bexicaserin (LP352) / Lundbeck - LARVOL DELTA

A Phase 3, Placebo-Controlled Study to Investigate LP352 in Children and Adults With Dravet Syndrome (DS) (clinicaltrials.gov) - P3 | N=96 | Active, not recruiting | Sponsor: Longboard Pharmaceuticals | Trial completion date: Oct 2026 ➔ Dec 2026 | Trial primary completion date: Aug 2026 ➔ Dec 2026 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

A Phase 3, Placebo-Controlled Study to Investigate LP352 in Children and Adults With Dravet Syndrome (DS) (clinicaltrials.gov) - P3 | N=104 | Recruiting | Sponsor: Longboard Pharmaceuticals | N=160 ➔ 104

Enrollment change • CNS Disorders • Epilepsy

A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE) (clinicaltrials.gov) - P3 | N=292 | Active, not recruiting | Sponsor: Longboard Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Epilepsy

A Phase 3, Placebo-Controlled Study to Investigate LP352 in Children and Adults With Dravet Syndrome (DS) (clinicaltrials.gov) - P3 | N=30 | Sponsor: Longboard Pharmaceuticals | N=10 ➔ 30

Enrollment change • CNS Disorders • Epilepsy

Development and Validation of an LC-MS/MS Method for the Quantitative Estimation of Bexicaserin in Human Cerebrospinal Fluid. (PubMed, Biomed Chromatogr) - "Stability studies showed that bexicaserin was stable on bench for 24 h, in autosampler for over 50 h, and extract stability at 6°C for 76 h. Bexicaserin was stable after five freeze-thaw cycles and long-term storage at -20°C for 108 days and -80°C for 102 days."

Journal • CNS Disorders • Epilepsy

Effects of Bexicaserin on Neural Circuits in the DBA/1 Mouse Model of Sudden Unexpected Death in Epilepsy (SUDEP) (AES 2025) - "Bexicaserin (LP352), a potent and highly selective 5-HT2C receptor superagonist, is an investigational drug currently in development for the treatment of seizures in patients with DEEs... The efficacy of bexicaserin in reducing seizures and respiratory arrest in the DBA/1 mouse model of SUDEP is synonymous with its region-specific effects on brain activity. These data provide insights into the mechanisms underlying audiogenic seizures and seizure-induced respiratory arrest and the systems-level effects of bexicaserin resulting in reductions in seizures and SUDEP."

Preclinical • CNS Disorders • Epilepsy • FOS

Lundbeck's bexicaserin receives Breakthrough Therapy Designation in China for the treatment of seizures in severe rare epilepsies (The Manila Times) - "The medicine has also been granted BTD by the U.S. Food and Drug Administration (FDA) for the treatment of seizures associated with DEEs."

Breakthrough therapy • Epilepsy

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Ascending Doses and Dose Titration of Bexicaserin in Healthy Participants in a Randomized, Double-Blind, Placebo-Controlled Study. (PubMed, Clin Pharmacol Drug Dev) - "Bexicaserin (LP352) is a selective superagonist of the 5-hydroxytryptamine 2C (5-HT2C) receptor currently in development for the treatment of seizures that arise from developmental and epileptic encephalopathies...Overall, this Phase 1 MAD study demonstrated bexicaserin to be safe and well-tolerated, with rapid absorption, presence of one major metabolite, accumulation upon multiple dosing TID, and a greater than dose-proportional increase in exposures. These findings support the continued development of bexicaserin, which is currently in Phase 3 clinical trials."

Clinical • Journal • PK/PD data • CNS Disorders • Epilepsy

Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Food Effect of Bexicaserin in Healthy Participants: A First-in-Human Randomized, Double-Blind, Placebo-Controlled Single Ascending Dose Escalation Phase 1 Study. (PubMed, Clin Pharmacol Drug Dev) - "Bexicaserin (LP352) is a selective 5-hydroxytryptamine 2C (5-HT2C) superagonist in development for the treatment of seizures in developmental and epileptic encephalopathies (DEEs)...Increases in prolactin concentrations, a potential PD marker, were dose-dependent, suggesting central 5-HT2C receptor engagement. In summary, this Phase 1 SAD study demonstrated safety, tolerability, and adequate characterization of PK/PD of bexicaserin, which is currently in Phase 3 clinical development."

Clinical • Journal • P1 data • PK/PD data • CNS Disorders • Epilepsy

A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE) (clinicaltrials.gov) - P3 | N=324 | Enrolling by invitation | Sponsor: Longboard Pharmaceuticals | Recruiting ➔ Enrolling by invitation

Enrollment status • CNS Disorders • Epilepsy

Diazepine Agonists of the 5-HT2C Receptor with Unprecedented Selectivity: Discovery of Bexicaserin (LP352). (PubMed, J Med Chem) - "(+)-19m demonstrated excellent selectivity for 5-HT2CR over 5-HT2AR and 5-HT2BR and maximal activity exceeding that induced by the endogenous ligand 5-HT. (+)-19m has since progressed into clinical development."

Journal

Lundbeck to present positive pipeline data at American Academy of Neurology (AAN) Annual Meeting (PRNewswire) - P1b/2a | N=41 | PACIFIC OLE (NCT05626634) | Sponsor: Longboard Pharmaceuticals | "The data includes an oral presentation of the six-month results from the open-label extension (OLE) of the Phase 1b/2a PACIFIC trial of bexicaserin, a novel treatment under development for seizures associated with Developmental and Epileptic Encephalopathies (DEEs)....All bexicaserin treatment-naive patients (n=9) successfully transitioned from placebo to bexicaserin, reinforcing the tolerability of bexicaserin in an inclusive DEE population. In this placebo-bexicaserin switch population, a 57.3% reduction in countable motor seizures and 61.2% reduction in total seizures was observed, consistent with the response in non-naive participants at 6 months (n=32). Moreover, more than half of patients newly exposed to bexicaserin (n=5/9) experienced a ≥50% reduction from baseline in countable motor seizures."

P1/2 data • Epilepsy

A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE) (clinicaltrials.gov) - P3 | N=324 | Recruiting | Sponsor: Longboard Pharmaceuticals

New P3 trial • CNS Disorders • Epilepsy

A Sensitive and Selective LC-MS/MS-ESI Method for the Quantitation of Metabolites M9, M12, and M20 of Bexicaserin in Human Plasma and Urine Matrices. (PubMed, Biomed Chromatogr) - "Stability studies in plasma and urine showed that analytes were stable at bench-top for > 23.5 h and in autosampler for > 69 h. Analytes were stable after five freeze-thaw cycles and > 552 days of long-term storage at -20°C and -80°C."

Journal • CNS Disorders • Epilepsy

Lundbeck reached record revenue of DKK 22 billion in 2024 with accelerated growth for strategic brands (+21% CER) (Cision) - "The revenue of Lundbeck’s strategic brands increased by +21% CER (+20% DKK), reaching DKK 16,462 million, representing 75% of total revenue and with all four products showing double-digit growth rates both CER and reported: Rexulti: DKK 5,202 million (+16% CER; +15% DKK); Brintellix/Trintellix: DKK 4,847 million (+14% CER; +12% DKK)...Vyepti: DKK 2,909 million (+72% CER; +71% DKK)....For 2025, revenue growth is expected to be +7% to +10% at CER when compared to revenue of the prior year. The growth reflects especially the strong contribution from Vyepti, Rexulti in the U.S. and Brintellix in Europe. Lundbeck expects adjusted EBITDA growth to be 5% to 11% at CER when compared to adjusted EBITDA of the prior year, driven by the growth in revenue, partially offset by higher R&D investments. The significant increase in R&D costs driven by the phase III investment for bexicaserin and the further maturing of Lundbeck’s R&D pipeline..."

Commercial • CNS Disorders • Major Depressive Disorder • Migraine

Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy (clinicaltrials.gov) - P2 | N=41 | Completed | Sponsor: Longboard Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Epilepsy

Lundbeck announces positive results from 12-month Open-Label Extension (OLE) of the PACIFIC trial evaluating bexicaserin in participants with Developmental and Epileptic Encephalopathies (PRNewswire) - P2 | N=41 | PACIFIC OLE (NCT05626634) | Sponsor: Longboard Pharmaceuticals | "H. Lundbeck A/S (Lundbeck) announced positive results from the 12-month open-label extension of the Phase 1b/2a PACIFIC trial, evaluating bexicaserin in participants aged 12-65 with Developmental and Epileptic Encephalopathies (DEEs)....The PACIFIC OLE study is a 52-week Phase 2, open-label, long-term safety study of bexicaserin in participants with a range of DEEs including Dravet syndrome (n=3), Lennox-Gastaut syndrome (n=20) and DEE Other (n=18), who completed the PACIFIC trial (n=41)....The full results are expected to be presented at an upcoming medical conference in 2025....The median change in countable motor seizure frequency for participants in the OLE study over an approximate 12-month treatment period was a decrease of 59.3% (n=40) from their baseline entering the PACIFIC OLE study."

P2 data • CNS Disorders • Epilepsy

A Highly Sensitive Triple Quad LC-MS/MS Method Development and Validation for the Determination of Bexicaserin (LP352) in Human Plasma and Urine Matrices. (PubMed, Biomed Chromatogr) - "Stability studies in plasma and urine showed that bexicaserin was stable on bench for 24 h, in autosampler over 54 h, five freeze-thaw cycles, and long-term storage at -20°C and -80°C for > 368 days. The validated methods were successfully applied in clinical study."

Journal • CNS Disorders • Epilepsy

Bexicaserin has Negligible Drug-Drug Interaction Potential with Frequently Used Antiseizure Medications in a Phase 1b/2a Study in Participants with Developmental and Epileptic Encephalopathies (AES 2024) - P1/2 | " PACIFIC (LP352-201, NCT05364021) was a Phase 1b/2a study which enrolled patients taking stable doses of 1 – 4 concomitant ASMs... The data demonstrated no apparent clinically meaningful effect of bexciaserin on the pharmacokinetics of co-administered ASMs in this study; concentrations remained stable across all visits. Drug-drug interaction (perpetrator) potential was low for bexicaserin when co-administered with ASMs commonly used by PACIFIC study participants. In the treatment of patients with DEEs in the PACIFIC study, bexicaserin appeared to be safely added to patients' ASM regimens, regardless of the concomitant ASM(s) or dose."

P1/2 data • CNS Disorders • Epilepsy

Bexicaserin Demonstrates Similar Reduction of Countable Motor Seizures in Adolescents and Adults with Developmental and Epileptic Encephalopathies: Analysis of the Phase 1b/2a PACIFIC Study (AES 2024) - P1/2 | "Rationale: The PACIFIC study (LP352-201, NCT05364021), which enrolled participants 12-65 years of age, showed meaningful reduction in countable motor seizures (CMS; 59.8% in bexicaserin versus 17.4% in placebo groups), and a favorable safety profile... In this post-hoc analysis, adolescent and adult participants with DEEs achieved similar reductions of CMS frequency during treatment with bexicaserin compared to baseline. Both age groups demonstrated substantial reductions of CMS frequency that were comparable to previously reported aggregate data. These results provide support for the inclusion of younger participants in future Phase 3 studies of bexicaserin for the treatment of seizures in DEEs, which typically emerge during the first few years of life."

Clinical • P1/2 data • CNS Disorders • Epilepsy

Bexicaserin Reduces Seizures and Respiratory Arrest in a Mouse Model of SUDEP (AES 2024) - P1/2 | "Bexicaserin (also known as LP352), a potent and highly selective 5-HT2C receptor superagonist, is currently in development for the treatment of seizures in patients with DEEs... Bexicaserin significantly reduced seizures and respiratory arrest in a mouse model of SUDEP. Given the risk of SUDEP in patients with DEEs and the demonstrated efficacy of bexicaserin in reducing seizures in participants with various DEEs from the PACIFIC study, these data support the potential of bexicaserin to mitigate SUDEP risk in this patient population."

Preclinical • CNS Disorders • Epilepsy

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 (AES 2024) - P1/2 | "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. 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)... 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."

Clinical • CNS Disorders • Epilepsy

A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE) (clinicaltrials.gov) - P3 | N=320 | Recruiting | Sponsor: Longboard Pharmaceuticals

New P3 trial • CNS Disorders • Epilepsy

A Phase 3, Placebo-Controlled Study to Investigate LP352 in Children and Adults with Dravet Syndrome (DS) (clinicaltrials.gov) - P3 | N=160 | Recruiting | Sponsor: Longboard Pharmaceuticals

New P3 trial • CNS Disorders • Epilepsy

Progress report on new medications for seizures and epilepsy: A summary of the 17th Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVII). II. Drugs in more advanced clinical development. (PubMed, Epilepsia) - "These investigational treatments include azetukalner (XEN1101), a potent, KV7.2/7.3-specific potassium channel opener in development for the treatment of focal seizures, generalized tonic-clonic seizures, and major depressive disorder; bexicaserin (LP352), a selective 5-HT2C receptor superagonist in development for the treatment of seizures associated with developmental and epileptic encephalopathies; radiprodil, a selective negative allosteric modulator of NR2B subunit-containing N-methyl-D-aspartate glutamate receptors, in development for the treatment of seizures and behavior manifestations associated with disorders caused by gain-of-function mutations in the GRIN1, -2A, -2B, or -2D genes; soticlestat (TAK-935), a selective inhibitor of cholesterol 24-hydroxylase in development for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome; and STK-001, an antisense oligonucleotide designed to upregulate Nav1.1 protein expression and improve..."

Journal • Metastases • CNS Disorders • Depression • Epilepsy • Major Depressive Disorder • Mood Disorders • Psychiatry • NAV1