Faster-than-expected enrollment seen in trial testing zorevunersen for Dravet
With large study advancing, Stoke eyes possible approval submission in 2027
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Enrollment in a large clinical trial evaluating zorevunersen for Dravet syndrome is now expected to be completed in the second quarter of this year, earlier than previously anticipated, positioning the therapy candidate for a potential new drug application (NDA) submission in 2027.
That’s according to Stoke Therapeutics, which is leading the drug’s development under a collaboration agreement with Biogen.
The Phase 3 EMPEROR (NCT06872125) study, which began recruiting participants last summer, is evaluating zorevunersen in an estimated 150 children and adolescents with Dravet. The trial is currently enrolling patients at multiple clinical sites in the U.S., Japan, and the U.K. In the double-blind study — meaning neither patients nor researchers know who is receiving the actual medication — eligible participants, ages 2 to 18, are assigned to receive either zorevunersen or a sham treatment.
Based on current enrollment progress, Stoke now says the trial is on track for a data readout in mid-2027. If positive, results from EMPEROR are expected to support a rolling submission of an NDA to the U.S. Food and Drug Administration (FDA) in the first half of 2027, Stoke stated in a company press release.
Zorevunersen was previously granted breakthrough therapy designation by the FDA, a status intended to expedite the development of treatments for serious conditions that show meaningful benefit in early clinical testing.
“The rate of enrollment in the Phase 3 EMPEROR study is highly encouraging and supports the significant need for a disease-modifying treatment for Dravet syndrome,” said Ian F. Smith, Stoke’s CEO and director.
Thus far, according to Stoke, nearly 330 patients have been identified as potential study candidates. Of those, about 60 have already been randomly assigned to treatment, while another 60 have entered the eight-week screening that immediately precedes randomization, the company noted.
“The accelerated timing for completion of enrollment of 150 patients, in addition to breakthrough therapy fesignation, positions us to initiate a rolling NDA submission in the first half of 2027 resulting in the potential to deliver zorevunersen to patients sooner than originally expected,” Smith said.
Stoke continuing to ‘engage’ with FDA on zorevunersen development
As part of the breakthrough therapy status granted to zorevunersen, Stoke held a meeting with the FDA — announced by the company late last year — to review the treatment’s ongoing clinical development and discuss potential options for accelerating its path to patients. While no immediate changes to the development program were made, the agency requested additional information, which the company has since provided, according to Stoke.
Discussions between Stoke and the FDA regarding possible opportunities to expedite development, registration, and delivery of the therapy are ongoing, the company stated.
“Our recent multidisciplinary meeting was productive and we appreciate the FDA’s interest in deepening their understanding of Dravet syndrome and its impacts on patients and their families while also taking time to review and discuss our four years of clinical data,” Smith said. “Subsequently, we have responded to the agency’s request for additional information and we look forward to continuing to engage with them as part of our commitment to explore every opportunity to deliver zorevunersen to patients as quickly as possible.”
A genetic condition, Dravet is mainly caused by mutations in one copy of the SCN1A gene. That gene provides instructions for making a protein part of a brain sodium channel called NaV1.1, which is critical for nerve signaling. When this protein doesn’t work correctly, signaling is disrupted, leading to seizures and other disease symptoms.
Zorevunersen, formerly known as STK-001, is designed to boost production of functional Nav1.1 from the healthy SCN1A gene copy. As such, the therapy is thought to help reduce seizure frequency and improve overall clinical status and quality of life.
In earlier trials, therapy’s use reduced seizure frequency
Zorevunersen has been evaluated across four clinical studies in the U.S. and the U.K. These were the completed Phase 1/2a trials MONARCH (NCT04442295) and ADMIRAL (ISRCTN99651026), along with their respective open-label extension (OLE) studies, SWALLOWTAIL (NCT04740476) and LONGWING (ISRCTN12811235).
Data from the Phase 1/2 trials and their OLEs showed that zorevunersen led to reductions in seizure frequency that were sustained with long-term treatment.
The main goal of the EMPEROR study is now to confirm whether the therapy can reduce seizures after 28 weeks, or about six months, of treatment.
The earlier findings also suggested that zorevunersen may provide benefits beyond seizure control, with improvements reported in measures of cognition and behavior, daily functioning, and overall well-being. These benefits were sustained over a two-year follow-up period. More recent two-year data presented by the company at a medical meeting continue to show durable benefits with the dosing regimen selected for EMPEROR.
