To assess the long-term safety, tolerability, and efficacy of bexicaserin in participants newly exposed to bexicaserin.

Developmental and epileptic encephalopathies (DEEs) are the most severe group of epilepsies characterized by drug-resistant seizures, electroencephalogram background abnormalities, and developmental plateauing or regression. Bexicaserin is a highly specific and selective 5-HT_2C receptor superagonist that demonstrated a favorable safety, tolerability, and efficacy profile in the double-blind Phase 1b/2a PACIFIC study in participants with Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and other DEEs.

The open-label extension (OLE) of the PACIFIC study further investigated the safety, tolerability, and efficacy of bexicaserin for the treatment of seizures in participants aged ≥12 and ≤65 years with DS, LGS, and DEE Other. After completing PACIFIC, participants were given the option to enroll in the OLE. They underwent a 15-day flexible titration period (maximum dose of 12 mg TID, based on tolerability), followed by up to one year of maintenance treatment.

Forty-one participants (32 bexicaserin, 9 placebo) enrolled (3 DS, 20 LGS,18 DEE Other) in the OLE and received bexicaserin. All 9 placebo participants who then received bexicaserin in the OLE successfully titrated to their maximum tolerated dose and entered the OLE maintenance phase. In this interim analysis of the placebo-to-bexicaserin cohort, at approximately 6 months, no new serious adverse events were reported. Furthermore, a 57.3% reduction in countable motor seizures and a 61.2% reduction in total seizures were observed. Moreover, 55.6% of participants demonstrated a ≥50% reduction in countable motor seizure frequency.

All participants successfully transitioned from placebo to bexicaserin in the OLE with no discontinuations, reinforcing the tolerability of bexicaserin in an inclusive DEE population. The comparable seizure reductions in the double-blind PACIFIC study and the placebo-to-bexicaserin cohort in the OLE reinforce the consistency of bexicaserin across heterogeneous DEE subgroups and are supportive of Phase 3 development.