ES-481 / Avalo Therap, ES Therap - LARVOL DELTA

Non-surgical treatment of essential tremor: What's in store? (PubMed, Parkinsonism Relat Disord) - "While ACP-711 is a newly investigated positive allosteric modulator (PAM) of GABA-A receptors, other PAMs (SAGE-324 and PRAX-114) have been withdrawn after failure to demonstrate statistically significant effects in clinical trials. This has also extended to include highly selective Cav3 antagonists (T-type calcium channel blockers): suvecaltamide (JZP385) and NBI-827104/ACT-7099478. By contrast, ulixacaltamide (PRAX-944) has been recently found to be effective and safe in a large phase 3 trial. ES-481, a novel selective antagonist of transmembrane AMPA receptor regulatory protein (TARP)-γ8-dependent AMPA receptors, has been tested in a small trial in Canada, complicated by early participant drop-out...Although many compounds have failed during advanced clinical development, others remain in the pipeline. This renewed interest in the treatment of ET, along with a better understanding of its pathophysiology and clinical trial design, could ultimately lead to newer..."

Journal • Review • Essential Tremor • Movement Disorders • Orthopedics • CAV3

Progress report on new epilepsy treatments: A summary of the Eighteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVIII). II. Treatments in more advanced clinical development. (PubMed, Epilepsia) - "The treatments reviewed include bexicaserin, a selective 5-hydroxytryptamine (5-HT, serotonin) type 2C (5-HT2C) receptor superagonist investigated as a treatment for developmental and epileptic encephalopathies (DEEs); BMB-101, a selective 5-HT2C 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-HT2A and 5-HT2B 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..."

Journal • Absence Seizure Disorder • CNS Disorders • Developmental Disorders • Epilepsy • Gene Therapies • Psychiatry • GRIN2B • NAV1 • SCN8A

A first in disease trial of the safety, tolerability, and anti-seizure effects of ES-481 in drug-resistant epilepsy. (PubMed, Epilepsia Open) - P2, P2a | "This was a first-in-disease, proof-of-concept early-phase trial of a novel anti-seizure medication, ES-481, in adults with a broad group of patients drug-resistant epilepsy, who continue to have seizures despite treatment with currently available medications. ES-481 was generally safe and well tolerated, and participants receiving the highest dose showed fewer seizures compared with placebo. These findings suggest ES-481 may offer a promising new treatment approach for people with difficult-to-control epilepsy, supporting the need for larger future studies."

Journal • CNS Disorders • Epilepsy • Mood Disorders • Psychiatry

A Phase 1, Open-Label, Single Ascending Dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of ES-481 After Oral Administration in Healthy Volunteers. (PubMed, Eur J Drug Metab Pharmacokinet) - "ES-481 doses up to 100 mg were found to be safe and well tolerated. There were no safety findings in this study of concern, and all of the adverse events related to the administration of ES-481 were mild and transient This study describes the pharmacokinetic parameters of ES-481 for the proposed efficacious dose range of 75-100 mg/day of ES-481 for the treatment of DRE."

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

Efficacy and Safety of ES-481, a Novel TARP Inhibitor, in Drug-resistant Epilepsy: A Double-blind Randomized Placebo Controlled Phase IIa Trial (AAN 2024) - P2a | "ES-481 demonstrated evidence of anti-seizure efficacy compared to the placebo in patients with DRE. ES-481 dosing up to 75 mg bid was safe and well tolerated."

Clinical • P2a data • CNS Disorders • Epilepsy • Hematological Disorders

Efficacy, Safety and Pharmacokinetics of ES-481 in Adult Patients With Drug Resistant Epilepsy (clinicaltrials.gov) - P2a | N=24 | Recruiting | Sponsor: ES Therapeutics Australia Pty Ltd | Trial completion date: Oct 2022 ➔ Dec 2023 | Trial primary completion date: Mar 2022 ➔ Dec 2023

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

Efficacy, Safety, and Pharmacokinetics of ES-481 in Adult Patients With Essential Tremors (clinicaltrials.gov) - P2a | N=24 | Recruiting | Sponsor: ES Therapeutics Australia Pty Ltd | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Essential Tremor • Movement Disorders