Stoke's Dravet syndrome med released from partial clinical hold as company eyes phase 3 plans

Stoke Therapeutics’ Dravet syndrome drug has been freed from a partial hold, clearing the way for the construction of a phase 3 program.

While studies for STK-001, now known as zorevunersen, had continued on for certain doses, Stoke can now test multiple doses above 45 mg.

“We thank the FDA for working with us to remove the partial clinical hold and look forward to continuing our discussions with them and with other global regulatory agencies toward the goal of agreeing on a single, global phase 3 registrational study design by year-end,” said CEO Edward Kaye, M.D., in a Wednesday statement that accompanied second-quarter earnings. 

Dravet syndrome is a rare genetic form of epilepsy that occurs in infancy typically triggered by hot temperatures or fever. The lifelong condition leads to frequent seizures, delayed language and speech issues, behavioral and developmental delays and other challenges.

Zorevunersen’s journey through the clinic so far has been a bit of a roller coaster ride. The therapy was being evaluated in two phase 1/2a studies and an open-label extension study in children and adolescents with Dravet syndrome. The FDA placed the partial clinical hold on one of the studies called MONARCH but allowed a 70-mg dose to be tested.

Just over a year ago, Stoke’s shares were sent tumbling when the therapy spurred adverse events in a third of patients during the midstage trial, despite otherwise positive data touted by the company showing reductions in convulsive seizure frequency. The most common adverse events were CSF protein elevations, vomiting and irritability.

But then, in March of this year, Stoke’s shares yo-yoed on the news that phase 1/2a data showed a median 43% reduction in frequency of convulsive seizures in patients with the seizure disorder aged 2 and 18 years. Those data allowed the company to meet with the FDA to start planning the phase 3 trial.

And now, with the clinical hold out of the way, the path is fully clear for the late-stage test that could bring Stoke within the grasp of an FDA application, should data be positive.

Meanwhile, Stoke will be taking the data collected so far on the road, presenting existing data at the European Epilepsy Congress in September.