Beyond Seizures: Zorevunersen’s Impact on Cognition and Function

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 third episode, Perry highlighted how zorevunersen produced measurable gains on the Vineland-3 adaptive behavior scale across multiple domains, especially expressive and receptive language. He delved into the significance of this scale, noting that modest score increases of 2–3 points were deemed clinically meaningful by both clinicians and caregivers. These data suggest that the therapy may influence neurodevelopmental outcomes, not just seizure control—a key shift in the treatment paradigm for Dravet syndrome.

Transcript edited for clarity.

Scott Perry, MD: The early phase 1/2a trials included several outcome measures beyond seizures, such as the Vineland-3, caregiver and clinician global impression of change, and quality-of-life assessments. The Vineland-3 is particularly important because it captures communication, socialization, coping, and motor skills—areas that families consistently cite as top priorities.

In both the Admiral and open-label studies, we saw significant improvements across multiple Vineland domains, most notably in expressive and receptive communication. These gains continued year over year—at 12, 24, and 36 months—indicating sustained benefit.

To help interpret what those changes mean, researchers surveyed clinicians and caregivers to determine what constitutes a “clinically meaningful” improvement. Both groups agreed that changes of 2–3 points represented meaningful progress, and zorevunersen achieved that across several domains. This suggests we’re seeing benefits that extend well beyond seizure reduction.