated with valvulopathy when used in conjunction with phentermine in the past. We had concerns about valvulopathy. The echocardiography for these study subjects, which received a dose starting at 0.2 and was titrated up to a maximum daily dose of 26 mg per day, showed that there was no valvulopathy. All had echocardiography done on a routine basis, and the chance of missing subtle valve changes is very, very low. It was a concern that we had going into the investigational process of a new anticonvulsant medication, and it has really shown nothing of concern.

The primary significance of the data is that the medication is very effective, and for the population being treated that have intractable epilepsy, these are really impressive numbers in terms of the effect size. Not only is the effect size large, but the adverse-effect profile is very favorable. It also failed to document any evidence of valve changes in the 2-year follow-up. That doesn’t mean there won’t be, but it does give us great confidence interval that that incidence is low.