The Future of Disease-Modifying Therapy in Epilepsy

Zorevunersen is an investigational antisense oligonucleotide therapy being studied for Dravet syndrome, a developmental and epileptic encephalopathy caused primarily by pathogenic variants in the SCN1A gene. By modulating RNA splicing to enhance production of functional sodium channel protein, zorevunersen is designed to target the underlying genetic mechanism of the disorder. Early clinical studies have suggested reductions in seizure frequency and signals of improvement across adaptive behavior measures, warranting further investigation in phase 3 evaluation.

In this NeurologyLive^® Special Report mini-series, Scott Perry, MD, Co-Director of the Jane and John Justin Neurosciences Center at Cook Children’s Hospital, reviews the available evidence and ongoing research surrounding zorevunersen. Across five focused episodes, Perry discusses its molecular rationale, early-phase trial findings, clinical outcomes beyond seizure control, the design of the ongoing EMPEROR trial, and what these developments may mean for the future management of Dravet syndrome.

In this final segment, Perry provides commentary on how the field is evolving beyond seizure suppression to address underlying disease mechanisms. He anticipates more clinical trials will include developmental and functional endpoints, alongside the emergence of genetic therapies targeting root causes. The discussion highlights a broader transformation in epilepsy care—one focused on improving overall quality of life and long-term neurological outcomes.

Transcript edited for clarity.

Scott Perry, MD: I think we’re going to see more therapies like zorevunersen—treatments that go beyond symptom management to address the underlying biology of epilepsy. We’ve already seen seizure-focused drugs beginning to explore whether they can also improve cognition or development, and I think that will become a more consistent focus.

More importantly, there’s growing interest in designing therapies that directly target genetic causes, as that’s where we expect the greatest impact. Multiple programs are now exploring this approach not only for Dravet but for other developmental and epileptic encephalopathies.

Over time, I think we’ll see this shift reflected in how we design clinical trials, measure outcomes, and define success for our patients.