Clinical Insights on the Long-Term Efficacy, Safety Profile of Bexicaserin in Developmental Epileptic Encephalopathies: Johannes Streffer, MD

WATCH TIME: 4 minutes

"What stands out clinically is not only the rapid onset of seizure reduction, but also the fact that this effect is sustained for years without new safety concerns. That combination is extremely meaningful in a population living with high treatment burden."

Developmental and epileptic encephalopathies (DEEs) remain among the most treatment-resistant forms of epilepsy, often requiring complex polytherapy regimens with limited long-term seizure control and substantial safety considerations. This patient population was a major topic of conversation at the recently concluded 2025 American Epilepsy Society (AES) Annual Meeting, held December 5 to 9, 2025, in Atlanta, Georgia. At the meeting, investigators presented promising data from the expanded access program (EAP) of a phase 1/2 trial testing bexicaserin (Lundbeck), a highly selective superagonist of the 5-hydroxytryptamine type 2C (5-HT2C) receptor, in DEEs.

The large-scale EAP included patients with a diagnosis of either Dravet syndrome (DS; n = 3), Lennox-Gastaut syndrome (LGS; n = 14), or other DEE (n = 17) who completed the 12-month, double-blind PACIFIC trial (NCT05364021). All told, bexicaserin-treated patients recorded a median percentage change of –60.2 (n = 30) for countable motor seizures after 18 months of treatment (6-month EAP data cut) and median reductions of –53.7% at 24 months (12-month EAP data cut). Encouragingly, there were no new safety signals identified, with the most common treatment-emergent adverse events being upper respiratory tract infections, seizures, COVID-19, and decreased appetite, among others.

During the meeting, NeurologyLive^® caught up with Johannes Streffer, MD, senior vice president of clinical development at Lundbeck, to discuss the findings in greater detail. In this interview, Streffer reviewed the long-term efficacy and safety data presented at AES 2025, including sustained seizure reduction through 1 year of open-label treatment and emerging experience extending up to 48 months. He also outlined the drug’s selective 5-HT2C mechanism, minimal drug-drug interaction profile, and potential clinical advantages in highly medicated DEE populations.

Click here for more AES 2025 coverage.

REFERENCE
1. Sylvia C, Polega S, Knowles N, Kaye R, Loft H, Uz T. Bexicaserin for the treatment of seizures in developmental and epileptic encephalopathies: interim analysis of an expanded access program for participants on treatment for up to 2 years. Presented at: 2025 AES Annual Meeting; October 5-9; Atlanta, GA. Abstract 1.564.