Jacqueline French

The field of epilepsy has undergone substantial advances as we develop novel drugs and devices. Yet considerable challenges remain in developing broadly effective, well‐tolerated treatments, but also precision treatments for rare epilepsies and seizure‐monitoring devices. We summarize major recent and ongoing innovations in diagnostic and therapeutic products presented at the seventeenth Epilepsy Therapies & Diagnostics Development (ETDD) conference, which occurred May 31 to June 2, 2023, in Aventura, Florida. Therapeutics under development are targeting genetics, ion channels and other neurotransmitters, and many other potentially first‐in‐class interventions such as stem cells, glycogen metabolism, cholesterol, the gut microbiome, and novel modalities for delivering electrical neuromodulation.

Objective:Evaluate the trajectory of epilepsy in treatment resistant patients in the presence or absence of devices.Background:Several long-term open label trials of devices to treat epilepsy (vagus Nerve Stimulator (VNS), Responsive Neurostimulator (RNS), Deep Brain Stimulator (DBS) have demonstrated a reduction in seizures over time, suggesting “disease modification”, but it is unknown if seizure trajectories differ in patients with or without devices. We evaluated trajectories in patients in the Human Epilepsy Project 2 (HEP2) with and without devices.Design/Methods:HEP2 subjects met the following qualifications: experienced failure of adequate trials of 4 anti-seizure medicines (ASMs), having≥ 2 focal seizures per month for 3 months before enrollment, and receiving≥ 1 ASM at baseline. Seizure frequency was collected monthly. Progress and activity of neuromodulation devices were recorded at each …

Epilepsy diagnosis is often delayed or inaccurate, exposing people to ongoing seizures and their substantial consequences until effective treatment is initiated. Important factors contributing to this problem include delayed recognition of seizure symptoms by patients and eyewitnesses; cultural, geographical, and financial barriers to seeking health care; and missed or delayed diagnosis by health-care providers. Epilepsy diagnosis involves several steps. The first step is recognition of epileptic seizures; next is classification of epilepsy type and whether an epilepsy syndrome is present; finally, the underlying epilepsy-associated comorbidities and potential causes must be identified, which differ across the lifespan. Clinical history, elicited from patients and eyewitnesses, is a fundamental component of the diagnostic pathway. Recent technological advances, including smartphone videography and genetic testing, are …

The International League Against Epilepsy (ILAE) introduced a classification for seizure types in 2017 and updated the classification for epilepsy syndromes in 2022. These classifications aim to improve communication among healthcare professionals and help patients better describe their condition. So far, regulatory agencies have used different terminology. This paper stresses the crucial need for consistently adopting ILAE terminology in both regulatory processes and clinical practice. It highlights how language plays a significant role in healthcare communication and how standardized terminology can enhance patient comprehension. The ongoing review of guidelines by regulatory bodies offers a timely opportunity. Aligning regulatory terminologies holds the potential to facilitate discussions on future drug development and harmonize practices across diverse regions, ultimately fostering improved care and …

Objective:To report interim 18-month data from an ongoing, long-term, open-label extension (OLE) of a Phase 2b study (X-TOLE) of XEN1101 in adults with focal onset seizures (FOS).Background:In the double-blind period (DBP) of X-TOLE, XEN1101 (10, 20, and 25 mg QD with food) showed a dose-dependent, statistically significant, and rapid-onset reduction in seizure frequency. We report interim 18-month OLE safety and efficacy data.Design/Methods:Eligible patients enrolled in the 5-year OLE at 20 mg QD with food. Assessments occurred at week 3 in the OLE and at 3-month intervals thereafter. Safety assessments included treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Primary efficacy outcome was median percentage change (MPC) in monthly (28-day) FOS frequency from DBP baseline.Results:285 patients completed the DBP and 275 (96.5%) enrolled in the OLE. At the …

Objective:We aim to understand the value of a clinical adjudication committee in verifying the diagnosis of new onset focal epilepsy.Background:Human Epilepsy Project (HEP) 1 is a multicenter prospective observational study of newly treated focal epilepsy patients with a goal of identifying biomarkers predictive of patient prognosis. Significant effort was employed to ensure proper enrollment including an adjudication committee.Design/Methods:Subjects were submitted for enrollment if they were deemed to have a> 80% likelihood of focal epilepsy and were seen within four months of treatment initiation. If subjects had a normal or no MRI/EEG, or if eligibility was in question for any other reason, they were adjudicated by 4 expert epileptologists to establish a consensus agreement on the diagnosis. Details of history, MRI and EEG findings at time of enrollment for each group were analyzed, along with reasons for …

Objective This study was undertaken to conduct external validation of previously published epilepsy surgery prediction tools using a large independent multicenter dataset and to assess whether these tools can stratify patients for being operated on and for becoming free of disabling seizures (International League Against Epilepsy stage 1 and 2). Methods We analyzed a dataset of 1562 patients, not used for tool development. We applied two scales: Epilepsy Surgery Grading Scale (ESGS) and Seizure Freedom Score (SFS); and two versions of Epilepsy Surgery Nomogram (ESN): the original version and the modified version, which included electroencephalographic data. For the ESNs, we used calibration curves and concordance indexes. We stratified the patients into three tiers for assessing the chances of attaining freedom from disabling seizures after surgery: high (ESGS = 1, SFS = 3–4, ESNs > 70 …

Objective:To report the impact of baseline disease severity on the percentage of patients achieving a≥ 50% reduction in seizure frequency (RR50) in the double-blind period (DBP) of a phase 2b study (X-TOLE) of XEN1101 in adults with focal onset seizures (FOS).Background:In the DBP, XEN1101 showed a significant, dose-dependent, and rapid-onset reduction in FOS frequency in adults with a median of 13.5 seizures/month and 6 tried and stopped antiseizure medications (ASMs) at baseline. 50.5% were taking 3 concomitant ASMs. A post hoc analysis suggested that the efficacy of XEN1101, measured by the median percentage change (MPC) in monthly FOS frequency, may be most pronounced in patients with less-severe disease. We report the potential impact of baseline disease severity on the RR50, another widely used endpoint for evaluating ASMs.Design/Methods:Patients (n= 325) received 25, 20, or …