Dravet Syndrome: Drug Development Overview
Dravet syndrome: from symptom control to disease modification?
Short summary:
- High unmet need remains despite several approved therapies.
- The pipeline is transitioning from anti-seizure therapies to disease-modifying approaches.
- Different modalities are competing to solve the same biological problem.
International Dravet Syndrome Day marked the focal point of Dravet Syndrome Awareness Month (June 23). Against a backdrop of growing innovation in the field, the past year has delivered several noteworthy developments that may help shape the future treatment landscape for patients with Dravet syndrome.
Dravet syndrome is a rare and severe developmental and epileptic encephalopathy most commonly caused by mutations in the SCN1A gene and that typically begins during the first year of life. While recent years have brought meaningful advances in seizure control, the disease continues to impose a substantial burden through persistent seizures, developmental delay, cognitive impairment, and behavioral comorbidities.
Current management is based on individualized combination therapy, with valproate (broad-spectrum antiepileptic), clobazam (GABA-enhancing benzodiazepine), stiripentol (GABAergic modulator and enhancer of concomitant therapies), fenfluramine (serotonergic modulator), and cannabidiol (endocannabinoid pathway modulator) forming the backbone of treatment according to recent expert consensus recommendations. In contrast, sodium channel blockers are generally avoided, as they may further impair the already dysfunctional NaV1.1 channels associated with SCN1A mutations.
Despite advances, significant unmet need remains.
Long-term natural history data from the BUTTERFLY study, published in late 2025, highlight a key challenge: despite treatment with today's standard of care, many patients continue to experience significant seizure burden while neurodevelopment often plateaus, reinforcing the need for therapies that address the underlying biology of disease rather than symptoms alone.
This is where the next generation of therapies may change the landscape.
- Bexicaserin (Lundbeck)
Bexicaserin is a selective 5-HT2C receptor agonist designed to reduce neuronal hyperexcitability through modulation of serotonergic signaling pathways. Following encouraging Phase 2 data demonstrating substantial reductions in seizure frequency across developmental and epileptic encephalopathies, the therapy has advanced into the global Phase 3 DEEp SEA study in Dravet syndrome. Unlike SCN1A-targeted approaches, bexicaserin does not aim to correct the underlying genetic defect but seeks to further improve seizure control through a novel mechanism, potentially expanding treatment options for patients whose seizures remain inadequately controlled despite current therapies.
- Zorevunersen (Stoke Therapeutics)
In March 2026, data published in the New England Journal of Medicine reported sustained seizure reductions and encouraging signals in cognition, communication, and adaptive behavior. Following alignment with FDA, EMA, and PMDA on the Phase 3 EMPEROR trial design in early 2025, zorevunersen has emerged as one of the leading disease-modifying candidates in Dravet syndrome.
- ETX101 (Encoded Therapeutics)
ETX101 is a one-time gene regulation therapy designed to increase expression of the healthy SCN1A copy. Following FDA Breakthrough Therapy designation in January 2026, ETX101 advanced into the Phase 1/2a ENDEAVOR study in April 2026, becoming the first gene therapy candidate ever to enter clinical development for Dravet syndrome.
Taken together, recent developments suggest that the Dravet field may be entering a new era. While seizure control remains essential, the focus is increasingly shifting toward therapies that could alter the course of disease itself and potentially improve developmental outcomes for patients and families.
Honorary mention:
- ION337 (Ionis Pharmaceuticals)
In April 2026, Ionis initiated a Phase 1/2 study of ION337, another antisense oligonucleotide designed to increase SCN1A expression. While still at an early stage, the program highlights growing industry interest in addressing the genetic root cause of Dravet syndrome rather than symptoms alone.