relutrigine (PRAX-562) / Praxis Precision Medicines - LARVOL DELTA

Antiseizure Medications in Development: Novel Mechanisms, Precision Therapy, and the Move Towards Disease Modification. (PubMed, Curr Issues Mol Biol) - "Functional-state-selective sodium channel modulation has emerged as a leading conceptual advance supported by converging mechanistic and early clinical evidence, exemplified by relutrigine (PRAX-562), a preferential persistent-current inhibitor for which a regulatory decision is pending in SCN2A/SCN8A-DEEs, and vormatrigine (PRAX-628), whose large open-label effect was not reproduced in a controlled (blinded) trial...Parallel advances include the selective Kv7 opener azetukalner; the dual-mechanism benchmark cenobamate; cholesterol-24-hydroxylase inhibition (soticlestat); selective serotonergic agonism (bexicaserin); glutamatergic precision agents (radiprodil); subtype-selective GABAA modulators (darigabat, ganaxolone); and gene-directed therapies (zorevunersen, elsunersen)... The pipeline reflects an ongoing shift from broad symptomatic agents toward mechanism-led, genotype-matched, and potentially disease-modifying treatments. This shift is tempered by a persistent..."

Journal • Review • CNS Disorders • Epilepsy • SCN8A

EMERALD: A Clinical Trial for Participants With DEE to Assess Efficacy, Safety, Tolerability, and PK of Relutrigine (clinicaltrials.gov) - P3 | N=160 | Active, not recruiting | Sponsor: Praxis Precision Medicines | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Epilepsy

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

Praxis Precision Medicines…announced that the…FDA notified Praxis that it has extended by three months the review period for its New Drug Application (NDA) for relutrigine for the treatment of SCN2A and SCN8A developmental and epileptic encephalopathies (DEEs), setting an updated PDUFA target action date from September 27, 2026 to December 27, 2026 (GlobeNewswire) - "The extension follows Praxis's submission of additional sensitivity analyses of existing clinical data, which the FDA has deemed a 'major amendment,' allowing additional time for the FDA to review. No new clinical studies were requested, and the FDA did not cite any safety or manufacturing concerns."

PDUFA • CNS Disorders • Developmental Disorders

EMERALD: A Clinical Trial for Participants With DEE to Assess Efficacy, Safety, Tolerability, and PK of Relutrigine (clinicaltrials.gov) - P3 | N=160 | Recruiting | Sponsor: Praxis Precision Medicines | Trial completion date: Jul 2027 ➔ Nov 2027 | Trial primary completion date: Jul 2026 ➔ Dec 2026

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

Recent Highlights and Anticipated Milestones (GlobeNewswire) - "The FDA has accepted Praxis’ NDA for ulixacaltamide for the treatment of ET and has set a target action date under the Prescription Drug User Fee Act (PDUFA) of January 29, 2027...The FDA has accepted with priority review the relutrigine NDA for the treatment of SCN2A and SCN8A DEEs, with a PDUFA target action date of September 27, 2026...Assuming successful initial NDA approval of relutrigine, the EMERALD study, if positive, would serve as the basis for a supplemental NDA submission in 2027."

PDUFA • CNS Disorders • Epilepsy • Essential Tremor

Evaluating the Therapeutic Potential of Emerging Precision Sodium Channel Modulators in Pain (AAN 2026) - "Oxaliplatin-Induced Peripheral Neuropathy (OIPN) – Reversal of cold allodynia was assessed in C57BL/6J mice using the acetone test (relutrigine) or in Sprague-Dawley rats using a cold immersion test (vormatrigine) following oxaliplatin pretreatment. In healthy volunteers, PRAX-1451 significantly reduced axonal excitability across NETT parameters, confirming NaV target engagement, while nociceptive thresholds remained unchanged. Conclusions Preclinical and human data demonstrate selective NaV modulation by relutrigine, vormatrigine, and PRAX-1451, supporting their potential as well-tolerated analgesics targeting peripheral NaV dysfunction, and advancing a translational platform for next-generation pain therapeutics."

CNS Disorders • Epilepsy • Musculoskeletal Pain • Neuralgia • Pain • Peripheral Neuropathic Pain

Efficacy and Safety of Relutrigine in Pediatric Participants with SCN2A- and SCN8A-related Developmental and Epileptic Encephalopathies: Pivotal EMBOLD Cohort 2 Study (AAN 2026) - P2/3 | "Conclusions Cohort 2 represents the pivotal, registration-enabling phase of the EMBOLD study in patients with SCN2A- and SCN8A-DEE. Efficacy and safety data are expected to further define relutrigine’s therapeutic potential and support its advancement as a precision sodium channel modulator for broad DEEs."

Clinical • CNS Disorders • Epilepsy • Pediatrics • SCN8A

EMERALD: A Phase 3, Randomized, Multi-center, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Relutrigine in Participants with Developmental and Epileptic Encephalopathies (AAN 2026) - "Conclusions Recent findings from the EMBOLD study demonstrated well-tolerated, pronounced seizure reduction and unprecedented seizure-free status in patients with SCN2A-DEE and SCN8A-DEE, with emerging preclinical data highlighting robust, differentiated efficacy in multiple DEE models. Findings from the EMERALD study are anticipated to provide further evidence for relutrigine’s potential to be a first- and best-in-class small molecule for DEEs."

Clinical • P3 data • PK/PD data • CNS Disorders • Developmental Disorders • Epilepsy • SCN8A

Complementary Antisense Oligonucleotide Treatment and Precision Sodium Channel Modulation for Early Onset SCN2A Developmental and Epileptic Encephalopathy: Emergency Use Case in a Preterm Infant with Refractory Status Epilepticus (AAN 2026) - "Relutrigine, a sodium channel functional state modulator, has demonstrated robust, sustained seizure reduction in a diverse DEE population...Seizure frequency remained stable, maintained after tapering phenytoin at 14 months, with no further neurodevelopmental worsening...Continued improvement in clinical status permitted a previously unattainable reduction in carbamazepine dosage. Conclusions First-in-patient findings point to elsunersen’s potential for enhancement via adjunctive precision sodium channel modulation addressing residual network hyperexcitability."

Clinical • Prematurity • CNS Disorders • Developmental Disorders • Epilepsy

Praxis Precision Medicines Announces FDA Acceptance and Priority Review of New Drug Application for Relutrigine in Patients with SCN2A and SCN8A DEEs (GlobeNewswire) - "The FDA has set a target action date under the Prescription Drug User Fee Act (PDUFA) of September 27, 2026...The NDA is supported by positive results from the EMBOLD study, which was stopped early for efficacy following a successful interim analysis and recommendation from the Data Monitoring Committee...Relutrigine is also being investigated in broad DEEs through the EMERALD trial, which is expected to be completed by the end of 2026."

FDA filing • PDUFA • Priority review • Trial completion date • CNS Disorders • Genetic Disorders

Praxis Precision Medicines…announced that the U.S. Food and Drug Administration (FDA) has accepted for priority review its New Drug Application (NDA) for relutrigine, for the treatment of SCN2A and SCN8A developmental and epileptic encephalopathies (DEEs) (GlobeNewswire) - "The FDA has set a target action date under the Prescription Drug User Fee Act (PDUFA) of September 27, 2026....The NDA is supported by positive results from the EMBOLD study, which was stopped early for efficacy following a successful interim analysis and recommendation from the Data Monitoring Committee....Relutrigine is also being investigated in broad DEEs through the EMERALD trial, which is expected to be completed by the end of 2026"

FDA filing • PDUFA • Priority review • Trial completion date • CNS Disorders • Developmental Disorders

Recent Highlights and Anticipated Milestones: Relutrigine for DEEs (GlobeNewswire) - "Praxis has submitted an NDA for relutrigine for the treatment of SCN2A and SCN8A DEEs based on the strong efficacy observed in the EMBOLD registrational cohort....Enrollment in the EMERALD study in broad DEEs is progressing well and is expected to be fully enrolled in the second half of 2026. Assuming successful initial NDA approval of relutrigine, the EMERALD study, if positive, would serve as the basis for a supplemental NDA submission in 2027."

FDA filing • Trial status • Epilepsy

EMBOLD: A Clinical Trial of PRAX-562 in Subjects With Developmental and Epileptic Encephalopathies (DEE) (clinicaltrials.gov) - P2/3 | N=77 | Active, not recruiting | Sponsor: Praxis Precision Medicines | Recruiting ➔ Active, not recruiting | Trial primary completion date: Mar 2026 ➔ Nov 2025

Enrollment closed • Trial primary completion date • CNS Disorders • Epilepsy • Pediatrics • SCN8A

What’s Ahead in 2026 and Beyond (GlobeNewswire) - "NDA submission to the FDA is expected by mid-February 2026...NDA submission to the FDA is expected by mid-February 2026 for SCN2A- and SCN8A-DEE...The EMERALD study enrolling broad DEEs is expected to complete in the second half of 2026. Assuming successful NDA approval of relutrigine, the EMERALD study, if positive, would serve as the basis for an sNDA submission by 2027....Clinical data from the EMBRAVE3 study, if successful, would serve as the basis for an NDA submission in 2027."

FDA filing • Trial status • Epilepsy • Essential Tremor

Praxis Precision Medicines Announces Plans to File an NDA for Relutrigine in SCN2A and SCN8A Developmental and Epileptic Encephalopathies in Early 2026 (GlobeNewswire)

FDA filing • Epilepsy

Preclinical Findings of Relutrigine, a Functional State Sodium Channel Modulator, Point to Anticonvulsant Potential in Dravet Syndrome with Greater Potency than Fenfluramine (AES 2025) - "Preliminary findings in a zebrafish model support relutrigine's anticonvulsant action in Dravet syndrome and the potential for superior efficacy over current standard-of-care. In combination with recent results from the EMBOLD study in SCN2A and SCN8A, these findings emphasize its promising potential to address significant unmet needs across broad DEEs."

Preclinical • CNS Disorders • Developmental Disorders • Epilepsy • SCN8A

Complementary Antisense Oligonucleotide Treatment and Precision Sodium Channel Modulation for Early Onset SCN2A DEE: Emergency Use Cases in a Preterm Infant with Refractory Status Epilepticus (AES 2025) - "Seizure frequency remained stable with ongoing dosing; maintained after tapering phenytoin at 14 months, with no neurodevelopmental worsening. Preliminary first-in-human findings highlight the potential for complementary use of elsunersen and relutrigine for early onset SCN2A DEE, which we hypothesize is due to targeting both the root genetic cause and downstream network hyperexcitability characteristic of this disease."

Clinical • Prematurity • CNS Disorders • Developmental Disorders • Epilepsy

Relutrigine Demonstrates Sustained Seizure Reduction with Continued Exposure on Top of Standard of Care: Results from the EMBOLD Open Label Extension (AES 2025) - P2/3 | "Relutrigine is poised to be a first-line, best-in-class treatment for broad DEEs, demonstrating well-tolerated, robust, short- and sustained long-term improvement in motor seizures alongside marked seizure freedom. A registration-enabling EMBOLD cohort extension is ongoing with topline results anticipated no later than 1H 2026. The EMERALD study is set to initiate globally by mid-2025 in a broader, pan-DEE patient population."

Clinical • CNS Disorders • Epilepsy • SCN8A

Praxis announces accelerated development path for relutrigine in SCN2A and SCN8A DEE patients following positive FDA feedback (GlobeNewswire) - "The FDA agreed that Praxis’ proposed interim analysis, if positive, may serve as the basis of the NDA submission in early 2026. The interim analysis is planned to be conducted in the fourth quarter of 2025....Enrollment for the EMERALD study began in the third quarter of 2025 and is expected to be complete in the second half of 2026, receiving strong interest in the geographies where it is planned. Assuming successful conclusion of the EMBOLD study and subsequent NDA approval, if positive, the EMERALD study would serve as the basis for an sNDA by 2027."

Enrollment status • FDA event • FDA filing • Epilepsy

EMERALD: A Clinical Trial for Participants With DEE to Assess Efficacy, Safety, Tolerability, and PK of Relutrigine (clinicaltrials.gov) - P3 | N=160 | Recruiting | Sponsor: Praxis Precision Medicines | Trial completion date: Feb 2027 ➔ Jul 2027 | Trial primary completion date: Apr 2026 ➔ Jul 2026

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

Praxis Precision Medicines Receives FDA Breakthrough Therapy Designation for Relutrigine for the Treatment of Seizures Associated with SCN2A and SCN8A Developmental and Epileptic Encephalopathies (GlobeNewswire) - "Praxis Precision Medicines, Inc...announced that the U.S. Food and Drug Administration (FDA) has granted BTD for relutrigine, a sodium channel functional state modulator for pediatric use for the treatment of patients with SCN2A and SCN8A DEEs...'The EMBOLD cohort 1 study supporting our application enrolled the most severe DEE population ever studied and included patients that failed three treatments on average before joining the study'...The EMBOLD registrational cohort 2 is currently ongoing and continues to enroll, with topline results expected no later than the first half of 2026, followed by a potential NDA filing."

Breakthrough therapy • P2 data • Epilepsy

EMERALD: A Clinical Trial for Participants With DEE to Assess Efficacy, Safety, Tolerability, and PK of Relutrigine (clinicaltrials.gov) - P3 | N=160 | Recruiting | Sponsor: Praxis Precision Medicines | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Epilepsy

EMERALD: Randomized, Double-Blind Study in Participants With DEE to Assess Efficacy, Safety, Tolerability, and PK of Relutrigine (clinicaltrials.gov) - P3 | N=160 | Not yet recruiting | Sponsor: Praxis Precision Medicines

New P3 trial • CNS Disorders • Epilepsy

Relutrigine (PRAX-562) for Developmental and Epileptic Epilepsies (DEEs) (GlobeNewswire) - "EMBOLD is currently enrolling patients with SCN2A and SCN8A DEEs in the registrational cohort 2, with topline results anticipated in the first half of 2026, followed by a potential NDA filing in 2026...Following recent regulatory interactions, Praxis anticipates initiating the EMERALD study for DEEs by mid-year 2025."

Clinical data • FDA filing • New trial • P2/3 data • CNS Disorders • Epilepsy