Tomson, Torbjörn

Abstract This article summarizes data for 13 investigational treatments for which at least preliminary seizure outcome data in patients with epilepsy were reported at the Eighteenth Eilat Conference on New Antiepileptic Drugs and Devices held in Madrid, Spain, on May 3–6, 2026. The treatments reviewed include bexicaserin, a selective 5‐hydroxytryptamine (5‐HT, serotonin) type 2C (5‐HT 2C ) receptor superagonist investigated as a treatment for developmental and epileptic encephalopathies (DEEs); BMB‐101, a selective 5‐HT 2C receptor agonist investigated for the treatment of absence seizures and DEEs; elsunersen, an antisense oligonucleotide designed for the treatment of early‐onset SCN2A ‐DEE; EPX‐100 (clemizole hydrochloride), an antihistamine endowed with agonist activity at 5‐HT 2A and 5‐HT 2B receptors, repurposed as a treatment for DEEs; ES‐481, an antagonist of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors containing the transmembrane AMPA receptor regulatory protein γ8 (TARP‐γ8), under investigation for the treatment of drug‐resistant epilepsy; ETX‐101, a gene therapy in development for the treatment of SCN1A ‐positive Dravet syndrome; PrevEp‐006 (intranasal seletracetam), a synaptic vesicle glycoprotein 2A (SV2A) ligand under investigation as an acute seizure rescue therapy; radiprodil, a negative allosteric modulator that binds to the GluN2B subunit of the N ‐methyl‐ D ‐aspartate (NMDA) receptor, in development for the treatment of seizures and other symptoms associated with GRIN‐related neurodevelopmental disorder, tuberous sclerosis complex, and focal cortical dysplasia type II; RAP‐219, a selective negative allosteric modulator of TARP‐γ8, in development for drug‐resistant focal epilepsy; relutrigine, a selective disease‐state sodium channel modulator investigated as a treatment for SCN2A ‐ and SCN8A ‐DEE; Staccato Alprazolam, a breath‐actuated device that delivers alprazolam to the lungs for rapid seizure termination; vormatrigine, a functionally selective sodium channel modulator in development for the treatment of focal seizures; and zorevunersen, an antisense oligonucleotide engineered to restore endogenous Nav1.1 protein expression, investigated for the treatment of Dravet syndrome. Overall, the evidence reviewed justifies expectations for improved health outcomes for the millions of children and adults with epilepsy who do not fully benefit from existing therapies.

Abstract Over the last 34 years, the Eilat Conference on New Antiepileptic Drugs and Devices has provided an interactive forum for stakeholders to discuss investigational and recently licensed treatments for seizures and epilepsy. The Eighteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVIII) took place in Madrid, Spain, on May 3–6, 2026. This article provides summaries of eight treatments in preclinical and early clinical development that were presented at EILAT XVIII. These include AUT00206, a positive allosteric modulator of Kv3.1 and Kv3.2 voltage‐gated potassium channels in development for the treatment of rare epilepsy syndromes as well as neurodevelopmental and neuropsychiatric disorders; ION283, an antisense oligonucleotide designed to suppress the expression of glycogen synthase 1, under investigation for the treatment of Lafora disease; MSCA‐7136, a selective allosteric RAS/mitogen‐activated protein kinase—extracellular signal regulated kinase (MEK) inhibitor being developed for the treatment of focal seizures associated with mesial temporal lobe epilepsy and seizures associated with tuberous sclerosis complex; OV329, a selective inhibitor of γ‐aminobutyric acid (GABA) aminotransferase, in development for the treatment of drug‐resistant focal seizures; PTI5803 (probenecid), an uricosuric agent and a blocker of pannexin 1 channels, repurposed as a treatment for seizures associated with focal cortical dysplasia; simufilam, a filamin A modulator under investigation for the treatment of tuberous sclerosis complex‐related epilepsy; SN‐2000, a selective allosteric phosphodiesterase 4B inhibitor, in development for the treatment of focal seizures; and sodium selenate, a promoter of the dephosphorylation of pathological hyperphosphorylated tau in the brain, under investigation as a disease‐modifying agent in mesial temporal lobe epilepsy. Treatments in more advanced clinical development are discussed in an accompanying article.