SCN8A-related epilepsy with encephalopathy

BOSTON, Sept. 04, 2024 (GLOBE NEWSWIRE) -- Praxis Precision Medicines, Inc. (NASDAQ: PRAX), a clinical-stage biopharmaceutical company translating genetic insights into the development of therapies for central nervous system (CNS) disorders characterized by neuronal excitation-inhibition imbalance, today announced that that it will present preclinical and clinical data from three of its epilepsy programs at the International League Against Epilepsy (ILAE) 15th European Epilepsy Congress (EEC), being held from September 7 to 11, 2024 in Rome, Italy. “We are pleased to highlight the continued progress across our portfolio of epilepsy assets, building on the strong evidence we have already generated in the elsunersen EMBRAVE study and the relutrigine EMBOLD study,” said Steven Petrou, chief scientific officer and co-founder of Praxis. “We are currently enrolling registrational trials for elsunersen and relutrigine, and look forward to initiating our ENERGY program with PRAX-628 this year.” Praxis at EEC 2024 | Roma Convention Center La Nuvola Connect with members of our team at booth #441 or head to one of our presentations listed below where we will share updates across our epilepsy portfolio. Oral Presentation Tuesday, September 10, 01:02 p.m. – 01:10 p.m. CESTLocation: CaravaggioSession: Platform Session – Pediatric Epileptology Significant Seizure Reduction in Pediatric Participants with Early Onset SCN2A Developmental and Epileptic Encephalopathy following Treatment with Elsunersen, a Novel Antisense Oligonucleotide: Findings from the EMBRAVE Study Poster Presentations Sunday – Tuesday, September 8 – 10, 1:30 p.m. – 3:00 p.m. CESTLocation: Forum P083. Pharmacokinetics, Tolerability and Cardiac Safety for PRAX-628, a Precision Medicine Therapeutic Set to Initiate Registration Enabling Studies for Focal Onset Seizures P898. 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 P908. EMBOLD: A Clinical Trial of PRAX-562 in Subjects with Developmental and Epileptic Encephalopathies P074. A Novel Translational Concordance Framework Identifies Preclinical Seizure Models with Highest Predictive Validity in Focal Onset Seizures P339. A Novel Method to Define an EEG Composite for the Detection of Drug Effects of Next Generation Small Molecules for Epilepsy About Relutrigine (PRAX-562)Relutrigine is a first-in-class small molecule in development for the treatment of developmental and epileptic encephalopathies (DEEs) as a preferential inhibitor of persistent sodium current, shown to be a key driver of seizure symptoms in severe DEEs. Relutrigine’s mechanism of precision sodium channel (NaV) modulation is consistent with superior selectivity for disease-state NaV channel hyperexcitability. In vivo studies of relutrigine have demonstrated dose-dependent inhibition of seizures up to complete control of seizure activity in SCN2A, SCN8A and other DEE mouse models. Relutrigine has been generally well-tolerated in three Phase 1 studies and has demonstrated biomarker changes indicative of NaV channel modulation. Data from the Phase 2 EMBOLD study demonstrated in a heavily pre-treated population a well-tolerated, robust, short- and long-term improvement in motor seizures alongside maintained seizure freedom in some patients with SCN2A- and SCN8A-DEE. Relutrigine has received Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation from the FDA, and ODD from the European Medicines Agency for the treatment of SCN2A-DEE and SCN8A-DEE. About PRAX-628PRAX-628 is a next-generation, functionally selective small molecule targeting the hyperexcitable state of NaV channels in the brain that is currently being developed as a once daily, oral treatment for adult focal onset seizures and generalized epilepsy. Preclinical data demonstrates PRAX-628 is differentiated from standard of care, with the potential to be best-in-class for focal onset seizures. In vitro, PRAX-628 has demonstrated superior selectivity for disease-state NaV channel hyperexcitability. In vivo studies of PRAX-628 have demonstrated unprecedented potency in the maximal electroshock seizure (MES) model, a highly predictive translational model for efficacy in focal epilepsy. Data from the PRAX-628-101 study demonstrated that PRAX-628 can be safely dosed in healthy subjects to greater than 15 times the predicted human equivalent of the rodent MES EC50, a translational indicator that suggests a therapeutic window with unprecedented magnitude relative to approved therapies. About Elsunersen (PRAX-222)Elsunersen is an antisense oligonucleotide (ASO) designed to selectively decrease SCN2A gene expression, directly targeting the underlying cause of early- onset SCN2A-DEE to treat seizures and other symptoms in patients with gain-of-function SCN2A mutations. In vitro studies of elsunersen have demonstrated reduction in both SCN2A gene expression and protein levels. In vivo, elsunersen has demonstrated significant, dose-dependent reduction in seizures, improvement in behavioral and locomotor activity and increased survival in SCN2A mouse models. Data from the EMBRAVE study demonstrated well-tolerated, significant and sustained seizure reduction in patients with SCN2A-DEE. Elsunersen has received Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation (RPD) from the FDA, and ODD and PRIME designations from the European Medicines Agency (EMA) for the treatment of SCN2A-DEE. The Elsunersen program is ongoing under a collaboration with Ionis Pharmaceuticals, Inc. (NASDAQ: IONS), and RogCon, Inc. To learn more about the EMBRAVE study, please visit https://www.embravestudy.com/. About Praxis  Praxis Precision Medicines is a clinical-stage biopharmaceutical company translating insights from genetic epilepsies into the development of therapies for CNS disorders characterized by neuronal excitation-inhibition imbalance. Praxis is applying genetic insights to the discovery and development of therapies for rare and more prevalent neurological disorders through our proprietary small molecule platform, Cerebrum™, and antisense oligonucleotide (ASO) platform, Solidus™, using our understanding of shared biological targets and circuits in the brain. Praxis has established a diversified, multimodal CNS portfolio including multiple programs across movement disorders and epilepsy, with four clinical-stage product candidates. For more information, please visit www.praxismedicines.com and follow us on Facebook, Instagram, LinkedIn and Twitter/X.

Five patients receiving relutrigine went for 28 days without a seizure, compared to none in the placebo cohort, Praxis Precision Medicines noted. Praxis Precision Medicines has scored another midphase win in epilepsy this year, with its sodium channel inhibitor shown to reduce seizures in children with two specific types of the neurological disorder.The EMBOLD study enrolled 16 individuals aged between 2 and 18 years who had been diagnosed with early-onset SCN2A-DEE or SCN8A-DEE—forms of epilepsy for which there are no approved treatments. These patients either received placebo or relutrigine, which inhibits persistent sodium current, a key driver of seizure symptoms in SCN2A-DEE and SCN8A-DEE.Participants who received relutrigine saw an average 46% reduction in their seizures during the double-blind part of the study, Praxis said in a Sept. 3 release. Disrupted movement improved by 23% based on a clinician’s assessment at Week 16, while communication improved by 31% and seizure severity and intensity by 62%.Five patients receiving relutrigine went for 28 days without a seizure, compared to none in the placebo cohort, the biotech noted. The primary endpoint of the trial was the drug’s safety, and Praxis reported that no patients discontinued their treatment due to an adverse event. Relutrigine was “generally safe and well tolerated,” the company said, with seven patients increasing their daily dose from 0.5 mg/kg to 1 mg/kg during the trial.The most common adverse events were infections, vomiting, pyrexia, somnolence and constipation, the biotech said.“When comparing to the baseline rates, patients in EMBOLD had over 2,000 fewer seizures since the beginning of the study,” Praxis CEO Marcio Souza said in the release.“Seizure freedom is the ultimate goal for patients, and we were humbled by the progress made with relutrigine during the EMBOLD study with over 30% of patients achieving this life-altering milestone,” Souza added.Praxis scored another midphase epilepsy win back in March when a high dose of its next-generation NaV blocker PRAX-628 was linked to a 100% complete response rate in epilepsy patients with photoparoxysmal response, a form of photosensitivity.

Placebo-adjusted monthly motor seizure reduction of 46% during double-blind period Over 30% of patients achieved seizure freedom status while on relutrigine Meaningful gains observed in alertness, communication and seizure severity 75% reduction in median seizure rate seen for patients in the long-term extension Registrational phase of the EMBOLD study for SCN2A and 8A initiated BOSTON, Mass., Sept. 03, 2024 (GLOBE NEWSWIRE) -- Praxis Precision Medicines, Inc. (NASDAQ: PRAX), a clinical-stage biopharmaceutical company translating genetic insights into the development of therapies for central nervous system (CNS) disorders characterized by neuronal excitation-inhibition imbalance, today shared positive topline results for its Phase 2, proof of concept study evaluating relutrigine in SCN2A and SCN8A developmental and epileptic encephalopathy (DEE) patients. “We are thrilled to see the combination of positive efficacy and tolerability of relutrigine for SCN2A and 8A, where there are no approved treatments. When comparing to the baseline rates, patients in EMBOLD had over 2,000 fewer seizures since the beginning of the study. This kind of remarkable impact keeps us focused on advancing our programs,” said Marcio Souza, president and chief executive officer. “Seizure freedom is the ultimate goal for patients, and we were humbled by the progress made with relutrigine during the EMBOLD study with over 30% of patients achieving this life-altering milestone. Most importantly, we are grateful to the patients, families, caregivers and clinicians who participated in the trial.” "With over 30 years of experience treating pediatric epilepsy, I am profoundly excited by the results we've seen in the EMBOLD Study. The meaningful reduction in seizures, with many patients experiencing a dramatic decrease, gives us real hope for improving the lives of these children” said Dr. Antonio Gil-Nagel, Director of the Epilepsy Program at the Ruber International Hospital and Principal Investigator for the EMBOLD Study. “Seeing over 30% of patients achieve seizure freedom and the remarkable improvements in their alertness and communication are especially encouraging. The magnitude of these results suggests that relutrigine could truly transform the landscape of pediatric epilepsy treatment”. “On behalf of the international SCN2A and SCN8A communities, whose loved ones face severe, life-threatening health challenges due to devastating seizures and the absence of approved treatments, we are optimistic about the initial results from EMBOLD. The achievement of significant reduction in seizures compared to placebo could represent a meaningful improvement in the lives of these children and their families. While early, the signals of seizure freedom and positive outcomes across multiple clinical assessments are also promising. We are very excited that the next phase of the study is already initiated, and we remain hopeful that this drug will prove to be a valuable therapy for our community, offering much-needed relief and hope,” said Kacie Craig, Gabi Conecker, Kris Pierce and Shawn Egan, in a joint statement from The Cute Syndrome Foundation, International SCN8A Alliance, SCN2A Australia, and the FamilieSCN2A Foundation. About the EMBOLD StudyEMBOLD is a multicenter, double-blind, placebo-controlled, intervention-period-masked, randomized study, followed by open-label extension (OLE), which enrolled eligible male and female participants aged 2-18 years with a diagnosis of early onset SCN2A-DEE or SCN8A-DEE. Sixteen patients were randomized (1:1) to receive relutrigine QD for 16 weeks, or relutrigine QD for 12 weeks and matching placebo QD for 4 weeks, administered orally or via gastrostomy/jejunostomy tube (G/J-tube). Fifteen patients were determined to be eligible for efficacy assessments.Dose adjustment was permitted to a maximum of 1.0 mg/kg/day and a minimum of 0.25 mg/kg/day.Thirteen patients enrolled in the open-label extension Summary of EMBOLD resultsRelutrigine was generally safe and well tolerated by patients during the EMBOLD study. Seven patients increased the daily dose from 0.5 to 1 mg/kg/day during the double-blind period of the study. No patient required dose reduction. The most common adverse events (AEs) were infections, vomiting, pyrexia, somnolence and constipation in patients receiving relutrigine. No patients discontinued due to an AE. Patients on relutrigine observed a placebo-adjusted reduction of 46% in countable motor seizures (log-transformed). Change in Global Impression of Improvement, assessed by the caregiver and clinician at week 16 for patients on relutrigine, showed an improvement (caregiver, clinician) in disruptive behavior (29%, 23%), communication (43%, 31%), seizure severity and intensity (71%, 62%) and alertness (57%, 69%). Eight patients have completed at least one 28-day period in the long-term extension of EMBOLD with a median reduction in motor seizures of 75%. Five patients achieved a 28-day seizure free status while receiving relutrigine, compared to none on placebo. Praxis to host a call on Tuesday, September 3 at 8:00 am ET to discuss the study results and next steps. To register for the call, please click here LINK The live webcast and replay will be available through the Events & Presentations page of the Investors and Media section of the company’s website at www.praxismedicines.com. About Relutrigine (PRAX-562) Relutrigine is a first-in-class small molecule in development for the treatment of developmental and epileptic encephalopathy (DEE) as a preferential inhibitor of persistent sodium current, shown to be a key driver of seizure symptoms in SCN2A-DEE and SCN8A-DEE. Relutrigine’s mechanism of sodium channel modulation is consistent with superior selectivity for disease state sodium channel (NaV) channel hyperexcitability. In vivo studies of relutrigine have demonstrated dose-dependent inhibition of seizures up to complete control of seizure activity in SCN2A, SCN8A and other DEE mouse models. Relutrigine has been generally well-tolerated in three Phase 1 studies and has demonstrated biomarker changes indicative of NaV channel blocking effects. Relutrigine has received Orphan Drug Designation (ODD) and Rare Pediatric Designation (RPD) from the FDA, and ODD from the European Medicines Agency for the treatment of SCN2A-DEE and SCN8A-DEE. To learn more about the EMBOLD study, please visit https://www.emboldstudy.org/. About Praxis  Praxis Precision Medicines is a clinical-stage biopharmaceutical company translating insights from genetic epilepsies into the development of therapies for CNS disorders characterized by neuronal excitation-inhibition imbalance. Praxis is applying genetic insights to the discovery and development of therapies for rare and more prevalent neurological disorders through our proprietary small molecule platform, Cerebrum™, and antisense oligonucleotide (ASO) platform, Solidus™, using our understanding of shared biological targets and circuits in the brain. Praxis has established a diversified, multimodal CNS portfolio including multiple programs across movement disorders and epilepsy, with four clinical-stage product candidates. For more information, please visit www.praxismedicines.com and follow us on Facebook, LinkedIn and Twitter/X.    Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws, including express or implied statements regarding Praxis’ future expectations, plans and prospects, or the clinical development of relutrigine, including with respect to the EMBOLD and related long-term extension study, the potential benefits of relutrigine to treat patients with aged 2-18 years with a diagnosis of early onset SCN2A-DEE or SCN8A-DEE and the potential impact to patients’ quality of life, as well as other statements containing the words “anticipate,” “believe,” “continue,” “could,” “endeavor,” “estimate,” “expect,” “anticipate,” “intend,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “seek,” “should,” “target,” “will” or “would” and similar expressions that constitute forward-looking statements under the Private Securities Litigation Reform Act of 1995. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation: uncertainties inherent in clinical trials; the expected timing of clinical trials, data readouts and the results thereof, and submissions for regulatory approval or review by governmental authorities; regulatory approvals to conduct trials; and other risks concerning Praxis’ programs and operations as described in its Annual Report on Form 10-K for the year ended December 31, 2023 and other filings made with the Securities and Exchange Commission. Although Praxis’ forward-looking statements reflect the good faith judgment of its management, these statements are based only on information and factors currently known by Praxis. As a result, you are cautioned not to rely on these forward-looking statements. 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