FDA Extends Relutrigine Review, Delays PDUFA to December

The FDA has extended its review of Praxis Precision Medicines' New Drug Application (NDA) for relutrigine, an investigational therapy for SCN2A- and SCN8A-related developmental and epileptic encephalopathy (DEE), by three months. The agency classified additional sensitivity analyses of existing clinical data that Praxis submitted as a major amendment, moving the target action date from September 27, 2026, to December 27, 2026.¹

The original PDUFA date would have fallen this weekend; the extension was announced in late June, well before that date arrived, so no FDA decision on relutrigine is expected in the coming days. Praxis said the major-amendment classification stemmed from the additional analyses alone, not from a request for new clinical studies, and that the FDA raised no safety or manufacturing concerns in connection with the extension.

“Relutrigine has demonstrated a compelling profile, and we have every confidence in the strength of the data package to benefit patients with SCN2A and SCN8A DEEs," Marcio Souza, president and chief executive officer of Praxis, said in a statement.¹

Mid-cycle review clears without new concerns

In an August 2026 corporate update, Praxis said the FDA had completed its mid-cycle review meeting for relutrigine and identified no major safety or efficacy concerns to date, and that no advisory committee meeting is planned ahead of the December decision. The company said it is advancing launch preparations, including hiring commercial and medical leadership, building inventory, establishing a patient support program, and engaging payers ahead of a potential approval.²

Regulatory path to the NDA

The FDA accepted relutrigine's NDA and granted priority review in March 2026, weeks after Praxis submitted NDAs for both relutrigine and ulixacaltamide, a separate investigational therapy for essential tremor, in February 2026.³ Relutrigine holds breakthrough therapy designation from the FDA, granted in June 2025, and from the European Medicines Agency, along with orphan drug designation from both agencies and rare pediatric disease designation from the FDA covering SCN2A-DEE, SCN8A-DEE, and Dravet syndrome; the pediatric designation would make Praxis eligible for a priority review voucher if relutrigine is approved.

READ MORE: Xenon Submits New Drug Application for Azetukalner as Treatment for Focal Seizures

Relutrigine is a first-in-class, small-molecule preferential inhibitor of persistent sodium current, designed to selectively dampen the disease-state channel hyperexcitability that drives seizures in SCN2A- and SCN8A-DEE without broadly suppressing normal neuronal sodium channel activity.

The efficacy data behind the NDA

The NDA rests primarily on EMBOLD, a registrational study in patients with SCN2A- and SCN8A-DEE. In the study's registrational cohort of 51 patients, relutrigine produced a 53% placebo-adjusted reduction in motor seizure frequency over 16 weeks (P <.0002) and a 66% increase in motor seizure-free days (P =.034), with caregiver- and clinician-reported functional improvements in behavior, alertness, and communication reaching statistical significance (P ≤.002) across multiple scales. An independent data monitoring committee recommended stopping the registrational cohort early after determining the efficacy threshold had been met; no drug-related serious adverse events were reported, and treatment-related adverse events were predominantly mild to moderate.^4,5

These results built on an earlier, smaller EMBOLD cohort of 16 randomized patients, reported in September 2024, in which relutrigine produced a 46% placebo-adjusted reduction in motor seizures over 16 weeks and more than 30% of patients achieved seizure freedom during a 28-day assessment window. In that cohort's open-label extension, patients receiving relutrigine had a median 75% reduction in motor seizure rate, and 5 patients achieved seizure freedom, building on the phase 2 EMBOLD results first reported from that cohort's double-blind period.⁶

“The meaningful reduction in seizures gives us real hope for improving lives of these children,” Antonio Gil-Nagel, MD, PhD, co-head of the neurology department and chief of the epilepsy program at Hospital Ruber Internacional in Madrid, Spain, said at the time of the released data.⁶

Looking ahead

Beyond SCN2A- and SCN8A-DEE, Praxis is also running EMERALD, a broader trial of relutrigine across more than 50 distinct genetic etiologies of developmental and epileptic encephalopathy that has enrolled approximately 200 patients, exceeding the company's original target. Topline results are expected in the fourth quarter of 2026 and, if positive, could support a supplemental NDA submission in 2027.²

REFERENCES
1. Praxis Precision Medicines announces extension period for relutrigine for treatment of SCN2A and SCN8A developmental and epileptic encephalopathies. News release. Praxis Precision Medicines, Inc. Published June 29, 2026. Accessed September 25, 2026. https://investors.praxismedicines.com/news-releases/news-release-details/praxis-precision-medicines-announces-extension-period/
2. Praxis Precision Medicines provides corporate update and reports second quarter 2026 financial results. News release. Praxis Precision Medicines, Inc. Published August 6, 2026. Accessed September 25, 2026. https://investors.praxismedicines.com/news-releases/news-release-details/praxis-precision-medicines-provides-corporate-update-and-20
3. Praxis Precision Medicines announces FDA acceptance and priority review of new drug application for relutrigine in patients with SCN2A and SCN8A DEEs. News release. Praxis Precision Medicines, Inc. Published March 30, 2026. Accessed September 25, 2026. https://www.globenewswire.com/news-release/2026/03/30/3264996/0/en/praxis-precision-medicines-announces-fda-acceptance-and-priority-review-of-new-drug-application-for-relutrigine-in-patients-with-scn2a-and-scn8a-dees.html
4. Praxis AES wrap-up: best-in-class potential across rare pediatric and adult epilepsies. News release. Praxis Precision Medicines, Inc. Published December 8, 2025. Accessed September 25, 2026. https://www.globenewswire.com/news-release/2025/12/08/3201478/0/en/Praxis-AES-Wrap-up-Best-in-Class-Potential-Across-Rare-Pediatric-and-Adult-Epilepsies.html
5. Praxis Precision Medicines announces positive results from EMBOLD study for relutrigine in SCN2A and SCN8A developmental and epileptic encephalopathies. News release. Published December 4, 2025. Accessed September 25, 2026. https://www.globenewswire.com/news-release/2025/12/04/3200330/0/en/praxis-precision-medicines-announces-positive-results-from-embold-study-for-relutrigine-in-scn2a-and-scn8a-developmental-and-epileptic-encephalopathies.html
6. Praxis Precision Medicines announces positive topline results from the EMBOLD study in SCN2A and 8A developmental epilepsies, highlighting the disease-modifying potential of relutrigine. News release. Published September 3, 2024. Accessed September 25, 2026. https://investors.praxismedicines.com/news-releases/news-release-details/praxis-precision-medicines-announces-positive-topline-results-0