Skyline Study to Test Soticlestat Safety, Efficacy in Patients Ages 2–21

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by Mary Chapman |

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A Phase 3 clinical trial is recruiting Dravet syndrome patients between the ages of 2 and 21 to assess the effectiveness, safety, and tolerability of the investigational treatment soticlestat when taken with other anti-seizure therapies.

Called the Skyline study, the trial (NCT04940624) will test soticlestat as an add-on therapy for Dravet patients who have had at least four convulsive seizures monthly for the previous six weeks, and who have been unable to control seizures with at least two anti-seizure medications.

Prolonged, treatment-resistant seizures — frequent episodes of uncontrolled electrical activity between brain cells — are a hallmark of Dravet syndrome. Such seizures, which can be caused by increases in body temperature as well as by other triggers, are highly resistant to currently available therapies.

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Soticlestat, developed by Takeda Pharmaceuticals in partnership with Ovid Therapeutics, has been found to provide protection against seizures triggered by fever in animal studies.

Now, Takeda is sponsoring a multicenter, placebo-controlled, global trial to test the therapy in children and young adults. The Skyline study will take place in 74 locations, including the United States, Australia, Canada, China, Japan, and the Russian Federation, as well as in several European Union countries.

It seeks to enroll about 142 Dravet patients, is expected to last between 22 and 25 weeks (about four to five months), and will involve up to five planned in-person visits.

The total daily dose of soticlestat will be based on body weight during the four-week titration period, which will determine the dose a person can tolerate. During that time, participants will receive soticlestat or placebo at increased doses, barring tolerability issues. Participants who cannot tolerate the minimum dose will be dropped from the study.

After the titration period, participants will continue to receive the same dosage they were given at its end, which will continue for a 12-week maintenance period. Following Skyline’s completion, participants will have the option of joining an open-label extension (OLE) study in which all will receive soticlestat. Those who won’t be joining the OLE study will have their treatment tapered off over one week and will complete a safety follow-up visit or phone call about two weeks after their last dose of the experimental treatment.

Soticlestat is a powerful, highly selective, first-in-class inhibitor of cholesterol 24-hydroxylase (CH24H). CH24H expedites the clearance of cholesterol from the brain. The treatment also contributes to the regulation of glutamate, a chemical messenger that, at excessive levels, can promote seizures. Because such CH24H levels can activate glutamate signaling pathways, inhibiting CH24H with the treatment candidate could lower the frequency and severity of seizures.

A study by scientists in the U.S. and Japan found that treatment with soticlestat provided protection against fever-induced seizures in two mouse models of Dravet. Also, soticlestat was found to be safe and effective in clinical trials, including the global, Phase 2 ELEKTRA study (NCT03650452) for lessening seizure frequency in pediatric Dravet patients.

Takeda Pharmaceuticals acquired the global rights to develop and market the treatment in May 2021. The therapy was granted orphan drug status by the U.S. Food and Drug Administration in 2017, for Dravet and the rare epilepsy Lennox-Gastaut.

Another global Phase 3 clinical trial also is studying soticlestat and recruiting Dravet patients, ages 2–36. That trial, also sponsored by Takeda, launched in March and will run through 2025.