Stoke, Biogen team to advance zorevunersen for Dravet patients
Global Phase 3 trial of potential therapy expected to begin by midyear
Stoke Therapeutics and Biogen are teaming up for the further development and potential commercialization of zorevunersen, an experimental treatment for Dravet syndrome that’s moving into late-stage clinical testing.
“With Biogen’s deep experience in neurology and track record of success in commercializing high-value disease-modifying medicines for rare genetic diseases globally, we aim to lead the treatment of Dravet syndrome into a new era by delivering zorevunersen to all patients who could benefit,” Edward M. Kaye, MD, Stoke’s CEO, said in a press release from the two companies.
A global Phase 3 clinical trial of zorevunersen in children with Dravet is expected to launch this year, following findings that support the therapy’s likely efficacy — a decline seizure frequency — in patients treated in two Phase 1/2 studies.
Zorevunersen seen as potential disease-modifying therapy for Dravet
Under the partnership agreement, Stoke will lead clinical development of zorevunersen, and if the therapy goes on to be approved, Stoke will retain rights to commercialize it in the U.S., Canada, and Mexico. Biogen, meanwhile, will hold marketing rights in the rest of the world. Stoke will receive an upfront payment of $165 million, with the potential for an additional $385 million if development and commercialization milestones are met. The two companies will share costs related to external development of the therapy.
Dravet syndrome is caused by mutations in the gene SCN1A, which is needed to make a protein that forms a subunit of a sodium channel called NaV1.1. These mutations cause NaV1.1 to be dysfunctional, leading to problems with nerve signaling that ultimately lead to seizures and other disease symptoms.
Everyone inherits two copies of the SCN1A gene, one from each biological parent. In people with Dravet syndrome, only one copy of the gene is mutated — the other copy is healthy, but it cannot fully compensate for the mutated copy. Zorevunersen, formerly known as STK-001, aims to boost the activity of the healthy copy of the SCN1A gene, allowing for production of more healthy NaV1.1 to help normalize nerve signaling.
Zorevunersen has been designated a breakthrough therapy by the U.S. Food and Drug Administration, a status that aims to speed the development of treatments for serious conditions that show promise in early clinical testing.
Stoke has funded two Phase 1/2 trials of zorevunersen in Dravet patients: MONARCH (NCT04442295) in the U.S. and ADMIRAL (ISRCTN99651026) in the U.K. Those trials are completed, and patients are continuing to be followed in the extension studies SWALLOWTAIL (NCT04740476) and LONGWING (ISRCTN12811235), respectively.
The MONARCH and ADMIRAL studies collectively enrolled more than 80 children with Dravet syndrome, ages 2 to 18, and results suggested that zorevunersen treatment reduced seizure frequency. Long-term findings from SWALLOWTAIL and LONGWING have consistently indicated the therapy’s efficacy in lowering seizure frequency, with some patients also displaying improvements in measures of cognition and behavior.
“The reductions in seizures in patients already receiving standard of care medicines, together with the improvements in multiple measures of cognition and behavior, demonstrate the potential of zorevunersen as the first disease modifying medicine that addresses the underlying cause of Dravet syndrome,” said Priya Singhal, MD, head of development at Biogen.
Stoke recently announced plans for a Phase 3 clinical trial called EMPEROR, which will test zorevunersen against a sham treatment in about 150 Dravet patients ages 2 through 17. The study is designed to be pivotal, meaning that positive results may support applications seeking zorevunersen’s approval. The Phase 3 study is expected to begin before the close of June, with results possible in late 2027.
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