Progress report on new antiepileptic drugs: A summary of the Fourteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIV). I. Drugs in preclinical and early clinical development

Abstract

Summary The Fourteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIV) took place in Madrid, Spain, on May 13‐16, 2018 and was attended by 168 delegates from 28 countries. The conference provided a forum for professionals involved in basic science, clinical research, regulatory affairs, and clinical care to meet and discuss the latest advances related to discovery and development of drugs and devices aimed at improving the management of people with epilepsy. This progress report provides a summary of findings on investigational compounds for which data from preclinical or early (phase I) clinical studies were presented. The compounds reviewed include adenosine and adenosine kinase inhibitors, BIS‐001 (huperzine A), 2‐deoxy‐d‐glucose, FV‐082, FV‐137, JNJ‐40411813, JNJ‐55511118 and analogs, ketone‐enhanced antiepileptic drugs, oxynytones, OV329, TAK‐935 (OV935), XEN901, and XEN1101. Many innovative approaches to drug development were presented. For example, some compounds are being combined with traditional antiepileptic drugs based on evidence of synergism in seizure models, some act as inhibitors of enzymes involved in modulation of neuronal activity, and some interact in novel ways with excitatory receptors or ion channels. Some of the compounds in development target the etiology of specific epilepsy syndromes (including orphan conditions) through precision medicine, and some offer hope of producing disease‐modifying effects rather than symptomatic seizure suppression. Overall, the results summarized in the report indicate that important advances are being made in the effort to develop compounds with potentially improved efficacy and safety profiles compared with existing agents.

Progress report on new antiepileptic drugs: A summary of the Fourteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIV). II. Drugs in more advanced clinical development

“…Review of the data presented at the EILAT XIV Conference, summarized in this report and in an accompanying article, indicates that major efforts in preclinical and clinical research are continuing in order to develop novel AEDs. The overarching aim is to discover treatments with superior efficacy and safety compared with existing agents, especially for the management of patients with difficult to treat epilepsies.…”

“…The Fourteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIV) took place in Madrid, Spain, on May 13‐16, 2018 and was attended by 168 delegates from 28 countries. As explained in some detail in an accompanying report, the conference allowed professionals actively engaged in basic science, clinical research, regulatory affairs, and clinical care to meet and discuss key topics related to antiepileptic drug (AED) discovery and development. Additionally, the conference offered the opportunity to review data on a number of novel agents that are currently being investigated as potential epilepsy treatments.…”

“…The accompanying report summarizes the latest findings for 12 different compounds (or classes of compounds) for which preclinical or early phase (phase I) clinical data were presented . The current report focuses on eight compounds/classes of compounds in more advanced clinical development, for which at least preliminary results from efficacy and safety studies conducted in patients were made available.…”

TMS as a pharmacodynamic indicator of cortical activity of a novel anti‐epileptic drug, XEN1101

“…XEN1101 is a novel positive allosteric modulator (“opener”) of the potassium channel KCNQ2/3 (Kv7.2/7.3) currently being developed by Xenon Pharmaceuticals Inc. for the treatment of focal epilepsy. Potentiating the open state of KCNQ2/3 channels favors a hyperpolarized resting state . This mechanism has been clinically proven effective for focal onset seizures using the KCNQ2/3 opener, retigabine …”

An evaluation of zonisamide, including its long-term efficacy, for the treatment of focal epilepsy

“…These drugs include cenobamate (blocks the persistent Na + -current in inactive sodium channels), ganaxolone and Sage-547 (analogues of allopregnanolone, an endogenous neurosteroid), padsevonil (3rd generation SV2A-modulator) and several repurposed compounds or derivatives of old compounds like everolimus, fenfluramine, valnoctamide and others. For a complete overview, see Golyala and Kwan (2017) or Bialer et al (2018) [13,14]. In addition, some already marketed AEDs are being studied in order to extend their license, including ZNS and cannabidiol (see www.…”