vormatrigine (PRAX-628) / 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

POWER2: Randomized Clinical Trial Evaluating the Efficacy and Safety of Vormatrigine in Adults With Focal Seizures (clinicaltrials.gov) - P3 | N=300 | 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

PRAX-628-322: A Double-blind, Randomized Clinical Trial Evaluating the Efficacy and Safety of Vormatrigine in Adults with Focal Seizures (clinicaltrialsregister.eu) - P2/3 | N=60 | Recruiting | Sponsor: Praxis Precision Medicines Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Epilepsy

PRAX-628-322: A Double-blind, Randomized Clinical Trial Evaluating the Efficacy and Safety of Vormatrigine in Adults with Focal Seizures (clinicaltrialsregister.eu) - P2/3 | N=60 | Not yet recruiting | Sponsor: Praxis Precision Medicines Inc. | N=27 ➔ 60

Enrollment change • CNS Disorders • Epilepsy

PRAX-628-322: A Double-blind, Randomized Clinical Trial Evaluating the Efficacy and Safety of Vormatrigine in Adults with Focal Seizures (clinicaltrialsregister.eu) - P2/3 | N=60 | Not yet recruiting | Sponsor: Praxis Precision Medicines Inc.

New P2/3 trial • CNS Disorders • Epilepsy

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

Updates from the First-in-human Phase 1 Clinical Trial Evaluating the Safety, Tolerability, Pharmacokinetics and Food Effect of Vormatrigine in Healthy Participants (AAN 2026) - "Findings from the 45 mg cohort highlight the highest multiples of the predicted therapeutically effective concentration achieved to date, with expected translation to patient benefit. These results support flexible dosing regimens up to 45 mg in the ongoing vormatrigine ENERGY program."

Clinical • First-in-human • P1 data • PK/PD data

Vormatrigine Rapidly Reduces Seizures in Adults with Treatment-resistant Epilepsy: Results from the RADIANT Study (AAN 2026) - P2 | "Vormatrigine demonstrated consistent efficacy across background ASMs (including ~30% on cenobamate), baseline seizure burden and seizure subtypes.Most TEAEs were mild-to-moderate and transient. Conclusions These results build on vormatrigine data to date, positioning it as a fast-acting, precision once-daily ASM with minimal drug–drug interactions and a favorable safety profile. Completed RADIANT study findings are anticipated to further support advancement of the vormatrigine ENERGY program."

Clinical • CNS Disorders • Epilepsy

POWER1 – A Double-blind, Randomized, Multicenter Phase 2/3 Study Evaluating the Efficacy and Safety of Vormatrigine in Adults with Focal Onset Seizures (AAN 2026) - "Enrollment is ongoing with topline data anticipated by year end 2025. Conclusions Expanding on preclinical and preliminary clinical data, the POWER1 study examines the efficacy, safety and pharmacokinetics of vormatrigine as an ideal precision ASM for FOS."

Clinical • P2/3 data • CNS Disorders • Epilepsy

PRAX-628-322: A Double-blind, Randomized Clinical Trial Evaluating the Efficacy and Safety of Vormatrigine in Adults with Focal Seizures (clinicaltrialsregister.eu) - P2/3 | N=27 | Not yet recruiting | Sponsor: Praxis Precision Medicines Inc.

New P2/3 trial • CNS Disorders • Epilepsy

PRAX-628-322: A Double-blind, Randomized Clinical Trial Evaluating the Efficacy and Safety of Vormatrigine in Adults with Focal Seizures (clinicaltrialsregister.eu) - P2/3 | N=12 | Not yet recruiting | Sponsor: Praxis Precision Medicines Inc.

New P2/3 trial • CNS Disorders • Epilepsy

POWER2: Double-blind, Randomized Clinical Trial Evaluating the Efficacy and Safety of Vormatrigine in Adults With Focal Seizures (clinicaltrials.gov) - P3 | N=300 | Recruiting | Sponsor: Praxis Precision Medicines

New P3 trial • CNS Disorders • Epilepsy

PRAX-628-323: Open Label Extension Clinical Trial of Vormatrigine in Adult Patients with Epilepsy. (clinicaltrialsregister.eu) - P2/3 | N=56 | Recruiting | Sponsor: Praxis Precision Medicines Inc.

New P2/3 trial • CNS Disorders • Epilepsy

Clinical Trial of Vormatrigine in Adult Patients With Epilepsy (clinicaltrials.gov) - P3 | N=700 | Enrolling by invitation | Sponsor: Praxis Precision Medicines

New P3 trial • CNS Disorders • Epilepsy

Vormatrigine Exhibits a Favorable Drug-Drug Interaction Profile Supporting Broad Combination Use with Antiseizure Medications (AES 2025) - "Key enzymes assessed included CYP1A2, 2C19, 3A4, and UGT isoforms, along with major efflux and uptake transporters.Clinically, the Phase 1 PRAX-628-102 study enrolled healthy adults and examined the pharmacokinetics (PK) of single 10 mg doses of vormatrigine alone and in combination with fluvoxamine (CYP1A2/2C19 inhibitor), itraconazole (CYP3A4 inhibitor) and probenecid (non-selective UGT inhibitor). Vormatrigine exhibits a highly favorable DDI profile, supported by both preclinical mechanistic studies and human PK data. With no clinically meaningful interactions observed with inhibitors or inducers of major CYP and UGT pathways—except a moderate effect via CYP1A2—vormatrigine is well-suited for use in multi-drug epilepsy regimens, including a broad array of ASMs without the need for dose adjustments. These findings reinforce vormatrigine's potential as a best-in-class sodium channel modulator and support its continued clinical development in the ENERGY program for..."

CNS Disorders • Epilepsy • ABCB1 • CYP1A2

Vormatrigine Rapidly Reduces Seizures in Adults with Treatment-Resistant Epilepsy: Results from the RADIANT Study (AES 2025) - P2 | "Vormatrigine delivered rapid seizure control within 1 week, with sustained response over 8 weeks alongside unprecedented seizure reduction and freedom in the setting of modern background ASMs, including ~30% on cenobamate. Topline RADIANT study results build on preclinical and early clinical data, positioning vormatrigine as a fast-acting, precision once-daily ASM with minimal drug–drug interactions and a favorable safety profile. These results strongly support accelerated advancement of Phase 3 studies in the vormatrigine ENERGY program."

Clinical • Late-breaking abstract • CNS Disorders • Epilepsy

Praxis Precision Medicines Announces Positive, Best-in-Disease Topline Results in Patients with Focal Onset Seizures from the RADIANT Study of Vormatrigine (Praxis) - "Dosing with vormatrigine over 8 weeks led to 56.3% median reduction in seizure frequency; Approximately 22% of patients reached 100% reduction in seizure frequency in the last 28 days on treatment; Rapid and sustained response, with over 54% of patients achieving 50% response in the first week; Vormatrigine was generally well tolerated and continues to demonstrate favorable safety profile...'We are well on track to complete the pivotal, 12-week POWER1 study in Q4 and, based on the results from RADIANT, expect to initiate the POWER2 study shortly.'"

New trial • P2 data • Trial completion date • CNS Disorders

Updates from the First-in-human Phase 1 Clinical Trial Evaluating the Safety, Tolerability, Pharmacokinetics and Food Effect of Vormatrigine in Healthy Participants (P11-4.006). (PubMed, Neurology) - "Petrou has received intellectual property interests from a discovery or technology relating to health care. Marcio Souza has received personal compensation for serving as an employee of Praxis Precision Medicines."

Clinical • Journal • P1 data • PK/PD data

Vormatrigine (PRAX-628) for Focal Onset Seizures and Generalized Epilepsy (GlobeNewswire) - "Praxis has initiated the RADIANT Phase 2, open-label, single-arm study for FOS and generalized epilepsy assessing seizure burden with vormatrigine treatment, with topline results expected by mid-year 2025. Praxis has also initiated the POWER1 Phase 2/3 registrational study of vormatrigine for treatment resistant FOS, with topline results anticipated in the second half of 2025. POWER2, the second registrational study for FOS, is on track to begin enrollment in the second half of 2025."

New trial • P2 data • P2/3 data • CNS Disorders • Epilepsy

Updates from the First-in-human Phase 1 Clinical Trial Evaluating the Safety, Tolerability, Pharmacokinetics and Food Effect of Vormatrigine in Healthy Participants (AAN 2025) - "Vormatrigine demonstrated consistent safety, tolerability, and PK profiles, with no significant food effect. These results support flexible dosing regimens up to 45mg in the ongoing vormatrigine ENERGY program."

Clinical • P1 data • PK/PD data

Praxis Precision Medicines to Host PRAX-628 Program Update (GlobeNewswire) - "Praxis Precision Medicines...announced that it will host a virtual program update to discuss its PRAX-628 program in epilepsy on Tuesday, March 26, 2024 at 8:00 a.m. ET."

Clinical • 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

Praxis Precision Medicines Provides Corporate Update and Reports Fourth Quarter and Full Year 2022 Financial Results (GlobeNewswire) - "Topline results expected for each of three clinical-stage epilepsy programs in 2023 – PRAX-222 first-in-patient EMBRAVE Study safety data mid-2023, PRAX-628 first-in-human Phase 1 data mid-2023, PRAX-562 Phase 2 EMBOLD Study results in 2H23."

P1 data • P2 data • CNS Disorders • Epilepsy

Praxis Precision Medicines to Present at the American Epilepsy Society 2022 Annual Meeting (GlobeNewswire) - "Praxis Precision Medicines, Inc...announced that it will deliver presentations on its epilepsy programs at the American Epilepsy Society (AES) 2022 Annual Meeting, held December 2-6, 2022 in Nashville, Tennessee....'It’s an incredibly exciting time for Praxis and our epilepsy portfolio, with first-in-patient studies for PRAX-222 and PRAX-562 and a first-in-human study for PRAX-628 expected to start shortly'....Together with pharmacokinetic findings demonstrating a 13-fold increase in concentrations compared to preclinical maximal electroshock seizure effects, our results are consistent with earlier work suggesting a wide therapeutic window for PRAX-562."

New trial • P1 data • Preclinical • CNS Disorders • Epilepsy