Zorevunersen appears safe and may alleviate symptoms in children with Dravet syndrome

1. In this phase 1/2a trial involving patients with Dravet syndrome who received intrathecal zorevunersen, treatment-related adverse events occurred in nearly half of patients but were generally mild to moderate in severity.

2. Zorevunersen was associated with reduced seizure frequency and improvements in quality of life and overall clinical status.

Evidence Rating Level: 2 (Good)

Study Rundown: Dravet syndrome is a severe developmental encephalopathy caused by reduced expression of Nav1.1 sodium channels. Affected children have reduced quality of life and high rates of sudden unexpected death in epilepsy. Current treatments such as antiepileptic drugs, dietary therapy, and neuromodulation are largely ineffectual in both controlling seizures and addressing nonseizure symptoms. Zorevunersen is an antisense oligonucleotide which promotes increased expression of Nav1.1 sodium channels. The phase 1 MONARCH-ADMIRAL study and phase 2a SWALLOWTAIL-LONGWING study evaluated the safety and efficacy of zorevunersen as a disease-modifying therapy for children with Dravet syndrome. Nearly all patients enrolled experienced at least one adverse event, and approximately one-quarter reported a serious adverse event. Only one serious adverse event was deemed to be related to the treatment, and there were no treatment-related deaths. The most common adverse effects were post-lumbar puncture syndrome and elevated cerebrospinal fluid protein. Seizure frequency was found to decrease in a dose-dependent manner, with those who received the highest dose experiencing a reduction of greater than half compared to baseline. More than four-fifths of participants experienced some improvement in clinical status and quality of life according to both clinician evaluation and caregiver report of improvement. This study was limited by an open-label design, a lack of placebo control, and a small sample size precluding definitive conclusions about efficacy. However, these results demonstrate the potential of zorevunersen as a safe disease-modifying therapy in children with Dravet syndrome. A phase 3 randomized controlled trial is ongoing. 

Click to read the study in NEJM

Relevant Reading: Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome

In-Depth [prospective cohort]: This phase 1/2a study evaluated the safety and efficacy of zorevunersen in children and adolescents with Dravet syndrome. A total of 81 patients were enrolled in the phase 1 trial, with 75 continuing on to the phase 2a trial. Participants received varying doses of intrathecal zorevunersen – either a single dose between 10 and 70 mg or two to three doses of 20 to 70 mg across three months. Primary endpoints were safety profile and pharmacokinetics, and secondary endpoints included change in seizures from baseline and caregiver-reported quality of life scores. Overall, 96% of phase 1 participants and 100% of phase 2 participants experienced at least one adverse event, which were mostly mild to moderate in severity. Treatment-related adverse events were reported in 30% of phase 1 participants and in 53% of phase 2 participants. Serious events were reported in 22% of the phase 1 group and 29% of the phase 2 group, with one event of neurologic decompensation thought to be related to the treatment. Three patients died from complications of their underlying Dravet syndrome. The median change in seizure frequency was highest in patients receiving 70 mg doses, with a median change at 6 months of -57.3% in the single-dose group and -73.6% in the multiple dose groups. More than 80% of patients experienced some clinical improvement from baseline according to both clinician and caregiver assessments. Overall, these results showed that zorevunersen was safe and demonstrated efficacy for seizure and nonseizure symptoms in children with Dravet syndrome.

Image: PD

©2026 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.