Zorevunersen Four-Year Results Confirm Disease-Modifying Potential in Pediatric Dravet Syndrome

Biogen and Stoke Therapeutics presented long-term data from Phase 1/2a and open-label extension (OLE) studies of zorevunersen at the 2025 American Epilepsy Society (AES) Annual Meeting in Atlanta, Georgia, December 5-9. These findings, including new propensity score-weighted analyses comparing treated patients to a natural history cohort, further support zorevunersen’s potential as a disease-modifying therapy for Dravet syndrome by showing durable seizure reductions, more seizure-free days, and neurodevelopmental benefits.

Trial Information

The findings presented by Biogen and Stoke come from their early clinical studies of zorevunersen, including the Phase 1/2a trials and the ongoing open-label extension programs that have tracked patients for up to four years. These studies provided the long-term safety and efficacy results shared at the meeting. The companies also conducted a new propensity-score analysis comparing patients treated with zorevunersen to a matched group from the BUTTERFLY natural history study, offering clearer context on how outcomes differ from typical disease progression. These combined data support the continued advancement of zorevunersen while the pivotal Phase 3 EMPEROR trial (NCT06872125) progresses.

 Across these datasets from the early Phase 1/2a studies and the long-term open-label extension programs of zorevunersen, along with a new propensity-score comparison to the BUTTERFLY natural history study, patients showed sustained reductions in major motor seizures over several years, along with more seizure-free days and improvements or stabilization in key adaptive behavior measures such as communication, daily living skills, and socialization. The propensity score-weighted analysis further showed fewer major motor seizures and better developmental trajectories compared with untreated patients from the natural history cohort, reinforcing the therapy’s potential while the pivotal Phase 3 EMPEROR study continues.

Zorevunersen showed a generally favorable long-term safety profile, consistent with other intrathecal antisense therapies. In the Phase 1/2a studies, treatment-emergent serious adverse events occurred in 22% (18/81) of patients, with all events considered unrelated to zorevunersen except for one suspected unexpected serious adverse reaction. In the OLE studies, no new safety signals emerged; cerebrospinal fluid protein elevation was common but without associated clinical manifestations, and only one patient discontinued because of this finding. Three deaths (two due to sudden unexpected death in epilepsy and one due to malnutrition) were reported across Phase 1/2a and OLE but were assessed as unrelated to zorevunersen.

Scott Perry, M.D., emphasized the growing recognition of zorevunersen’s potential to change the course of Dravet syndrome and highlighted how the new propensity score analysis provides important context on patient improvements under this treatment.

Dravet syndrome is a serious brain disorder that starts in early childhood and causes frequent, hard-to-control seizures. It also leads to problems with thinking, learning, and behavior. This condition is mainly caused by a change in a gene called SCN1A, which affects a protein called NaV1.1 that helps keep brain activity balanced. Because of this, brain cells that usually calm down activity don’t work well, leading to seizures. Even when patients take the best available seizure medicines, more than half still have a lot of seizures, so there is a big need for better treatments that can help both seizures and brain development.

Zorevunersen is an experimental medicine called an antisense oligonucleotide (ASO) that uses Stoke Therapeutics’ TANGO technology to boost production of the healthy NaV1.1 protein from the patient’s normal SCN1A gene copy, directly addressing the genetic cause of Dravet syndrome.

Given by injection intrathecally, Zorevunersen seeks to cut seizures more effectively than current medicines alone while also supporting better thinking and behavior. The FDA has granted it Breakthrough Therapy, rare pediatric disease, and orphan drug statuses, with the EMA providing orphan designation.

Barry Ticho, M.D., Ph.D., expressed confidence in the ongoing Phase 3 EMPEROR program and the upcoming safety and efficacy data from the larger, sham-controlled study, seeing the AES data as further validation of zorevunersen’s promise for patients and families.

Katherine Dawson, M.D., highlighted encouragement from the accumulating long-term safety data with extended dosing and reaffirmed confidence in zorevunersen’s ability to address the root cause of Dravet syndrome and improve symptoms, supporting continued clinical development.​