Describe the rationale and design of a registrational clinical trial with BHV-7000 in idiopathic generalized epilepsy (IGE) with generalized tonic-clonic (GTC) seizures.

Epilepsy studies are traditionally placebo-controlled, change-from-baseline endpoint studies; participants receiving placebo for a fixed duration remain at risk for continued seizures, injury, and sudden unexpected death in epilepsy (SUDEP). We designed an innovative clinical trial that reduces these risks by utilizing a time to event (TTE) endpoint (Vossler 2020). BHV-7000 is a small molecule, selective activator of Kv7.2/7.3 potassium channels, in late-stage clinical development for epilepsy and neuropsychiatric disorders. In phase 1 studies, BHV-7000 was safe and well tolerated without CNS adverse effects typical of ASMs, such as somnolence.

SHINE is a Phase 2/3 randomized, double-blind, placebo-controlled study (NCT06425159), with an open-label extension (OLE), to evaluate the efficacy and safety of BHV-7000 in people with IGE with GTC seizures. Adults aged 18-75 years receiving 1-3 ASMs are eligible. Participants must have drug resistant epilepsy defined as failure of adequate trials of 2 tolerated and appropriately chosen ASM schedules. Approximately 242 participants will be randomized 1:1 to BHV-7000 75 mg or placebo once daily and treated for up to 24 weeks.

SHINE is currently ongoing. An FDA-endorsed time-to-event (TTE) primary endpoint is utilized; participants end double-blind treatment early if/when they have the protocol-defined seizure event of a second day with a GTC seizure and may enter the optional OLE phase. A key secondary endpoint is the proportion of participants with GTC seizure freedom during the double-blind phase, estimated using Kaplan-Meier methods. Safety and tolerability are also assessed.

SHINE is an innovative registrational study in IGE with the differentiated Kv7 activator BHV-7000. This patient-centric study utilizes a TTE endpoint that decreases time on placebo, potentially reducing the risk of exposure to additional seizures, injury, and SUDEP.