Bexicaserin Produces Significant Seizure Reduction in PACIFIC OLE Trial for Developmental and Epileptic Encephalopathies
The 12-month open-label extension of the PACIFIC trial demonstrated that bexicaserin significantly reduced seizure frequency in patients with developmental and epileptic encephalopathies while maintaining a favorable safety and tolerability profile.
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Findings from a 12-month open-label extension (OLE) of the Phase Ib/IIa PACIFIC trial demonstrated patients with developmental and epileptic encephalopathies (DEEs) treated with bexicaserin experienced a significant reduction in seizure frequency with a tolerable safety profile.1 Bexicaserin, a 5-HT2C receptor agonist, was originally developed by Longboard Pharmaceuticals, which was acquired by H. Lundbeck A/S in October 2024.2
“We are very pleased to observe a longer-term sustainable response, along with a favorable safety and tolerability profile over a 12-month period. These results further reinforce our confidence in bexicaserin’s unique and potentially best-in-class profile. Considering the significant unmet needs of patients with DEEs, we are encouraged by the long-term sustainability of bexicaserin treatment,” Johan Luthman, executive vice president and head of Research & Development at Lundbeck, said in a press release.1
In June 2024, Longboard announced positive interim findings from the OLE of the PACIFIC trial in 41 patients aged 12-65 years with DEEs who completed the PACIFIC trial. These DEEs included Dravet syndrome (n=3), Lennox-Gastaut syndrome (n=20), and other (n=18).
Trial Design
PACIFIC OLE is a 52-week open-label, long-term safety trial conducted at 34 sites across the United States and Australia to evaluate the safety and tolerability of multiple doses of bexicaserin in patients with DEEs. The trial consisted of a five-week screening period and baseline evaluations. Patients were given a dose titration for a 15-day period before continuing on maximum-tolerated dose for a maintenance period of 60 days. After this period, patients titrated down and those who were eligible were allowed to enroll in the 52-week OLE. In total, 100% of those completing the PACIFIC trial chose to enroll in the OLE, of whom 92.7% stayed for the duration of the 12-month OLE period.
Investigators are also evaluating the efficacy of bexicaserin on the frequency of observed countable motor seizures and other seizure types. The OLE evaluation was initiated at approximately 12-months into the extension study. Lundbeck stated that it anticipates releasing full data from the OLE at an upcoming medical conference in 2025.
Results released to date across an approximately 12-month treatment period among patients in the OLE show the median change in countable motor seizure frequency decreased by 59.3% (n=40) from baseline entering the OLE.
Median change in countable motor seizure frequency from baseline for patients who were randomly assigned to receive bexicaserin in the PACIFIC trial and who continued into the 12 month OLE was a reduction of 60.4% (n=31). Further, patients randomly assigned to receive a placebo in the PACIFIC trial who transitioned to bexicaserin in the 12-month OLE had a median change in countable motor seizure frequency that was a reduction of 58.2% (n=9).
In terms of safety, treatment-emergent adverse events (TRAEs) were reported in >5% of those in the overall group (n=41). The most frequently reported TRAEs included upper respiratory tract infections; seizures; COVID-19; reduced appetite; lethargy; pyrexia; gait disturbance; gastroenteritis viral; pneumonia; sinusitis; vomiting; weight loss; and rash. One patient discontinued treatment because of lethargy, one withdrew content, and one discontinued because of relocation.
Bexicaserin is also currently under evaluation in the Phase III DEEp SEA trial to treat seizures associated with Dravet syndrome in patients aged two years and older.3
References
1. Lundbeck announces positive results from 12-month Open-Label Extension (OLE) of the PACIFIC trial evaluating bexicaserin in participants with Developmental and Epileptic Encephalopathies. News release. H. Lundbeck A/S. January 30, 2025. Accessed January 31, 2025. https://www.lundbeck.com/us/newsroom/2025/lundbeck-announces-positive-results-from-12-month-open-label-ext
2. Lundbeck to acquire Longboard Pharmaceuticals in a strategic deal, significantly enhancing its neuroscience pipeline. Lundbeck. October 14, 2024. Accessed January 31, 2025. https://www.newsroom.lundbeckus.com/news-release/2024/lundbeck-to-acquire-longboard-pharmaceuticals-in-a-strategic-dea
3. Longboard Pharmaceuticals Initiates Phase 3 DEEp SEA Study Evaluating Bexicaserin in Dravet Syndrome. News release. Longboard Pharmaceuticals. September 26, 2024. Accessed January 31, 2025. https://www.businesswire.com/news/home/20240926926536/en/Longboard-Pharmaceuticals-Initiates-Phase-3-DEEp-SEA-Study-Evaluating-Bexicaserin-in-Dravet-Syndrome
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