PRAX relutrigine

SCN2A/SCN8A epileptic encephalopathies · Praxis · NDA

Of 100 applications in this same position, about 80 get approved.

Until the FDA deadline83d

Base rate76%

Gap+4pts

PDUFA target date 2026-12-27the FDA may act earlier or later

Summary

FDA approval of relutrigine in this review cycle is put at 80%, above the 76% base rate for first-time applications from smaller companies. In the registrational cohort of the EMBOLD study the drug cut seizures by 53% against placebo (p<0.0002), and the study stopped early for efficacy. Praxis reports priority review, a mid-cycle meeting with no major safety or efficacy concerns, no advisory committee and a clean sponsor inspection. Four things hold the estimate down: the evidence is one small study with an unusual control (a single 4-week placebo period in 25 of 53 children); FDA took three extra months to review added sensitivity analyses; few patients have been exposed; and the contract manufacturers are not named.

Recorded 2026-10-05 08:21 UTC · v1Proof ↓

Evidence · 10 items

Why 80%, not 76%

Indication

SCN2A and SCN8A developmental and epileptic encephalopathies (DEEs)

76% of comparable applications were approved in the past: the opponent every forecast has to beat. Below are the reasons this forecast differs.

▲ supports approval, ▼ counts against it. More squares, more weight.

01▲ SupportsMedium The registrational cohort met its primary endpoint by a wide margin

In the registrational cohort (cohort 2) of the EMBOLD study, relutrigine reduced monthly motor seizures by 53% relative to placebo over 16 weeks (p<0.0002). The interim analysis that stopped the study was to be tested at a 4% significance level, so the result cleared its threshold with room to spare. Key secondary endpoints were also significant: motor seizure-free days rose 66.2% (p=0.0340), and the clinician and caregiver global impression scores favoured relutrigine (-2.62, p<0.0001; -3.7, p=0.002). The first cohort, run under the same design at a lower starting dose, showed a 46% placebo-adjusted reduction (p=0.0354; 15 patients on relutrigine, 7 placebo periods). More than 80% of patients were already taking sodium channel blockers at baseline. Praxis says the effect was consistent in SCN2A and SCN8A patients; subgroup figures are not public.

Source: EMBOLD poster, American Epilepsy Society meeting, December 2025 (Kamireddy et al.): https://praxismedicines.com/wp-content/uploads/2025/12/Gil-Nagel_AES2025_EMBOLD-Topline.pdf; Praxis 8-K, 2025-12-08: https://www.sec.gov/Archives/edgar/data/1689548/000168954825000114/prax-20251204.htm; Praxis press release, 2025-11-04: https://www.globenewswire.com/news-release/2025/11/04/3180282/0/en/praxis-announces-accelerated-development-path-for-relutrigine-in-scn2a-and-scn8a-dee-patients-following-positive-fda-feedback.html; Praxis corporate presentation, August 2026: https://www.sec.gov/Archives/edgar/data/1689548/000168954826000082/praxiscorporatedeckaugus.htm
02▲ SupportsSmall FDA agreed in advance that this one study could support the application

Praxis reported on 4 November 2025 that, after a Type B meeting and written advice on the protocol and statistical analysis plan, it had reached alignment with FDA that the ongoing EMBOLD study could serve as the basis of substantial evidence of effectiveness, and that FDA agreed a positive interim analysis could serve as the basis of the NDA. FDA had granted Breakthrough Therapy Designation in July 2025 on the first cohort and its 11-month open-label follow-up. After the interim result, a further discussion with FDA in December 2025 led the company to confirm it would file. These are the company's accounts; FDA's meeting minutes are not public.

Source: Praxis press release, 2025-11-04: https://www.globenewswire.com/news-release/2025/11/04/3180282/0/en/praxis-announces-accelerated-development-path-for-relutrigine-in-scn2a-and-scn8a-dee-patients-following-positive-fda-feedback.html; Praxis 8-K exhibit 99.1, 2025-11-05: https://www.sec.gov/Archives/edgar/data/1689548/000168954825000110/praxisq32025pr.htm; Praxis 8-K, 2025-07-17: https://www.sec.gov/Archives/edgar/data/1689548/000168954825000086/prax-20250717.htm; Praxis 8-K, 2025-12-11: https://www.sec.gov/Archives/edgar/data/1689548/000168954825000116/prax-20251209.htm
03▲ SupportsSmall Review signals reported so far are favourable

FDA accepted the application for priority review (announced 30 March 2026). On 6 August 2026 Praxis said the mid-cycle meeting was complete, that FDA had identified no major safety or efficacy concerns to date, and that the agency confirmed no advisory committee meeting is planned; FDA's advisory committee calendar shows no meeting on the drug. An FDA inspection of the sponsor under the Bioresearch Monitoring programme, covering data integrity and the statistical and interim analyses, ended with no Form 483. Two limits: these are the sponsor's summaries, and the mid-cycle statement says nothing about manufacturing.

Source: Praxis press release, 2026-03-30: 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; Praxis 8-K, 2026-04-06: https://www.sec.gov/Archives/edgar/data/1689548/000168954826000031/prax-20260406.htm; Praxis 8-K exhibit 99.1, 2026-08-06: https://www.sec.gov/Archives/edgar/data/1689548/000168954826000082/praxisq22026pr.htm; Praxis 10-Q filed 2026-08-06: https://www.sec.gov/Archives/edgar/data/1689548/000168954826000083/prax-20260630.htm; FDA advisory committee calendar, viewed 2026-10-05: https://www.fda.gov/advisory-committees/advisory-committee-calendar
04▼ AgainstSmall A small study with an unusual control

Only 53 children were randomized in the registrational cohort, against a planned 80, because the study stopped at the interim analysis. There was no parallel placebo group. Every patient was assigned to relutrigine; 25 were also assigned one blinded 4-week placebo period within the 16 weeks. The placebo-adjusted result therefore compares time on relutrigine in 51 patients with a single 4-week placebo period in 25 patients, most of whom also count among the 51. The agreed primary analysis was an ANCOVA on log-transformed seizure counts with treatment as the only stated factor. Not public: where in the 16 weeks the placebo period fell, and how carry-over from earlier dosing, or a rebound after stopping the drug, was handled. PubMed lists no peer-reviewed report of the results; the public record is a conference poster and company releases.

Source: EMBOLD poster, December 2025: https://praxismedicines.com/wp-content/uploads/2025/12/Gil-Nagel_AES2025_EMBOLD-Topline.pdf; Praxis press release, 2025-11-04: https://www.globenewswire.com/news-release/2025/11/04/3180282/0/en/praxis-announces-accelerated-development-path-for-relutrigine-in-scn2a-and-scn8a-dee-patients-following-positive-fda-feedback.html; ClinicalTrials.gov NCT05818553: https://clinicaltrials.gov/study/NCT05818553; PubMed search for relutrigine / PRAX-562 on 2026-10-05, including the review at https://doi.org/10.3390/cimb48080830
05▼ AgainstSmall FDA took three extra months to review added analyses of the efficacy data

On 29 June 2026 FDA moved the goal date from 27 September to 27 December 2026 after Praxis submitted additional sensitivity analyses of existing clinical data, which FDA deemed a major amendment. Praxis said no new studies were requested and no safety or manufacturing concerns were cited. According to TD Cowen, as reported by Fierce Biotech, the company described the submission as simple and limited to minor sensitivity analyses and changes to how data were formatted and presented; what the analyses tested is not public. An extension is not usually bad news. FDA's user-fee commitments list a major re-analysis of submitted studies as a typical major amendment and say an extension should, "except in rare circumstances", be used when the new information could lead to approval in the current cycle. Jefferies, cited by BioSpace, counts more than 80% of extended reviews ending in approval, and Rhythm's setmelanotide supplement was approved in March 2026 after an extension for the same stated reason. Still, it shows FDA wanted more than the original package on the one study the application rests on. Only one extension is allowed per cycle; 27 December 2026 is a Sunday.

Source: Praxis 8-K, 2026-06-29: https://www.sec.gov/Archives/edgar/data/1689548/000168954826000069/prax-20260629.htm; Fierce Biotech, 2026-06-30: https://www.fiercebiotech.com/biotech/praxis-faces-fda-delay-analysts-point-finger-agency-layoffs; BioSpace, 2026-06-30: https://www.biospace.com/fda/fda-hits-praxis-with-3-month-delay-for-epilepsy-drug-verdict; PDUFA performance goals FY2023-2027, section I.A.5: https://www.fda.gov/media/151712/download; Rhythm Pharmaceuticals press release, 2026-03-19: https://www.sec.gov/Archives/edgar/data/1649904/000162828026019995/ex991hopdufapressrelease.htm
06▼ AgainstSmall Few patients have been exposed

The blinded safety data cover 67 children: 16 in the first cohort and 51 in the registrational cohort, each for up to 16 weeks. Long-term results reported so far cover 13 patients followed for 11 months. Two phase 1 studies in healthy adults enrolled 112 and 48 participants. EMERALD, a larger placebo-controlled study in about 200 patients with epileptic encephalopathies of any cause, is still blinded, and how much of its safety data FDA has received is not public. In the registrational cohort one death and one withdrawal of consent are listed as discontinuations on placebo. The poster's counts (53 randomized, 51 in the relutrigine safety analysis) suggest both patients left before receiving relutrigine; the cause of death is not public, and Praxis says no serious adverse event was drug-related. This is a thin base for a new chemical entity meant for long-term use in children, though Praxis reports that FDA raised no major safety concern at mid-cycle.

Source: EMBOLD poster, December 2025: https://praxismedicines.com/wp-content/uploads/2025/12/Gil-Nagel_AES2025_EMBOLD-Topline.pdf; American Epilepsy Society abstract 1.38, December 2025: https://aesnet.org/abstractslisting/relutrigine-demonstrates-sustained-seizure-reduction-with-continued-exposure-on-top-of-standard-of-care-results-from-the-embold-open-label-extension; phase 1 posters: https://praxismedicines.com/wp-content/uploads/2023/09/IEC2023_562-101_Final_QRcode.pdf and https://praxismedicines.com/wp-content/uploads/2023/09/IEC2023_562-102_Final_QRcode.pdf; Praxis 8-K exhibit 99.1, 2026-08-06: https://www.sec.gov/Archives/edgar/data/1689548/000168954826000082/praxisq22026pr.htm; ClinicalTrials.gov NCT07010471: https://clinicaltrials.gov/study/NCT07010471
07▲ SupportsSmall Reported tolerability is clean

In the registrational cohort the commonest adverse events occurred at similar or lower exposure-adjusted rates on relutrigine than on placebo (per 100 patient-months: pyrexia 11.74 vs 13.35; somnolence 9.13 vs 13.35; diarrhoea 4.57 vs 8.90), with upper respiratory infection higher on relutrigine (9.79 vs 4.45). Praxis reports no drug-related serious adverse events, no dose reductions, and no clinically significant findings in vital signs, laboratory tests or ECGs; one patient stopped for an adverse event during a relutrigine period. The ongoing EMERALD study excludes patients with familial short QT syndrome, Brugada syndrome and certain arrhythmias, which shows cardiac conduction is a monitored risk; no cardiac signal has been reported. No REMS has been mentioned in company disclosures.

Source: EMBOLD poster, December 2025: https://praxismedicines.com/wp-content/uploads/2025/12/Gil-Nagel_AES2025_EMBOLD-Topline.pdf; Praxis corporate presentation, August 2026: https://www.sec.gov/Archives/edgar/data/1689548/000168954826000082/praxiscorporatedeckaugus.htm; ClinicalTrials.gov NCT07010471: https://clinicaltrials.gov/study/NCT07010471
08▲ SupportsSmall No approved therapy, and FDA has been approving rare neurological drugs on single small trials

No drug is approved for SCN2A or SCN8A developmental and epileptic encephalopathy; relutrigine holds orphan drug and rare paediatric disease designations. In February 2026 FDA's commissioner and a senior deputy wrote that one pivotal trial plus confirmatory evidence is now the agency's default expectation. On 3 September 2026 FDA approved zilganersen, the first drug for Alexander disease, on one randomized trial of 49 patients. These describe the climate at FDA, not this review team's reading of this study.

Source: Praxis 8-K exhibit 99.1, 2026-08-06: https://www.sec.gov/Archives/edgar/data/1689548/000168954826000082/praxisq22026pr.htm; BioPharma Dive, 2026-02-19: https://www.biopharmadive.com/news/fda-makary-prasad0one-pivotal-trial-nejm/812557/; FDA press release, 2026-09-03: https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-alexander-disease
09▼ AgainstSmall Manufacturing cannot be checked from outside

Praxis owns no manufacturing sites and relies on contract manufacturers for drug substance, drug product and packaging. None is named for relutrigine in its filings, so no inspection record (Form 483, warning letter or classification) can be looked up, and there is no public record of whether pre-approval inspections have taken place. It would be the company's first approved product. On the other side, the product is a small molecule in an oral liquid, simpler than a biologic or a sterile injectable; Praxis says FDA cited no manufacturing concerns when it extended the review, that the supply chain is established and that launch inventory is being built.

Source: Praxis 10-K filed 2026-02-19 (Manufacturing; Risk Factors): https://www.sec.gov/Archives/edgar/data/1689548/000168954826000029/prax-20251231.htm; Praxis 8-K, 2026-06-29: https://www.sec.gov/Archives/edgar/data/1689548/000168954826000069/prax-20260629.htm; Praxis 8-K exhibit 99.1, 2026-08-06: https://www.sec.gov/Archives/edgar/data/1689548/000168954826000082/praxisq22026pr.htm; Q2 2026 results call transcript, 2026-08-06: https://www.fool.com/earnings/call-transcripts/2026/08/13/praxis-prax-q2-2026-earnings-call-transcript/
10▲ SupportsSmall The company is preparing to launch and is not short of cash

Praxis says the relutrigine commercial and medical teams are hired and trained, launch inventory is being built, and a patient support programme and payer discussions are under way. It reported $1.4 billion in cash and investments at 30 June 2026, enough by its estimate to fund operations into 2028, so its financing does not hinge on this approval. It made inducement grants to 66 new employees on 1 September and 14 on 1 October 2026. On 6 August it said it would give no further regulatory updates before the action dates, and it has filed no 8-K since (as of 5 October 2026), so the silence carries no information. Launch spending shows the company's confidence, not FDA's view: every favourable account of the review comes from the sponsor.

Source: Praxis 8-K exhibit 99.1, 2026-08-06: https://www.sec.gov/Archives/edgar/data/1689548/000168954826000082/praxisq22026pr.htm; Q2 2026 results call transcript, 2026-08-06: https://www.fool.com/earnings/call-transcripts/2026/08/13/praxis-prax-q2-2026-earnings-call-transcript/; Praxis press releases, 2026-09-03 and 2026-10-02: https://www.globenewswire.com/news-release/2026/09/03/3356230/0/en/praxis-precision-medicines-inc-announces-inducement-grants-under-nasdaq-listing-rule-5635-c-4.html and https://www.globenewswire.com/news-release/2026/10/02/3374007/0/en/praxis-precision-medicines-inc-announces-inducement-grants-under-nasdaq-listing-rule-5635-c-4.html; SEC EDGAR filing list for Praxis Precision Medicines (CIK 1689548)

What would change this forecast

01
Down: Praxis discloses a manufacturing or facility-inspection problem, or says FDA has asked for further analyses or data.
02
Down: the EMERALD study in broader epileptic encephalopathies, due to report in the fourth quarter of 2026, fails or shows a new safety signal before FDA acts.
03
Down: FDA schedules an advisory committee meeting, or the goal date passes with no action and no explanation.
04
Up: Praxis discloses that labeling discussions are complete, or that manufacturing-site inspections closed without findings.
05
Up: EMERALD reports a positive result, with safety in line with EMBOLD, before FDA acts.
06
Void rather than no: Praxis withdraws the application before FDA acts.

Any change is published as a new version; earlier versions stay exactly as they were.

Confidence

Medium

Manufacturing and inspection risk

Medium

Relutrigine is a small molecule given as an oral liquid, by mouth or feeding tube, a simpler product than a biologic or a sterile injectable. Praxis owns no manufacturing sites and relies on contract manufacturers for drug substance, drug product and packaging. None is named for relutrigine in its filings, so their FDA inspection records cannot be checked, and there is no public record of whether pre-approval inspections have taken place. It would be the company's first approved product; the annual report filed in February 2026 said Praxis had not yet manufactured a commercial-scale product. In its favour, Praxis says FDA cited no manufacturing concerns when it extended the review in June 2026, and that the supply chain is established and launch inventory is being built. The company's summary of the mid-cycle meeting mentions safety and efficacy only. What cannot be judged: who the manufacturers are, their compliance status, and whether any manufacturing questions are open.

Record · version 1

Written on 2026-10-05, 83 days before the PDUFA target date.

Timeline

Versions

v1 2026-10-05 08:21 UTC 80% Current version JSON ↓.ots ↓ ○ Timestamp submitted, awaiting block confirmation

Fingerprint

SHA-2562e77111737a42e39ff46201250edb3e350cca13e3bdf78b9f6727ca3db78949f

The fingerprint of the v1 file. It is what the timestamp commits to: change one character of the file and the fingerprint no longer matches.

Verify it yourself

Download the JSON file above and the .ots file of the same name into one folder.
Compute the SHA-256 of the file. It should match the fingerprint above.
Verify with OpenTimestamps. Once the timestamp is in a Bitcoin block, ots verify reports the block time if you run a Bitcoin node; without one, drop both files on the verifier at opentimestamps.org, or run ots info to see the block height and look it up in any block explorer. If the block time is before the FDA’s decision, the file cannot have been written afterwards.

pip install opentimestamps-client
shasum -a 256 v1_20261005T082133Z.json
ots verify v1_20261005T082133Z.json.ots
ots info v1_20261005T082133Z.json.ots

Scoring rule

What is scored is the last version recorded at least 2 days before the PDUFA target date; if the FDA decides early, only versions recorded before the day of its decision count. For this forecast the cutoff is 2026-12-25. Its error (also called the Brier score) is the squared distance between the forecast and the outcome, set against the error of quoting the base rate only.