Long-Term Expanded Access Program Data Support Phase 3 Development of Bexicaserin in Developmental Epileptic Encephalopathies

Newly presented findings from a phase 1/2 open-label expanded access program (EAP) showed that patients with developmental and epileptic encephalopathies (DEEs) experienced consistent, sustained reductions in countable motor seizure frequency for up to two years with investigational bexicaserin (Lundbeck). Alongside a favorable safety and tolerability profile, these results support continued advancement into a larger phase 3 program, currently underway as DEEp.¹

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). In the 12-month OLE, patients received a 6-mg starting dose of bexicaserin, a highly selective superagonist of the 5-hydroxytryptamine type 2C (5-HT2C) receptor, 3 times a day, including those who had received placebo in the randomized controlled trial (RCT) portion.

As of the data cutoff date (August 13, 2025) a total of 36 participants enrolled in the EAP, continuing their maintenance dosing regimen of bexicaserin from the OLE; of these participants, 34 remain in the EAP. Presented at the 2025 American Epilepsy Society (AES) Annual Meeting, held December 5-9 in Atlanta, Georgia, investigators 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).

"We are amazed to see this efficacy continued through the open-label extension for 1 year," Johannes Streffer, senior vice president of Clinical Development for Lundbeck, told NeurologyLive^® at the meeting. "In addition, despite the fact that this group has a lot of different antiseizure medications and is vulnerable, we did not identify any significant safety signal. These patients tolerate it very well, and seemingly, patients and families believe that this is the right choice for them, otherwise they would have not stuck with us for another year."

At 18 months of bexicaserin treatment (6-month EAP data cut), median reductions in countable motor seizure frequency from the RCT baseline were –73.0% in DS (n = 3), –51.9% in LGS (n = 12), and –61.5% in other DEEs (n = 15). By 24 months (12-month EAP cut), these reductions were –100% in DS (n = 1), –37.1% in LGS (n = 6), and –73.7% in DEE Other (n = 10). These longer-term findings are consistent with earlier cumulative data from the OLE, which showed sustained reductions in countable motor seizures through one year: DS, –64.2% (n = 3); LGS, –44.2% (n = 19); DEE Other, –79.5% (n = 18). They also aligned with the outcomes seen in the original RCT, where reductions were –74.6% in DS (n = 3), –50.8% in LGS (n = 17), and –65.5% in DEE Other (n = 15).

Streffer added, "Bexicaserin is a highly selective drug. Whereas many therapies act on multiple receptors and lack specificity, bexicaserin is a very selective 5-HT2C–targeting agent. This mechanism provides a clear rationale for its antiseizure effects, and we believe its favorable safety profile is partly due to this selectivity. Because of the drug’s unique metabolism, we’ve also observed very minimal drug–drug interactions."

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Throughout the OLE, no new safety signals were identified, with most common treatment-emergent adverse events (TEAEs) being upper respiratory tract infections, seizures, COVID-19, decreased appetite, lethargy, pyrexia, gait disturbance, gastroenteritis viral, pneumonia, sinusitis, vomiting, weight decreased, and rash. Overall, 8 of 41 participants (19.5%) experienced 11 serious TEAEs—including seizures (n = 4), pneumonia (n = 3), bacterial pneumonia (n = 1), gait disturbance (n = 1), small intestine obstruction (n = 1), and agitation (n = 1)—and in the EAP, 1 participant had an SAE of death that was deemed unrelated to the study drug.

"This was the first time we were able to study a treatment across this full spectrum (of DEEs), but it required very careful consideration," Streffer continued. "Defining who could enter the trial was a major task, and we worked closely with scientific and academic leaders to establish clear, rigorous inclusion criteria. That collaboration has been essential as we now move this program forward into Phase 3."

The ongoing phase 3 DEEp program, initiated in late 2024, includes 2 phase 3 studies, dubbed DEEp SEA, which focuses on DS only, and DEEp OCEAN, which is centered around those with LGS and other DEEs. Both trials are global, double-blind, placebo-controlled studies that include a screening period, titration phase, maintenance period, and open-label extension. DEEp SEA and DEEp OCEAN, which are expected to include 160 and 320 participants, respectively, will use change in countable motor seizures as the primary end point, with other secondary objectives that focus on safety and tolerability of bexicaserin.^2,3

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REFERENCES
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, Georgia. ABSTRACT 1.564.
2. A Phase 3, Placebo-Controlled Study to Investigate LP352 in Children and Adults With Dravet Syndrome (DS). Clinicaltrials.gov. Updated November 17, 2025. Accessed December 9, 2025. https://www.clinicaltrials.gov/study/NCT06660394
3. Longboard Pharmaceuticals Initiates Phase 3 DEEp OCEAN Study Evaluating Bexicaserin in Developmental and Epileptic Encephalopathies (DEEs). News release. Longboard Pharmaceuticals. November 12, 2024. Accessed December 9, 2025. https://www.businesswire.com/news/home/20241112523128/en/Longboard-Pharmaceuticals-Initiates-Phase-3-DEEp-OCEAN-Study-Evaluating-Bexicaserin-in-Developmental-and-Epileptic-Encephalopathies-DEEs