BEDFORD, Mass. & CAMBRIDGE, Mass. — New clinical data published in The New England Journal of Medicine suggest that the investigational RNA therapy zorevunersen may have the potential to modify the course of Dravet syndrome, a rare and severe genetic neurodevelopmental disorder characterized by frequent seizures and developmental delays.
The findings were reported by Stoke Therapeutics Inc. and Biogen Inc., which are jointly developing the therapy. The publication includes results from completed Phase 1/2a studies and ongoing open-label extension trials evaluating the treatment in people living with the disease.
According to the companies, patients treated with zorevunersen experienced substantial and sustained reductions in seizures, along with improvements in cognition and behavior. These effects began during the Phase 1/2a treatment period and continued through as long as three additional years of follow-up in the extension studies. Participants received the therapy alongside standard anti-seizure medications.
Dravet syndrome is a severe developmental and epileptic encephalopathy in which children experience frequent seizures beginning in infancy and a plateau in neurodevelopment around the age of two. As they grow older, many patients fall further behind typical developmental milestones. Currently, no approved treatments directly modify the underlying cause of the disease.
“These data mark a potential turning point in the treatment of Dravet syndrome,” said Helen Cross, MB ChB, Ph.D., corresponding author of the NEJM publication and The Prince of Wales’s Chair of Childhood Epilepsy and Director of University College London Great Ormond Street Institute of Child Health, Honorary Consultant in Paediatric Neurology at Great Ormond Street Hospital. “While reducing seizures is still critical, the improvements in cognition, behavior and quality of life seen in these studies suggest we may be changing the course of the disease and therefore the lives of patients and their families.”
The Phase 1/2a trials evaluated both single and multiple doses of zorevunersen of up to 70 mg, primarily to assess safety. Reductions in major motor seizure frequency were evaluated as a secondary endpoint. Researchers observed the most substantial seizure reductions among patients who initially received 70 mg doses in the early-stage studies, with benefits continuing through three years of follow-up.
Investigators also measured changes in neurodevelopment, clinical status, daily functioning and quality of life. Assessments showed improvements in communication, motor skills, socialization and daily living abilities over the extended treatment period.
Zorevunersen was generally well tolerated in the studies. A total of 81 patients received at least one dose of the therapy, with more than 800 doses administered across the trials. The most common treatment-related adverse event was elevated cerebrospinal fluid protein levels, which occurred in 44 percent of patients in the extension studies. One patient discontinued treatment because of elevated protein levels, and most serious adverse events were determined to be unrelated to the therapy.
“The discovery of the genetic cause of Dravet syndrome 25 years ago changed how researchers thought about the disease and how to treat it,” said Barry Ticho, M.D., Ph.D., Chief Medical Officer of Stoke Therapeutics. “By targeting the underlying genetic cause of the disease, zorevunersen has the potential to be the first disease-modifying medicine for the treatment of Dravet syndrome. We look forward to the results of our Phase 3 EMPEROR study expected in mid-2027.”
“This publication in NEJM demonstrates an appreciation of the severity of Dravet syndrome and the potential of this novel approach to transform the way the disease is treated,” said Katherine Dawson, M.D., Head of Therapeutics Development Unit at Biogen. “For more than 10 years Biogen has been advancing cutting-edge research to address some of the most rare, devastating and neglected diseases, and we are proud to partner with Stoke on this first-of-its-kind investigational drug.”
