Additional Efficacy Analyses of the Bexicaserin PACIFIC Study in Participants with Developmental and Epileptic Encephalopathies: Responder Rates, Number Needed to Treat, and Seizure-free Days
Abstract number :
1.402
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2024
Submission ID :
1066
Source :
www.aesnet.org
Presentation date :
12/7/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Terence J O'Brien, MBBS MD – School of Translational Medicine, Monash University, The Alfred Centre
Dennis Dlugos, MD – The Children’s Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, PA, USA
Chad Orevillo, MPH – Longboard Pharmaceuticals, Inc.
Dewey McLin, PhD – Longboard Pharmaceuticals, Inc.
Shikha Polega, PharmD – Longboard Pharmaceuticals, Inc.
Randall Kaye, MD – Longboard Pharmaceuticals, Inc.
Rationale: Bexicaserin is an oral, centrally acting, highly selective 5-HT2C receptor superagonist that demonstrated a favorable safety and tolerability profile in the Phase 1b/2a PACIFIC study in participants with Dravet Syndrome (DS), Lennox-Gastaut Syndrome (LGS), and other developmental and epileptic encephalopathies (DEEs). Treatment with bexicaserin showed meaningful reduction in countable motor seizures (CMS; 59.8% bexicaserin versus 17.4% placebo). Moreover, 60.0% of participants treated with bexicaserin experienced a ≥50% reduction in frequency of CMS versus 33.3% in those receiving placebo. Here we report the proportion of participants who experienced ≥75% reductions in CMS, the corresponding number needed to treat (NNT), and number of seizure-free days from the PACIFIC study.
Methods: Patients with DEEs (DS, LGS, or DEE Other) were eligible to enroll in the PACIFIC study (LP352-201, NCT05364021) if they were 12-65 years of age, experienced an average of ≥4 CMS per 28-days during the 12 weeks before screening, and were taking 1-4 concomitant anti-seizure medications (ASMs). Participants were randomly assigned (4:1) to receive bexicaserin (targeted highest dose of 12 mg three times daily [TID], based on tolerability) or placebo, in addition to their concomitant ASM regimen. Following a 15-day titration period, each participant’s maximum tolerated dose (6, 9, or 12 mg TID) was maintained for 60 days, and then tapered off over 5 to 15 days.
Results: Fifty-two participants were enrolled (29 LGS, 4 DS, and 19 DEE Other) and assigned to bexicaserin (n=43) or placebo (n=9) groups. Of these, 35/43 and 9/9, respectively, entered the maintenance period. The proportion of bexicaserin patients experiencing a ≥75% reduction in CMS during maintenance was 31.4% (n=11/35), versus none with placebo (n=0/9); the NNT to achieve a ≥75% reduction in CMS for these patients was 3.2. Overall, participants treated with bexicaserin experienced a median of 53 seizure-free days during the treatment period compared with 43 seizure-free days in those receiving placebo (standard-of-care), the difference reflecting 10 additional seizure-free days.
Conclusions: Bexicaserin demonstrated a positive benefit-risk profile in a broad DEE population in this trial. Treatment with bexicaserin demonstrated a clinically meaningful impact on participants, resulting in ≥75% reductions in CMS in approximately one-third of participants versus none who received placebo (standard-of-care). For approximately every 3 patients with a DEE treated with bexicaserin in the PACIFIC study maintenance phase, 1 patient achieved ≥75% reduction in CMS. Taken together, the relatively low NNT of 3.2 to achieve a ≥75% seizure reduction, and 10 additional seizure-free days throughout the treatment period is supportive of further Phase 3 development in this population, as a treatment for patients with DS, LGS and a variety of other DEEs.
Funding: This study was sponsored by Longboard Pharmaceuticals, Inc.
Anti-seizure Medications