Praxis Precision Medicines, Inc., a biopharmaceutical firm in the clinical development phase, focuses on converting genetic knowledge into treatments for central nervous system (CNS) disorders marked by imbalances in neuron excitation and inhibition. The company has announced plans to present both preclinical and clinical findings from three of their epilepsy initiatives at the 2024 American Epilepsy Society (AES) Annual Meeting, scheduled for December 6-10 in Los Angeles, California.
“At Praxis, we stand on the verge of transformative innovation with our pioneering pipeline featuring relutrigine and vormatrigine, recognized as the most potent and selectively functional anti-seizure drugs crafted to date,” stated Steven Petrou, Praxis’ chief scientific officer and co-founder. “In light of encouraging outcomes from the relutrigine EMBOLD study in dealing with particularly difficult childhood epilepsies, we are optimistic that our upcoming therapies will reset the standards for DEEs as well as focal and broad-spectrum epilepsy treatments. At this year’s AES, we will unveil the newest progress across our epilepsy projects in an array of promising presentations.”
Relutrigine is an innovative small molecule for developmental and epileptic encephalopathies (DEEs), acting as a selective inhibitor of persistent sodium currents, a significant contributor to seizure symptoms in severe DEEs. Its mechanism precisely modulates sodium channels (NaV), aligning with enhanced specificity for hyperexcitable NaV channels in disease states. Animal model studies illustrate relutrigine’s dose-dependent seizure inhibition, achieving full seizure control in SCN2A, SCN8A, and other DEE models. It has shown a favorable safety profile in three Phase 1 trials and biomarker changes that suggest NaV channel modulation. Phase 2 EMBOLD trial data indicates a well-tolerated drug with considerable short- and long-term motor seizure improvements, with some patients achieving seizure freedom. The FDA has classified relutrigine as an Orphan Drug, and the European Medicines Agency has extended ODD for its effectiveness in treating SCN2A-DEE and SCN8A-DEE.
Vormatrigine is a next-gen, orally administered molecule developed for adult focal onset seizures and generalized epilepsy, specifically tackling the hyperexcitable state of NaV channels. Preclinical data sets it apart from existing treatments, indicating the potential to be top-tier for focal onset seizures. In vitro studies underscore its superior specificity for overactive NaV channels, while in vivo research confirms exceptional efficacy in the maximal electroshock seizure (MES) model, a key translational marker of focal epilepsy. The PRAX-628-101 study revealed that vormatrigine can be administered safely in humans at dosages over 15 times the projected effective rodent dose, suggesting a broad therapeutic window.
Elsunersen’s Clinical Development in Emergency Use: Cutting-edge ASO for SCN2A Developmental and Epileptic Encephalopathy Treatment. Elsunersen, an antisense oligonucleotide (ASO), aims to selectively lower SCN2A gene activity, addressing the root cause of seizures and other symptoms in patients with gain-of-function SCN2A mutations. Laboratory studies show reduced SCN2A gene activity and protein levels, while in vivo trials highlight reduced seizure incidence, improved behavior and movement, and enhanced survival in SCN2A models. The EMBRAVE investigation confirms elsenersen’s safety and sustained seizure reductions in SCN2A-DEE patients. The United States FDA and European Medicines Agency have recognized elsunersen with ODD, RPD, and PRIME designations for SCN2A-DEE treatment, with ongoing initiatives under alliance with Ionis Pharmaceuticals and RogCon, Inc.