Stoke Therapeutics, Inc. has announced that it has achieved alignment with global regulatory agencies, including the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA), and Japan’s Pharmaceuticals and Medical Devices Agency (PMDA), for the design of its phase 3 Emperor study of Zorevunersen. This study aims to potentially be the first disease-modifying medicine for the treatment of Dravet syndrome.
The proposed Emperor phase 3 study will evaluate two loading doses of 70mg followed by two maintenance doses of 45mg over 52 weeks compared to sham in children and adolescents ages 2 to <18 with Dravet syndrome. The primary endpoint will be a reduction in major motor seizure frequency, with key secondary endpoints including improvements in cognition and behavior as measured primarily by Vineland-3. The company plans to initiate the phase 3 study in mid-2025.
Zorevunersen was recently granted FDA breakthrough therapy designation, positioning it on an efficient development path. Clinical data support the phase 3 dosing regimen, with patients treated with the drug in previous studies experiencing an 87% median reduction in convulsive seizure frequency at month eight. Patients also experienced continuing improvements in multiple measures of cognition and behavior as measured by the Vineland-3 through two years of treatment.
The Emperor pivotal phase 3 study will be a global, randomized, double-blind, sham-controlled trial with an anticipated enrollment of approximately 150 patients with Dravet syndrome between the ages of 2 to <18 years of age. The primary endpoint will be the percent change from baseline in major motor seizure frequency in patients receiving Zorevunersen compared to sham, with key secondary endpoints including durability of effect on major motor seizure frequency and improvements in behavior and cognition as measured by Vineland-3 subdomains.
Dravet syndrome is a severe developmental and epileptic encephalopathy, characterized by frequent, prolonged, and refractory seizures, and is difficult to treat. The syndrome is also associated with developmental and cognitive impairments, intellectual disability, movement and balance issues, language and speech disturbances, growth defects, sleep abnormalities, disruptions of the autonomic nervous system, and mood disorders. People living with Dravet syndrome have a higher risk of sudden unexpected death in epilepsy (SUDEP), and there are currently no approved disease-modifying therapies for the condition.
Zorevunersen is an investigational new medicine for the treatment of Dravet syndrome currently being evaluated in ongoing clinical trials. Stoke Therapeutics is developing antisense oligonucleotides (ASOs) to selectively restore protein levels, with its first compound, Zorevunersen, in clinical testing for the treatment of Dravet syndrome.
Stoke Therapeutics is hosting a webcast and conference call for analysts and investors to discuss the successful alignment with global regulatory agencies related to the phase 3 study of Zorevunersen. The webcast will be available on the investors' section of Stoke’s website, and a replay will be archived and available for at least 90 days following the event. As a result of these announcements, the company's shares have moved -14.5% on the market, and are now trading at a price of $9.42. Check out the company's full 8-K submission here.
