elsunersen (PRAX-222) / RogCon, Ionis, 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

A Clinical Trial of PRAX-222 in Pediatric Participants With Early Onset SCN2A Developmental and Epileptic Encephalopathy (clinicaltrials.gov) - P1/2 | N=60 | Active, not recruiting | Sponsor: Praxis Precision Medicines | Trial completion date: Sep 2027 ➔ Feb 2028 | Trial primary completion date: Aug 2025 ➔ Apr 2026 | Recruiting ➔ Active, not recruiting

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

A Clinical Trial of Elsunersen in Pediatric SCN2A-DEE to Assess Efficacy and Safety (clinicaltrials.gov) - P3 | N=40 | Recruiting | Sponsor: Praxis Precision Medicines | Trial primary completion date: Jun 2026 ➔ Dec 2026

Trial primary completion date • CNS Disorders • Epilepsy • Pediatrics

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 Receives FDA Breakthrough Therapy Designation for Elsunersen for the Treatment of Seizures Associated with SCN2A Developmental and Epileptic Encephalopathy Caused by Gain of Function Variants (The Manila Times) - "The Breakthrough Therapy Designation (BTD) was granted based on the positive results from the EMBRAVE Part A trial of elsunersen"

Breakthrough therapy • CNS Disorders

PRAX-222-311: A Clinical Trial to Investigate the Efficacy, Safety and Pharmacokinetics of Elsunersen in Children (clinicaltrialsregister.eu) - P2/3 | N=25 | Not yet recruiting | Sponsor: Praxis Precision Medicines Inc. | N=10 ➔ 25

Enrollment change • CNS Disorders • Epilepsy • Pediatrics

PRAX-222-311: A Clinical Trial to Investigate the Efficacy, Safety and Pharmacokinetics of Elsunersen in Children (clinicaltrialsregister.eu) - P2/3 | N=10 | Not yet recruiting | Sponsor: Praxis Precision Medicines Inc. | N=20 ➔ 10

Enrollment change • CNS Disorders • Epilepsy • Pediatrics

Clinical Updates from the Elsunersen Emergency Use Program: A Novel ASO for Treatment of Early Onset SCN2A Developmental and Epileptic Encephalopathy (AAN 2026) - "Conclusions Elsunersen’s clinical experience to date demonstrates a well-tolerated, consistent and meaningful therapeutic response. Ongoing follow up will determine long-term effect on seizures and associated comorbidities."

Clinical • CNS Disorders • Developmental Disorders • Dystonia • Epilepsy • Movement Disorders

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

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

From Symptomatic Therapies to Disease-Modifying Approaches for Neuronal Sodium Channel Disorders. (PubMed, Int J Mol Sci) - "Additionally, pharmacological agents such as fenfluramine, stiripentol, and cannabidiol, although not acting directly on sodium channels, represent recognized therapeutic options for SCN1A-related Dravet syndrome. This review summarizes recent advances in approved and investigational treatments for sodium channel-related neurological disorders, highlighting the transition from symptomatic to precision therapies."

Journal • Review • CNS Disorders • Epilepsy • Gene Therapies

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

Voltage-gated sodium channels in the nervous system: Molecular physiology to therapeutic interventions. (PubMed, Neural Regen Res) - "It analyzes two major categories of conventional sodium channel blockers and their applications: antiepileptic drugs (such as carbamazepine, lamotrigine, and phenytoin) and antiarrhythmic drugs (such as lidocaine, flecainide, and quinidine)...Additionally, this review evaluates gabapentin, cannabidiol, and calcium channel blockers with different mechanisms of action...This review also highlights advances in gene therapy for specific diseases, such as STK-001, which promotes effective splicing of the SCN1A gene, and ETX101, which utilizes adeno-associated virus 9 vectors to deliver engineered transcription factors...Furthermore, this review summarizes some innovative therapeutic agents in clinical trials, including PRAX-222 (for SCN2A gain-of-function mutation-related epilepsy), which has received Food and Drug Administration orphan drug designation, and the selective Nav1.6 inhibitor NBI-921352 (for SCN8A-related epilepsy). Collectively, this review comprehensively..."

Journal • Autism Spectrum Disorder • CNS Disorders • Epilepsy • Gene Therapies • Genetic Disorders • Migraine • Ophthalmology • Pain • NAV1 • SCN8A

A Clinical Trial of Elsunersen in Pediatric SCN2A-DEE to Assess Efficacy and Safety (clinicaltrials.gov) - P3 | N=50 | Recruiting | Sponsor: Praxis Precision Medicines | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Epilepsy • Pediatrics

Randomized, Double-blind Trial of Elsunersen in Pediatric SCN2A-DEE to Assess Efficacy and Safety (clinicaltrials.gov) - P3 | N=50 | Not yet recruiting | Sponsor: Praxis Precision Medicines

New P3 trial • CNS Disorders • Epilepsy • Pediatrics

Antisense oligonucleotide treatment in a preterm infant with early-onset SCN2A developmental and epileptic encephalopathy. (PubMed, Nat Med) - "These data provide preliminary insights on the safety and efficacy of elsunersen in a preterm infant. Additional investigation on the benefits of elsunersen in clinical trials is warranted."

Journal • CNS Disorders • Epilepsy

Elsunersen (PRAX-222) for early-seizure-onset SCN2A-DEE (GlobeNewswire) - "EMBRAVE3 will be a global, 24-week, double-blind, sham-procedure controlled study, with approximately 40 early-onset SCN2A-DEE patients, and is anticipated to start enrolling patients by mid-year 2025. The second cohort of the EMBRAVE study evaluating safety and efficacy of elsunersen versus sham procedure continues enrolling patients in Brazil, with topline readout anticipated in the first half of 2026."

New trial • P1/2 data • CNS Disorders • Epilepsy

Clinical Updates from the Elsunersen Emergency Use Program: A Novel ASO for Treatment of Early Onset SCN2A Developmental and Epileptic Encephalopathy (AES 2024) - "Seizure frequency remains stable with ongoing dosing; maintained after tapering phenytoin at age 14 months, with no worsening of neurodevelopment at age 18 months.In the Australian patient, 2 weeks after the second dose, a 0.5 ml weekly reduction of ethosuximide was achieved, with facial myoclonus subsiding during waking hours. Together with EMBRAVE Part 1 findings, clinical experience in ongoing emergency use programs in the US, Germany, and Australia demonstrate a well-tolerated, consistent and meaningful therapeutic response to elsunersen. Ongoing follow up will determine long-term effect on seizures and associated comorbidities."

Clinical • CNS Disorders • Developmental Disorders • Dystonia • Epilepsy • Movement Disorders • NAV1

A Clinical Trial of PRAX-222 in Pediatric Participants with Early Onset SCN2A Developmental and Epileptic Encephalopathy (clinicaltrials.gov) - P1/2 | N=60 | Recruiting | Sponsor: Praxis Precision Medicines | Active, not recruiting ➔ Recruiting | Trial completion date: Feb 2026 ➔ Sep 2027

Enrollment open • Trial completion date • CNS Disorders • Epilepsy • Pediatrics

A Clinical Trial of PRAX-222 in Pediatric Participants With Early Onset SCN2A Developmental and Epileptic Encephalopathy (clinicaltrials.gov) - P1/2 | N=60 | Active, not recruiting | Sponsor: Praxis Precision Medicines | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Epilepsy • Pediatrics

EMBRAVE: A Clinical Trial of PRAX-222, a Novel Antisense Oligonucleotide, in Pediatric Participants with Early Onset SCN2A Developmental and Epileptic Encephalopathy (AES 2023) - P1/2 | "PRAX-222 has potential to be the first disease-modifying treatment for early onset SCN2A GoF DEE. The EMBRAVE trial is intended to identify and confirm a safe and efficacious PRAX-222 dose for seizure control, with Part 1 designed to assess preliminary safety and inform subsequent dose escalation and trial continuation."

Clinical • CNS Disorders • Epilepsy • Pediatrics

A Novel Antisense Oligonucleotide for the Treatment of Early Onset SCN2A Developmental and Epileptic Encephalopathy: A First-in-Patient Report in a Preterm Infant with Refractory Status Epilepticus (AES 2023) - "First-in-patient findings highlight potential for PRAX-222 to be the first disease-modifying treatment for early onset GoF SCN2A-DEE, with early clinical experience in combination with SCBs indicating safety and a temporal association with seizure reduction including cessation of previous SE. Ongoing follow up will determine long-term effects of repeated PRAX-222 administration on seizure frequency and intensity, and associated comorbidities."

Clinical • Prematurity • CNS Disorders • Epilepsy • Gastrointestinal Disorder • Movement Disorders • Sleep Disorder

Praxis Precision Medicines Receives PRIME Designation from the EMA for elsunersen (PRAX-222) for Treatment of SCN2A Gain of Function Developmental Epilepsies (GlobeNewswire) - "Praxis Precision Medicines, Inc...today announced that the European Medical Agency (EMA) has awarded its Priority Medicines (PRIME) designation for elsunersen (PRAX-222) for the treatment of SCN2A Gain of Function (GoF) developmental and epileptic encephalopathy (DEE). The EMA’s PRIME designation...was granted based on the Part 1 data from the EMBRAVE study that showed a reduction in seizures and improvement in seizure free days, as well as preclinical data."

European regulatory • CNS Disorders • Epilepsy

Praxis Precision Medicines to Present at the American Academy of Neurology 2023 Annual Meeting (GlobeNewswire) - "Praxis Precision Medicines, Inc....announced that it will deliver presentations on its clinical stage programs at the upcoming American Academy of Neurology (AAN) 2023 Annual Meeting, held April 22-27, 2023 in Boston, Massachusetts....'Also, we expect to dose the first patients in our PRAX-222 EMBRAVE study and PRAX-562 EMBOLD study within the coming weeks and are excited to share data supporting these programs. Finally, we look forward to sharing new in-vivo results for PRAX-628 that highlight this program’s potential to be a best-in-class treatment for focal epilepsy patients'."

Clinical data • Preclinical • CNS Disorders • Epilepsy

A Clinical Trial of PRAX-222 in Pediatric Participants With Early Onset SCN2A Developmental and Epileptic Encephalopathy (clinicaltrials.gov) - P1/2 | N=60 | Recruiting | Sponsor: Praxis Precision Medicines

New P1/2 trial • CNS Disorders • Epilepsy • Pediatrics