E2730 / Eisai - LARVOL DELTA

In vivo biomarkers of GABAergic function in epileptic rats treated with the GAT-1 inhibitor E2730. (PubMed, Epilepsia) - "This study identified clinically relevant changes in multimodality imaging and functional purported biomarkers of GABAergic activity during E2730 treatment in epileptic and healthy control animals. These biomarkers could be utilized in clinical trials of E2730 and potentially other GABAergic drugs to provide surrogate endpoints, thereby reducing the cost of such trials."

Journal • Preclinical • CNS Disorders • Epilepsy • Solid Tumor

Pharmacological evaluation of E2730, a novel selective uncompetitive GAT1 inhibitor, on epileptiform activities in resected brain tissues from human focal cortical dysplasia ex vivo. (PubMed, Epilepsy Res) - "We used the same ex vivo assay system to assess carbamazepine (CBZ), an ASM often prescribed for focal epilepsy, as a reference. At the lower dose (100 µM), CBZ reduced the area of brain tissue showing epileptiform activity, whereas E2730 significantly decreased the number of epileptiforms. These findings suggest that E2730-both as a single agent and in combination with CBZ-merits evaluation in clinical trials involving patients with FCD."

Journal • Preclinical • CNS Disorders • Epilepsy

Delayed-onset nodules following Vycross hyaluronic acid filler treatment: reported rates from global post-marketing surveillance (EADV 2023) - "2020;8(4):e2730. The global reported rate of delayed-onset nodules associated with Vycross dermal fillers is low (<0.02%). Event rates have been noted to increase with early adoption of products, then decrease as utilization increases. 1Philipp-Dormston WG, Goodman GJ, De Boulle K, et al."

Clinical • P4 data • Aesthetic Medicine • Dermatology

E2730, an uncompetitive GABA transporter-1 inhibitor, suppresses epileptic seizures in a rat model of chronic mesial temporal lobe epilepsy. (PubMed, Epilepsia) - "This study shows that continuous subcutaneous infusion of E2730 over 7 days results in a marked, dose-dependent suppression of spontaneous recurrent seizures, with minimal adverse neurological effects, in a rat model of chronic MTLE. E2730 shows strong promise as an effective new ASM to be translated into clinical trials."

Journal • Preclinical • Anesthesia • CNS Disorders • Epilepsy

Discovery of E2730, a novel selective uncompetitive GAT1 inhibitor, as a candidate for anti-seizure medication. (PubMed, Epilepsia Open) - "E2730 is a novel, selective, uncompetitive GAT1 inhibitor, which acts selectively under the condition of increasing synaptic activity, contributing to a wide margin between therapeutic effect and motor incoordination."

Journal • CNS Disorders • Epilepsy • Fragile X Syndrome • Genetic Disorders

Hippocampal RNA sequencing in mice selectively bred for high and low activity. (PubMed, Genes Brain Behav) - "High and Low Activity strains of mice were bidirectionally selected for differences in open-field activity (DeFries et al., 1978, Behavior Genetics, 8: 3-13) and subsequently inbred to use as a genetic model for studying anxiety-like behaviors (Booher et al., 2021, Genes, Brain and Behavior, 20: e12730)...In addition, comparison of our top candidate genes with two previously curated High and Low Activity gene lists highlight 24 overlapping genes, where Ndufa13, which encodes the supernumerary subunit A13 of complex I, was the only gene to be included in all three lists. Mitochondrial dysfunction has recently been implicated as both a cause and effect of anxiety-related disorders and thus should be further explored as a possible novel pharmaceutical treatment for anxiety disorders."

Journal • Preclinical • CNS Disorders • Metabolic Disorders • Mood Disorders • Psychiatry

Multimodality Biomarkers of Effects of E2730, a GABA transporter-1 Inhibitor, in a Rat Model of Chronic Drug Resistant Mesial Temporal Lobe Epilepsy (AES 2022) - "Continuous infusion of E2730 by osmotic pump resulted in a marked, suppression of epileptic seizures in post-KASE rats, indicating strong promise that this will be an effective ASM for patients with chronic MTLE. Clinically translatable multimodality imaging and functional biomarkers of GABAergic activity show relevant changes with E2730 treatment that could represent predictive biomarkers for E2730 treatment responses."

Preclinical • CNS Disorders • Epilepsy • Immunology • Solid Tumor

Pharmacological E2730 Evaluation to Assess Epileptiform Activities in Human Epileptic Foci Ex-vivo (AES 2022) - "Antiepileptic effects were finally compared with those of Carbamazepine (CBZ) as a control. Investigations were conducted in seven focal epilepsy cases. These results indicate that E2730 has novel antiepileptic effects for managing human epileptic foci than conventional ASMs."

Preclinical • CNS Disorders • Epilepsy • Immunology • Inflammation • Oncology

A Study to Evaluate the Pharmacodynamic Activity of E2730 in Adult Participants With Photosensitive Epilepsy (clinicaltrials.gov) - P2 | N=6 | Terminated | Sponsor: Eisai Inc. | N=25 ➔ 6

Enrollment change • CNS Disorders • Epilepsy

Discovery of E2730, a Novel Selective Uncompetitive GAT-1 Inhibitor: In Vivo Characteristics (AES 2021) - "E2730 had broad efficacy in a variety of animal models of epilepsy with wide margin against effect on motor coordination. The unique characteristics of uncompetitive mode of GAT-1 inhibition by E2730 was demonstrated in microdialysis assay. E2730 increased extracellular GABA concentration in mouse hippocampus selectively in activated condition induced by high potassium, whereas noncompetitive GAT-1 inhibitor tiagabine increased GABA concentration both in physiological basal and activated conditions."

Preclinical • CNS Disorders • Epilepsy • Fragile X Syndrome • Genetic Disorders

E2730, a GABA Transporter-1 Inhibitor, Suppresses Epileptic Seizures in a Rat Model of Chronic Drug Resistant Mesial Temporal Lobe Epilepsy (AES 2021) - "This study shows that continuous infusion of E2730 by osmotic pumps over 7 days results in a marked, dose dependant suppression of spontaneous recurrent seizures, without any remarkable neurological adverse effects, in a rat model of chronic drug resistant mesial temporal lobe epilepsy. E2730 shows strong promise as an effective new treatment to be translated into clinical trials."

Preclinical • Anesthesia • Ataxia • CNS Disorders • Epilepsy • Immunology • Movement Disorders

Discovery of E2730, a Novel Selective Uncompetitive GAT-1 Inhibitor: In Vitro Characteristics (AES 2021) - "Among four distinct GAT subtypes, E2730 selectively inhibits hGAT1, which is predominantly expressed on presynaptic neurons. The inhibitory activity of E2730 against hGAT1-mediated GABA uptake is more potent with increasing GABA concentration. This is the characteristic of an uncompetitive inhibition mode."

Preclinical • CNS Disorders • Epilepsy

Eisai To Present Real-World Evidence And Convulsive Seizure Freedom Data Evaluating FYCOMPA (perampanel) Across Patient Types At 75th American Epilepsy Society (AES) Annual Meeting (PRNewswire) - "Eisai Inc. announced today that new data on its antiepileptic drug FYCOMPA® (perampanel) CIII will be presented at the 75th American Epilepsy Society (AES) Annual Meeting to be held from December 3 to December 7, 2021 in Chicago, Il. Eisai will present 42 posters including key early add-on FYCOMPA data as well as data in pediatric and elderly patients. Three posters will present data on E2730, a selective uncompetitive GAT-1 Inhibitor, underscoring the company's commitment to advance epilepsy research as part of its mission to help treat patients living with epilepsy."

P2 data • P3 data • P4 data • Retrospective data • CNS Disorders • Epilepsy

A Study to Assess the Safety and Tolerability of E2730 After Multiple Dose and the Food Effect After Single Dose in Healthy Participants (clinicaltrials.gov) - P1; N=32; Completed; Sponsor: Eisai Inc.; Recruiting ➔ Completed

Clinical • Trial completion

A Study to Assess the Safety and Tolerability of E2730 After Multiple Dose and the Food Effect After Single Dose in Healthy Participants (clinicaltrials.gov) - P1; N=40; Recruiting; Sponsor: Eisai Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

A Study to Assess the Safety and Tolerability of E2730 After Multiple Dose and the Food Effect After Single Dose in Healthy Participants (clinicaltrials.gov) - P1; N=40; Not yet recruiting; Sponsor: Eisai Inc.

Clinical • New P1 trial

A Study to Assess the Safety, Tolerability, and Pharmacokinetics of E2730 in Healthy Participants (clinicaltrials.gov) - P1; N=32; Recruiting; Sponsor: Eisai Inc.; Trial completion date: Jun 2018 ➔ Oct 2018; Trial primary completion date: Jun 2018 ➔ Oct 2018

Trial completion date • Trial primary completion date • Biosimilar

DIFFERING REFLECTIONS OF HODGKIN LYMPHOMA ON LOCAL AND DISTANT IMMUNOLOGICAL MICROENVIRONMENTS (ASPHO 2019) - "...We recently showed that the proportion of CD38/HLA-DR co-positive lymphocytes in affected lymph node (LN) tissue was an independent predictor of event-free survival (Pediatr Blood Cancer; 2018 Nov 15;65(11):e27307)... Our results indicate differences in lymphocyte make-up between affected LN tissue and BM, likely due to tumor cell activity, either through secretion of certain cytokines/chemokines and/or direct cell-to-cell interactions. Lack of difference between BM and PB cells may suggest presence of the same lymphoid tissue alterations affecting many sites outside the disease locations. Studies investigating the mechanisms and role of lymphocyte profile differences in LN and BM tissues are warranted."

IO Biomarker

A Study to Assess the Safety, Tolerability, and Pharmacokinetics of E2730 in Healthy Participants (clinicaltrials.gov) - P1; N=32; Completed; Sponsor: Eisai Inc.; Recruiting ➔ Completed

Clinical • Trial completion

A Study to Evaluate the Pharmacodynamic Activity of E2730 in Adult Participants With Photosensitive Epilepsy (clinicaltrials.gov) - P2; N=9; Terminated; Sponsor: Eisai Inc.; Recruiting ➔ Terminated; The study was stopped due to efficacy reasons.

Clinical • Trial termination