RARE Daily

EMA Grants Praxis’ Elsunersen PRiME Designation in Rare Epilepsy

November 16, 2023

Rare Daily Staff

The European Medicines Agency granted Praxis Precision Medicines Priority Medicines (PRiME) designation for elsunersen, its experimental therapy for the treatment of SCN2A gain of function developmental and epileptic encephalopathy.

The EMA’s PRiME designation provides enhanced development support for priority medicines that target an unmet need and 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.

SCN2A developmental and epileptic encephalopathy (SCN2A-DEE) is a debilitating monogenic epilepsy disorder caused by a variant in the SCN2A gene, associated with early mortality. The SCN2A gene is critical in the formation of sodium channel proteins in the brain, which control the flow of sodium ions into neurons. This movement of sodium ions is a major component of generating electrical signals called action potentials, the way in which the cells communicate.

SCN2A-DEE is characterized by a broad spectrum of phenotypes. Early-onset SCN2A-DEE presents before three months and can lead to profound impact on patients, including drug-resistant seizures, significant cognitive impairment, movement disorders such as dystonia or ataxia and problems in other body systems such as gastrointestinal or ocular. Currently there are no approved treatments for SCN2A-DEE, and the standard-of-care typically involves a regimen of many concurrent anti-seizure medications as well as medications to manage co-morbidities. Despite these interventions, more than 70 percent of early-onset SCN2A-DEE patients live with uncontrolled seizures, and approximately 75 percent live with severe intellectual disability with patients rarely surviving beyond their teenage years.

Elsunersen is an antisense oligonucleotide (ASO) designed to selectively decrease SCN2A gene expression, directly targeting the underlying cause of early-seizure-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, with potential to be the first disease-modifying treatment for SCN2A-DEE.

Elsunersen has received Orphan Drug designation and Rare Pediatric Disease designation from the U.S. Food and Drug Adminstration, and Orphan Drug designation from the EMA for the treatment of SCN2A-DEE. The elsunersen program is ongoing under a collaboration with Ionis Pharmaceutics and RogCon.

Part 1 of the EMBRAVE study is an open-label cohort involving pediatric patients aged 2 to18 years. These patients, diagnosed with early-onset SCN2A developmental and epileptic encephalopathy, are administered elsunersen over a period of up to 13 weeks. The primary objective is to determine the safety and tolerability of intrathecal delivery of elsunersen.

“Elsunersen has the potential to significantly impact the lives of patients with SCN2A-DEE and their families,” said Marcio Souza, president and CEO of Praxis. “We welcome the recognition by the EMA of not only the unmet need in the condition, but the breakthrough potential of elsunersen.”

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