Praxis is taking a late-breaker slot at AES 2025 to unveil full results from RADIANT, reporting rapid seizure reductions in adults with treatment‑resistant epilepsy on vormatrigine, alongside open‑label extension data indicating sustained seizure reduction with relutrigine added to standard care. The company is also previewing translational and operational workstreams that could shape its registrational path: a drug–drug interaction profile for vormatrigine supporting broad combination use, preclinical analyses positioning relutrigine’s potency in Dravet‑relevant models, an emergency-use case combining an antisense oligonucleotide with precision sodium channel modulation in early‑onset SCN2A disease, and a large prospective observational effort to standardize seizure reporting and patient‑journey metrics.
The core event is a coordinated AES package spanning clinical readouts for two small‑molecule sodium channel modulators and program updates on the SCN2A‑targeting ASO, elsunersen. Beyond the late-breaker and open‑label extension, Praxis plans to detail its analysis framework for improving predictive validity across developmental and epileptic encephalopathy models (PAC‑DEE) and to introduce EMPOWER, a prospective, electronic record–integrated study aimed at strengthening real‑world seizure observation. Collectively, the slate signals a pivot from proof‑of‑concept signals to the reproducibility, combination‑use safety, and real‑world measurement infrastructure regulators and payers now expect.
Strategically, Praxis is leaning into precision epilepsy with two complementary modalities: functionally selective NaV modulation for broader epilepsy populations and an ASO with genotype‑specific intent for SCN2A gain‑of‑function disease. The late‑breaker indicates confidence in vormatrigine’s clinical effect size and onset kinetics, which, if confirmed, can differentiate in a market crowded with add‑on therapies that require slow titration and present interaction risk. Emphasizing a favorable drug–drug interaction profile is a deliberate positioning move to reduce exclusion criteria, enable polytherapy, and simplify protocol design. On the DEE side, highlighting preclinical potency relative to an approved Dravet therapy and an emergency‑use pediatric case is a message to regulators and investigators that the company is preparing the evidentiary bridge from models and N‑of‑1 learning to scalable trial designs. The observational EMPOWER study is the operational backbone of that strategy, building a common data layer for seizure frequency, severity, and context that can support endpoint selection, durability analyses, and potentially post‑marketing commitments.
For sites and CROs, the near‑term impact is practical. Adult focal and generalized epilepsy trials could become more accessible if DDI constraints are lighter, expanding eligibility and reducing washout complexity. DEE programs will continue to demand genetic confirmation and pediatric neurology infrastructure, including intrathecal administration for ASOs, specialized safety monitoring, and family‑centric consent workflows. Vendors focused on eDiary, EEG analytics, and data reconciliation should note Praxis’s intent to capture prospective, standardized seizure data at scale, a trend that can reduce variability but raises integration and adjudication demands. Regulators will scrutinize the company’s concordance framework and how it translates into responder rates, seizure‑free intervals, and durability across genotypes and age strata.
What matters next is the magnitude and consistency of the RADIANT dataset: responder distributions at clinically meaningful thresholds, time to effect, titration tolerability, and any interaction signals in polytherapy settings. Sustained benefit in the relutrigine extension, particularly maintenance of seizure freedom in defined SCN2A/SCN8A subgroups, will shape whether a single adequate and well‑controlled study plus supportive evidence can be negotiated or if a traditional two‑trial path is necessary. Watch for clarity on pediatric segmentation, alignment with FDA and EMA on endpoint selection, and whether EMPOWER’s real‑world data will be incorporated into natural history or external control strategies. The operational question is whether Praxis can stand up a genetic testing and pediatric site network at the pace implied by its AES footprint, and whether it moves to partner for late‑stage execution if the vormatrigine signal holds.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
