Stoke Therapeutics Shows Zorevunersen Reduces Seizures and Improves Cognition in Dravet Syndrome

Stoke Therapeutics, Inc., a biotechnology firm focusing on RNA medicine, has presented promising new data on zorevunersen (STK-001) at the 15th European Epilepsy Congress (EEC). The data highlights significant and sustained reductions in seizures and improvements in cognition and behavior in patients with Dravet syndrome, a severe genetic epilepsy. 

Dravet syndrome is characterized by frequent, prolonged seizures that begin in the first year of life, leading to developmental delays and cognitive impairments. The disease is classified as a developmental and epileptic encephalopathy, and there are currently no approved disease-modifying therapies. It affects approximately one in 16,000 infants worldwide.

Zorevunersen, an investigational therapy, has shown potential as the first disease-modifying treatment for Dravet syndrome. It works by upregulating the NaV1.1 protein expression, which is deficient in patients due to a mutation in the SCN1A gene. This approach aims to restore normal protein levels, thereby reducing seizures and improving cognitive and behavioral outcomes.

In the Phase 1/2a ADMIRAL study, patients treated with zorevunersen experienced notable improvements in cognition and behavior during the first year of treatment, with further increases observed as treatment continued. This was complemented by a two-year natural history study showing that despite standard anti-seizure medications, patients with Dravet syndrome continued to have high seizure rates and stalled neurodevelopment, widening the developmental gap compared to their neurotypical peers.

Helen Cross, MB ChB, Ph.D., a leading investigator in the ADMIRAL study, emphasized the significance of these findings, noting that the reductions in seizures and improvements in cognition and behavior represent a breakthrough in Dravet syndrome treatment. Barry Ticho, M.D., Ph.D., Chief Medical Officer of Stoke Therapeutics, pointed out that current anti-seizure medications are inadequate, as evidenced by the high seizure rates and developmental delays in patients. The data from their studies suggest that zorevunersen could substantially reduce seizures and offer cognitive and behavioral benefits, which have not been seen before in clinical studies for Dravet syndrome.

The studies presented also highlighted the tolerability of zorevunersen across the trials. The ADMIRAL study included children and adolescents aged 2 to 18 with a confirmed SCN1A mutation. The study aimed to assess the safety, tolerability, and pharmacokinetics of the drug, as well as its efficacy in reducing convulsive seizure frequency. Participants who completed the ADMIRAL study were eligible to continue treatment in the LONGWING open-label extension (OLE) study, which evaluates the long-term safety and effects of zorevunersen.

The BUTTERFLY observational study also provided valuable insights, showing that despite the best available anti-seizure treatments, patients did not experience significant improvements in seizure frequency or cognitive and behavioral development. This further underscores the need for a disease-modifying therapy like zorevunersen.

Stoke Therapeutics is committed to developing RNA-based treatments for haploinsufficiencies, diseases where a loss of approximately 50% of normal protein levels leads to disease. Their proprietary TANGO (Targeted Augmentation of Nuclear Gene Output) approach aims to restore protein levels selectively. Zorevunersen is currently in clinical testing, and the company is also developing STK-002 for autosomal dominant optic atrophy (ADOA), an inherited optic nerve disorder.

The promising results from these studies provide hope for a new era in the treatment of Dravet syndrome, with zorevunersen potentially offering substantial improvements in seizure management and overall neurodevelopmental outcomes.

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