Authors :
Presenting Author: Ngoc Minh Le, MD – Longboard Pharmaceuticals, Inc.
Sheila Smith, DNP – Longboard Pharmaceuticals, Inc.
Morgan Weberg, BS – Longboard Pharmaceuticals, Inc.
Shikha Polega, PharmD – Longboard Pharmaceuticals, Inc.
Rationale:
Developmental and epileptic encephalopathies (DEEs) are the most severe group of epilepsies characterized by drug-resistant seizures, EEG epileptiform abnormalities, and developmental plateauing or regression. DEE trials have historically focused on specific epilepsy syndromes such as Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS). Bexicaserin is a highly selective 5-HT2C receptor superagonist that demonstrated a favorable safety and tolerability profile in the Phase 1b/2a PACIFIC study in participants with DS, LGS, and other DEEs. Efficacy as assessed by seizure reduction was similar in all subgroups, including LGS and DEE Other, which are highly etiologically heterogeneous. Here, we assess the long-term safety, tolerability, and efficacy of bexicaserin in a cohort of participants who were newly exposed to bexicaserin in the OLE.
Methods:
The PACIFIC open-label extension study investigated the safety, tolerability, and efficacy of bexicaserin for the treatment of seizures in participants aged ≥12 and ≤ 65 years of age with DS, LGS, and DEE Other. After completing the PACIFIC study, 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.
Results:
Forty-one participants (32 bexicaserin, 9 placebo) enrolled (20 LGS, 3 DS,18 DEE Other) in the OLE and received bexicaserin across 34 sites. In this interim analysis, the cohort of 9 randomized to placebo in the PACIFIC study enrolled in the OLE, received bexicaserin, and then evaluated for safety, tolerability, and efficacy at approximately 6 months. All 9 participants were successfully titrated to their maximum tolerated dose and entered the maintenance phase of the OLE. The efficacy is consistent with that reported in the PACIFIC study, with no new serious adverse events (SAEs) reported. After receiving bexicaserin in the OLE, this cohort experienced a -57.3% reduction in countable motor seizures (CMS) and a -61.2% reduction in total seizures. Moreover, 55.6% of these participants demonstrated a ≥ 50% reduction in frequency of CMS.
Conclusions:
In the placebo cohort managed with standard-of-care antiseizure medication(s) during the double-blind PACIFIC study, the addition of bexicaserin demonstrated a sustained and favorable safety and efficacy profile consistent with that previously reported. All participants successfully transitioned from placebo to bexicaserin with no discontinuations, reinforcing bexicaserin’s tolerability in an all-inclusive DEE population. The comparable seizure reductions in the placebo-to-bexicaserin cohort noted in the OLE reinforce bexicaserin's consistency across heterogeneous DEE subgroups and are supportive of further Phase 3 development, as a potential treatment for patients with various types of DEEs.
Funding:
Longboard Pharmaceuticals, Inc sponsored this study.