Synopulse Catalyst
Epilepsy & DEE Catalyst Report
October 2026
Monthly overview of epilepsy and developmental and epileptic encephalopathy (DEE) research, clinical data, regulatory and policy milestones, deals and funding, and the catalysts due next.
What we’re watching this month
Rapport Raised $432.5m in October, and Praxis Sets Out Its Relutrigine Launch on 12 November
Rapport Therapeutics raised the month's only epilepsy financing above $30m, and Stoke tied its zorevunersen NDA to cognition as well as seizures. November brings Lundbeck's results on 11 November and Praxis's investor day on 12 November, six weeks before relutrigine's 27 December FDA date.
October's money and regulatory work went to focal epilepsy and Dravet syndrome. Rapport Therapeutics raised $432.5m, eight days after RAP-219 met its primary endpoint in a Phase 2 bipolar mania trial, and will spend most of it on RAP-219's trials, led by the FOCUS Phase 3 programme in focal onset seizures. Stoke Therapeutics agreed its NDA plan for zorevunersen with the FDA, and Aurobindo won final approval for generic perampanel. We found no company Phase 2 or 3 epilepsy readout in the month; the clinical evidence came from 36-month VNS data, rescue-therapy analyses and the first LGS registry results.
Two Kv7 drugs and an AMPA modulator now chase cenobamate in focal epilepsy
Each challenger carries a different constraint. Xenon's azetukalner has been with the FDA since 17 September with no filing decision announced. Biohaven's opakalim has RISE 3 topline guided to the second half of 2026, but new enrolment has been paused since 4 September and the $350m licence to SK Biopharmaceuticals cleared US antitrust review only on 28 October.
Rapport has the fewest constraints. Its Epilepsia paper on 12 October, written with Johnson & Johnson scientists, put RAP-219's therapeutic index above 150 against motor impairment in mice, and the raise funds operations to the end of 2029. SK's cenobamate, the incumbent newer drug, enters Korean reimbursement on 1 November and has a US decision on an oral suspension on 31 January.
Three new focal-epilepsy drugs now have the cash or a partner to reach market; cenobamate's lead depends on how fast it widens access.
Stoke's Dravet filing rests on cognition, and its rivals report first
About 110 of EMPEROR's 162 primary patients were past the week-28 primary timepoint by 29 October, with none discontinued. The NDA will carry a combined Vineland-3 score next to seizure frequency, the evidence a disease-modification claim would need. Encoded's ETX101 and Harmony's EPX-100 both report Dravet data before EMPEROR's third-quarter 2027 readout, and Lundbeck finished randomising its Dravet trial of bexicaserin in September.
December is the next hard date
Praxis's relutrigine reaches its FDA action date on 27 December in SCN2A and SCN8A developmental and epileptic encephalopathies, and the company sets out launch readiness at its investor day on 12 November. Lundbeck guides DEEp OCEAN, the pivotal bexicaserin trial across DEEs including LGS, to late in the fourth quarter, and reports nine-month results on 11 November. The American Epilepsy Society meets in Denver from 4 to 8 December, inside the guidance windows for RISE 3, EMERALD and DEEp OCEAN.
Where we would change our mind
If RISE 3 reads out positively and SK closes the licence, opakalim becomes a funded late-stage rival to azetukalner with a hold on new enrolment still to clear. If RISE 3 misses, the next decisive focal-epilepsy data shift to Rapport's FOCUS programme, which the October raise now pays for.
Companies in this issue
- Angelini Pharma
- Aquestive Therapeutics
- Aurobindo Pharma
- Biogen
- Biohaven
- Catalyst Pharmaceuticals
- Encoded Therapeutics
- Eton Pharmaceuticals
- H. Lundbeck
- Harmony Biosciences
- Jazz Pharmaceuticals
- LivaNova
- Neurelis
- NeuroPace
- Praxis Precision Medicines
- Rapport Therapeutics
- Samjin Pharmaceutical
- SK Biopharmaceuticals
- SK Life Science
- Stoke Therapeutics
- UCB
- Xenon Pharmaceuticals
$432.5m
raised by Rapport Therapeutics on 28 October, the month's only epilepsy financing above $30m
6
research and clinical evidence items from October, from RAP-219's preclinical paper to 36-month VNS data
4
regulatory and access decisions: an FDA-aligned NDA plan, a generic approval and two Korean pricing and reimbursement moves
3
FDA action dates in the next five months: relutrigine, cenobamate suspension and LIBERVANT
Moves that matter
A $432.5m raise in focal epilepsy, a cognition-led NDA plan in Dravet and a new rival in seizure rescue led October
Rapport Therapeutics (RAPP)RAP-219, a γ8 AMPA receptor negative modulator
$432.5m raised on 28 October. Funded through the end of 2029
| Event | Asset | Indication | Timing | Comment |
|---|---|---|---|---|
| Phase 2 bipolar mania topline | RAP-219, 0.75 mg once daily | Bipolar mania | 20 Oct 2026 | 253 patients; 3.1-point placebo-adjusted YMRS gain at week 3, p=0.045. Phase 3 to start 2H 2027. |
| Offerings priced | RAP-219 | Focal onset seizures; bipolar mania | 28 Oct 2026 | $205.0m stock, $25.0m warrants, $172.5m notes, $30.0m placement. Proceeds mainly for RAP-219 trials. |
| Preclinical paper, Epilepsia | RAP-219 | Focal epilepsy models | 12 Oct 2026 | Therapeutic index above 150 against motor impairment in mice; J&J scientists co-authored. |
| FOCUS 1 and FOCUS 2 Phase 3 | RAP-219 | Drug-resistant focal onset seizures | Enrolling | No topline date given; runway extends past the readouts. |
| CompetitorNDA submitted 17 Sep; FDA filing decision pending | Azetukalner, Kv7 opener; Xenon Pharmaceuticals (XENE) | Focal seizures | Pending | First of the new mechanisms to file. |
| CompetitorRISE 3 topline | Opakalim, Kv7 activator; Biohaven (BHVN), licensed to SK Biopharmaceuticals | Focal onset seizures | 2H 2026 | New enrolment paused since 4 Sep; licence awaits closing after the 28 Oct antitrust clearance. |
| CompetitorKorean reimbursement; US oral suspension decision | Cenobamate; SK Biopharmaceuticals | Focal seizures | 1 Nov 2026; 31 Jan 2027 | The incumbent newer drug widens access in its home market. |
CI Intel Rapport now has the money to finish focal epilepsy Phase 3 without a partner, and its cash outlasts the readouts. The $432.5m, raised eight days after a narrow Phase 2 win in bipolar mania, pays for FOCUS 1 and 2 and two bipolar Phase 3 trials and runs to the end of 2029. Its rivals in adjunctive focal epilepsy each carry a constraint: Xenon's azetukalner is waiting on an FDA filing decision, Biohaven's opakalim has new enrolment on hold and a licence still to close, and SK's cenobamate is only now reimbursed in Korea. Our read is that RAP-219 no longer needs a partner to reach a filing, but the bipolar programme will compete with epilepsy for the same cash and attention. Watch RISE 3 before year end and Xenon's filing decision. Sources: Rapport pricing release, 28 Oct 2026; Rapport 8-K, 30 Oct 2026; Rapport bipolar release, 20 Oct 2026; Biohaven Q3 2026 results; Xenon NDA release, 17 Sep 2026. Checked 31 October 2026. | ||||
Stoke Therapeutics (STOK)zorevunersen, with Biogen outside the US, Canada and Mexico
NDA plan aligned on 5 October. EMPEROR readout in Q3 2027
| Event | Asset | Indication | Timing | Comment |
|---|---|---|---|---|
| FDA meeting on the planned NDA | Zorevunersen, antisense oligonucleotide | Dravet syndrome | 5 Oct 2026 | Four Vineland-3 subdomains averaged into one score, next to major motor seizure frequency at week 28. |
| EMPEROR progress at Q3 results | Zorevunersen | Dravet syndrome | 29 Oct 2026 | All 162 primary patients past week 8, about 110 past week 28, none discontinued; China cohort of 5 enrolled in October. |
| NDA data submissions; readout; NDA complete | Zorevunersen | Dravet syndrome | 1H 2027; Q3 2027; 2H 2027 | $358.8m of cash at 30 Sep, guided to fund operations into early 2028. |
| Potential US approval and launch | Zorevunersen | Dravet syndrome | Early 2028 | Company guidance. |
| CompetitorENDEAVOR Part 1B initial data | ETX101, AAV gene therapy; Encoded Therapeutics (private) | Dravet syndrome | Q4 2026 | Pivotal Part 2 dosed its first patient in May. |
| CompetitorARGUS Phase 3 topline | EPX-100 (clemizole); Harmony Biosciences (HRMY) | Dravet syndrome | 1H 2027 | LIGHTHOUSE in LGS reads out in the same half. |
| CompetitorDEEp SEA randomisation complete | Bexicaserin; H. Lundbeck | Dravet syndrome | 15 Sep 2026 | More than 100 patients aged 2 to 65. |
CI Intel Stoke is building its NDA on cognition and behaviour as well as seizures, and the trial is now mostly past its primary timepoint. With about 110 of 162 patients past week 28 and no dropouts, EMPEROR's risk now sits in the effect size rather than retention. The Vineland-3 composite is the evidence a disease-modification claim would need. Encoded's one-time ETX101 and Harmony's oral EPX-100 both report Dravet data before EMPEROR, so Stoke will be compared on seizures first. Watch Encoded's Part 1B data in the fourth quarter and the start of Stoke's rolling NDA in the first half of 2027. Sources: Stoke release, 5 Oct 2026; Stoke Q3 2026 results, 29 Oct 2026; Encoded release, 6 May 2026; Harmony Q2 2026 results; Lundbeck release, 15 Sep 2026. Checked 31 October 2026. | ||||
Eton Pharmaceuticals (ETON); Aquestive Therapeutics (AQST)LIBERVANT (diazepam) buccal film, against Neurelis's Valtoco
US rights licensed on 13 October. Launch guided to April 2027
| Event | Asset | Indication | Timing | Comment |
|---|---|---|---|---|
| Exclusive US licence and 20-year supply deal | LIBERVANT | Seizure clusters | 13 Oct 2026 | $10.0m upfront; up to $47.5m in milestones; mid-teens royalties on US net sales. |
| Valtoco orphan exclusivity ends | LIBERVANT | Ages 2 to 5 and 12 and over | 10 Jan 2027 | Full approval for these ages becomes possible; tentative approval held today. |
| FDA action date, ages 6 to 11 | LIBERVANT | Seizure clusters | 29 Mar 2027 | Type 9 NDA under review. |
| US launch | LIBERVANT | Seizure clusters | April 2027 | Subject to final approval. |
| CompetitorPost hoc data at the Child Neurology Society | Valtoco (diazepam nasal spray); Neurelis | Seizure clusters, ages 2 to 17 | 15 Oct 2026 | 266 status epilepticus episodes; 73.3% ended before 30 minutes; 92.5% needed one dose. |
CI Intel Seizure rescue is about to gain a buccal film, and the incumbent nasal spray is already defending with data. Aquestive kept manufacturing and took $10m upfront rather than launching LIBERVANT itself, which puts a specialty commercial company against Neurelis's Valtoco from April 2027. Neurelis used the Child Neurology Society to show Valtoco ending most status epilepticus episodes within clusters on a single dose, the claim a buccal film will have to match. Our read is that the contest turns on paediatric labelling: LIBERVANT's 6 to 11 decision on 29 March decides whether it can be offered from age 2 upward at launch. Sources: Eton and Aquestive release, 14 Oct 2026; Aquestive 8-K, 14 Oct 2026; Neurelis release, 15 Oct 2026. Checked 31 October 2026. | ||||
News by stage
- Discovery
- Clinic entry
- Readouts
- Regulatory
- Access
- Deals
- Funding
Rapport published RAP-219's preclinical selectivity data, written with Johnson & Johnson scientists
Company announcements only; journal-only academic studies are left out. Papers are dated by first online publication.
| Date | Company or institution | Event | Asset | Indication | Notes |
|---|---|---|---|---|---|
| Preclinical results | |||||
| Rapport Therapeutics (RAPP) | Preclinical results: RAP-219 paper co-authored with J&J scientists | RAP-219, γ8 AMPA receptor negative modulator | Focal epilepsy | Epilepsia. Kindled-mouse ED50 about 0.05 mg/kg single dose and 0.02 mg/kg multiple dose; therapeutic index above 150 against rotarod impairment. Moves that matter #1 | |
CI noteThe paper sets out the selectivity case Rapport will need in FOCUS against Kv7 openers with known CNS side effects. | |||||
- Discovery
- Clinic entry
- Readouts
- Regulatory
- Access
- Deals
- Funding
VNS cut seizures by a median 76% at 36 months, while only 4% of treatments reported to an LGS registry stopped all seizures
No Phase 1 or Phase 1/2 data are included, and journal-only outcome studies with no company or competitor link are left out. October brought no company Phase 2 or 3 epilepsy readout; these rows are post hoc analyses of Phase 3 data, long-term device data and a patient registry.
| Date | Company or institution | Event | Asset | Indication | Notes |
|---|---|---|---|---|---|
| Device and drug evidence | |||||
| LivaNova (LIVN) | CORE-VNS 36-month results published | VNS Therapy | Drug-resistant epilepsy, focal onset seizures | Neuromodulation. 426 completed 36 months: median seizure reduction 76%, 64% responders, 16% seizure free; LivaNova release 23 Oct. | |
CI noteHospitalisation fell from 27% to 7%, the outcome payers weigh against newer drugs and responsive neurostimulation. | |||||
| UCB, with Robert-Debré Hospital | Post hoc analysis ties fenfluramine dose to more seizure-free days | Fenfluramine (Fintepla) | Lennox-Gastaut syndrome | Epilepsia. Gains over placebo p<.0001; seizure-free days tracked seizure frequency closely but CGI-I only weakly. | |
| Neurelis | Post hoc data: Valtoco ended most status epilepticus episodes within clusters | Valtoco (diazepam nasal spray) | Seizure clusters, ages 2 to 17 | Child Neurology Society. 266 episodes; 73.3% ended before 30 minutes; 92.5% needed one dose. Moves that matter #3 | |
| Angelini Pharma, with Marche Polytechnic University | BLESS interim: quality of life stable on adjunctive cenobamate | Cenobamate (Ontozry) | Focal onset seizures | Epilepsia. 377 adults over 52 weeks; clinicians rated 85.7% to 91.3% improved. | |
| Patient registries | |||||
| LGS Foundation | First LGS-CORE registry data: 4% of reported treatments stopped all seizures | – | Lennox-Gastaut syndrome | NORD Summit poster, 26 Oct; 104 medicines reported. 40% take four or more medicines; 27% have needed emergency care. | |
CI noteCaregiver data, uncontrolled; it frames the unmet need that bexicaserin and EPX-100 will be judged against. | |||||
- Discovery
- Clinic entry
- Readouts
- Regulatory
- Access
- Deals
- Funding
Two regulatory moves: an FDA-aligned NDA plan for zorevunersen and a generic perampanel approval
| Date | Company or institution | Event | Asset | Indication | Notes |
|---|---|---|---|---|---|
| Approvals | |||||
| Aurobindo Pharma | FDA: final ANDA approval, generic perampanel | Perampanel tablets, 2 to 12 mg | Partial-onset seizures; adjunctive PGTCS | Reference drug Fycompa, held by Catalyst Pharmaceuticals. Launch guided for October to December 2026. | |
| FDA pathway | |||||
| Stoke Therapeutics (STOK) | FDA: meeting aligned the planned NDA | Zorevunersen, antisense oligonucleotide | Dravet syndrome | Vineland-3 composite of four subdomains set for EMPEROR. NDA data through 1H 2027; readout Q3 2027. Moves that matter #2 | |
- Discovery
- Clinic entry
- Readouts
- Regulatory
- Access
- Deals
- Funding
Korea listed cenobamate for reimbursement and raised the price of a lorazepam injection with a single domestic supplier
| Date | Company or institution | Event | Asset | Indication | Notes |
|---|---|---|---|---|---|
| Korea | |||||
| Ministry of Health and Welfare, Korea | Raises lorazepam injection price to keep supply | Lorazepam injection, Samjin Pharmaceutical | Status epilepticus; paediatric seizures | 804 won to 5,682 won from 1 Nov under the shortage-prevention list; single domestic manufacturer. | |
| Ministry of Health and Welfare, Korea | Lists cenobamate for national health insurance from 1 November | Xcopri (cenobamate), SK Biopharmaceuticals | Drug-resistant focal epilepsy | Seven years after US approval; patients had imported it. Price not disclosed. Moves that matter #1 | |
CI noteSK's home-market listing comes as two Kv7 drugs and RAP-219 move toward the same adjunctive focal-seizure patients. | |||||
- Discovery
- Clinic entry
- Readouts
- Regulatory
- Access
- Deals
- Funding
The $350m Kv7 licence cleared US antitrust review but has not closed
Eton’s LIBERVANT licence from Aquestive ($10m upfront, $57.5m with milestones) sits below the $25m upfront threshold and is covered in Moves that matter.
| Date | Company or institution | Event | Asset | Indication | Notes |
|---|---|---|---|---|---|
| Licensing | |||||
| Biohaven (BHVN); SK Biopharmaceuticals | US antitrust waiting period expired on the Kv7 licence | Opakalim (BHV-7000) and Kv7 platform | Focal epilepsy | Upfront $350m at closing and $50m a year later; up to $150m in milestones plus royalties. Closing still pending. Moves that matter #1 | |
- Discovery
- Clinic entry
- Readouts
- Regulatory
- Access
- Deals
- Funding
Rapport's $432.5m raise was October's only epilepsy financing above $30m
| Date | Company or institution | Event | Asset | Indication | Notes |
|---|---|---|---|---|---|
| Public offerings | |||||
| Rapport Therapeutics (RAPP) | Prices stock, pre-funded warrant and convertible note offerings with a private placement | RAP-219 | Focal onset seizures; bipolar mania | $205.0m stock, $25.0m warrants, $172.5m 2.25% notes due 2032, $30.0m placement; options exercised; closed 30 Oct. Moves that matter #1 | |
Catalyst calendar
Praxis sets out relutrigine’s launch on 12 November, six weeks before its 27 December FDA date, as three DEE readouts are guided to the fourth quarter
Exact dates come from the company, the regulator or the meeting organiser; quarter and half-year entries are company guidance. FDA action dates carry a slate bar. Entries dated 1 to 4 November fall before publication.
| Timing | Company | Catalyst | Drug | Indication | What to look for |
|---|---|---|---|---|---|
| November 2026 | |||||
| 1 Nov | Ministry of Health and Welfare, Korea | Cenobamate coverage and lorazepam price change take effect | Xcopri; lorazepam injection | Focal epilepsy; status epilepticus | Look for the cenobamate upper price once published. |
| 2 Nov | Jazz Pharmaceuticals (JAZZ) | Third-quarter results | Epidiolex | LGS, Dravet, TSC seizures | Epidiolex sales trend; any update on the KCNT1 programme bought with Actio. |
| 3 to 5 Nov | International Bureau for Epilepsy | European Epilepsy Summit, Brussels, 4 Nov | – | – | Launch of the European Epilepsy Barometer 2026 on care and access. |
| 4 Nov | Harmony Biosciences (HRMY) | Third-quarter results | EPX-100 (clemizole) | Dravet syndrome; LGS | Whether ARGUS and LIGHTHOUSE stay guided to 1H 2027. |
| 9 Nov | Praxis Precision Medicines (PRAX) | Third-quarter results | Relutrigine; vormatrigine | DEEs; focal seizures | EMERALD timing and the POWER2 restart. |
| 11 Nov | H. Lundbeck | Results for the first nine months | Bexicaserin | DEEs including LGS | Whether DEEp OCEAN stays guided to late Q4 2026. |
| 12 Nov | Praxis Precision Medicines (PRAX) | Investor Day, New York | Relutrigine | SCN2A and SCN8A DEEs | Launch readiness ahead of the 27 Dec FDA action date. |
| 12 Nov | NeuroPace (NPCE) | Third-quarter results | RNS System | Drug-resistant epilepsy | Update on the PMA supplement for idiopathic generalised epilepsy. |
| Fourth quarter 2026, no fixed date | |||||
| Late Q4 2026 | H. Lundbeck | DEEp OCEAN headline results | Bexicaserin | DEEs including LGS | Randomisation completed in July. |
| Q4 2026 | Praxis Precision Medicines (PRAX) | EMERALD topline | Relutrigine | Broad DEEs | About 200 patients enrolled. |
| Q4 2026 | Praxis Precision Medicines (PRAX) | POWER2 restart and POWER3 start | Vormatrigine | Focal onset seizures | |
| Q4 2026 | Encoded Therapeutics (private) | ENDEAVOR Part 1B initial data | ETX101 | Dravet syndrome, ages 4 to 18 | |
| Q4 2026 | Rapport Therapeutics (RAPP) | Open-label safety data; China Phase 3 recruitment starts | RAP-219 | Focal onset seizures | |
| 2H 2026 | Biohaven (BHVN) | RISE 3 topline | Opakalim (BHV-7000) | Focal onset seizures | Reconfirmed 29 Oct; new enrolment paused since 4 Sep. |
| Pending | Biohaven (BHVN); SK Biopharmaceuticals | Closing of the Kv7 licence | Opakalim | Focal epilepsy | $350m due at closing. |
| Pending | Xenon Pharmaceuticals (XENE) | FDA filing decision on the NDA submitted 17 Sep | Azetukalner | Focal seizures | No acceptance or PDUFA date announced yet. |
| Oct to Dec 2026 | Aurobindo Pharma | US launch of generic perampanel | Perampanel | Partial-onset seizures | |
| December 2026 | |||||
| 4 to 8 Dec | American Epilepsy Society | Annual Meeting, Denver | – | – | Inside the guidance windows for RISE 3, EMERALD and DEEp OCEAN. |
| 27 Dec | Praxis Precision Medicines (PRAX) | FDA action date | Relutrigine | SCN2A and SCN8A DEEs | Extended after a major amendment. |
| 2027 | |||||
| 10 Jan | Aquestive Therapeutics (AQST); Eton | Valtoco orphan exclusivity ends; LIBERVANT eligible for full approval | LIBERVANT | Seizure clusters, ages 2 to 5 and 12 and over | |
| 31 Jan | SK Life Science | FDA action date, cenobamate oral suspension | Cenobamate | Focal seizures, adults | |
| 29 Mar | Aquestive Therapeutics (AQST); Eton | FDA action date, ages 6 to 11 | LIBERVANT | Seizure clusters | |
| Apr 2027 | Eton Pharmaceuticals (ETON) | US launch | LIBERVANT | Seizure clusters | Subject to final approval. |
| 1H 2027 | Stoke Therapeutics (STOK) | NDA data submissions | Zorevunersen | Dravet syndrome | |
| 1H 2027 | Harmony Biosciences (HRMY) | ARGUS and LIGHTHOUSE Phase 3 topline | EPX-100 (clemizole) | Dravet syndrome; LGS | PDUFA dates anticipated in 2028. |
| 1H 2027 | Rapport Therapeutics (RAPP) | Phase 3 start | RAP-219 | Primary generalised tonic-clonic seizures | |
| Q3 2027 | Stoke Therapeutics (STOK) | EMPEROR Phase 3 readout | Zorevunersen | Dravet syndrome | About 110 of 162 patients past week 28 by 29 Oct. |
| 2H 2027 | Stoke Therapeutics (STOK) | NDA submission complete | Zorevunersen | Dravet syndrome | |
| End 2027 | Encoded Therapeutics (private) | ENDEAVOR Part 2 initial data | ETX101 | Dravet syndrome, ages 6 months to 4 years | |
| 2027 | Praxis Precision Medicines (PRAX) | EMBRAVE3 topline | Elsunersen | Early-onset SCN2A DEE | |
| 2028 | |||||
| Early 2028 | Stoke Therapeutics (STOK) | Potential US approval and launch | Zorevunersen | Dravet syndrome | Company guidance. |