Dravet syndrome: Research & Drug Discovery Data

Drug discovery

drugs

With orphan designations

Overview

Dravet syndrome is a severe developmental and epileptic encephalopathy caused predominantly by SCN1A mutations (85% of cases), characterized by refractory seizures onset in infancy, prolonged febrile seizures, and diverse seizure types evolving with age. Key features include developmental delays, intellectual disability, motor impairments, and comorbidities like sleep disorders and autonomic dysfunction. Treatment focuses on seizure control while avoiding sodium channel blockers, with emerging gene-targeted therapies in clinical trials [1][5][6][17].

Population

Incidence: 1:15,700–40,900 births; prevalence 1.5–6.5 per 100,000 [2][4][7].
Typically caused by de novo SCN1A mutations; rare autosomal dominant inheritance [1][12].
Mortality: 3.7–20.8% (SUDEP, status epilepticus) [4][9][14].

Burden

Patient: Developmental delay (100%), motor deficits (e.g., crouched gait), recurrent status epilepticus [1][6][17].
Caregiver: 47–70% report depression; $19,000–$20,000 annual productivity loss [4][9].
Economic: Mean direct costs up to $77,914/year; inpatient care drives expenses [4][10].

Therapies

First-line: Valproate ± clobazam/stiripentol [1][5][8].
FDA-approved adjuncts: Fenfluramine, cannabidiol [6][8]; ketogenic diet/VNS for refractory cases [1][8].
Avoid: Sodium channel blockers (e.g., carbamazepine, lamotrigine) [1][6].

Categories: rare genetic diseases, rare neurological diseases

Research Papers

1,146 drug discovery papers about Dravet syndrome, with 2 first-in-class and 66 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:

2026-07-06 | Perampanel in Chinese patients with Dravet syndrome: Efficacy and tolerability assessed via a multicenter, prospective, real-world observational study.

As a third-generation antiseizure medication, the efficacy of perampanel in treating Dravet syndrome (DS) remains incompletely characterized. This multicenter, prospective, real-world observational study aimed to evaluate the efficacy and long-term tolerability of perampanel as adjunctive therapy in Chinese patients with DS. Patients with unresolved DS were enrolled from four participating hospitals in China between January 2019 and December 2023. All patients received perampanel as add-on therapy. Efficacy and retention rate were evaluated at 3, 6, and 12 months of perampanel treatment. Genetic screening for SCN1A mutations was performed in all enrolled patients. Fifty-six patients were enrolled, of whom 48 (85.71%) harbored SCN1A mutations. The mean treatment duration of perampanel was 25.00 ± 7.65 months, with a mean maximum daily perampanel dose of 3.94 ± 1.19 mg. The retention rates at 6 and 12 months were 69.64% and 64.29%, respectively. After 6 and 12 months of treatment, the ≥50% responder rates were 66.07% and 60.71%, while seizure-freedom rates were 21.43% and 12.50%, respectively. Seizure exacerbation occurred in three patients (5.36%). Adverse events occurred in six patients during treatment (three discontinued treatment), with no new safety concerns identified. Among 30 patients with ≥50% seizure frequency reduction throughout 12-month treatment who carried SCN1A mutations, 33.33% had truncating mutations, 46.67% had missense mutations, 13.33% had splice site mutations, 3.33% had in-frame mutations, and 3.33% had large chromosomal deletions encompassing SCN1A. No significant difference in the ≥50% seizure frequency reduction rate was observed between patients with SCN1A truncating mutations and those with missense mutations. Additionally, treatment response to perampanel did not differ significantly according to the specific mutation regions within the Nav1.1 sodium channel. Perampanel demonstrated favorable efficacy and acceptable long-term tolerability as adjunctive therapy in Chinese patients with DS. The efficacy of perampanel remained consistent regardless of the specific genotype or location of SCN1A mutations.

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2026-07-05 | Prolonged fenfluramine use in open-label studies of Dravet or Lennox-Gastaut syndromes: Long-term safety, tolerability, patient global functioning, and considerations for interpreting effectiveness.

Long-term safety and global functioning are reported in patients with Dravet syndrome (DS) or Lennox-Gastaut syndrome (LGS) treated with fenfluramine in an open-label extension (OLE) study after participating in a previous open-label feeder study. Patients could enroll in this international, multicenter OLE (NCT03936777) after completing one of three fenfluramine open-label studies. The latest feeder study fenfluramine dose was continued, then flexibly titrated (maximum: .7 mg/kg/day [26 mg/day] without stiripentol or .4 mg/kg/day [17 mg/day] with stiripentol), with ≥1 concomitant antiseizure medication administered. Primary endpoint was fenfluramine long-term safety/tolerability. Global functioning using caregiver- and investigator-reported Clinical Global Impression of Improvement (CGI-I) ratings, globally and for subdomains (cognition, behavior, motor function), at last visit relative to study baseline was evaluated. Overall treatment exposure and age groups were analyzed post hoc. A total of 412 patients enrolled (DS: 265 [64.3%], LGS: 147 [35.7%]); 30.8% were ≥18 years old. Median fenfluramine treatment duration in this OLE was 729.5 days (range = 8-1544), and overall median fenfluramine exposure, including feeder studies, was 1464.5 days (range = 171-2800). In this OLE, ≥1 treatment-emergent adverse event (TEAE) was reported in 311 (75.5%) patients; fenfluramine-related (per investigator) serious TEAEs were reported in five (1.2%) patients. Three patients died in this OLE (deemed unrelated to fenfluramine by investigators). After starting this OLE already receiving fenfluramine, 373 of 401 (93.0%) and 376 of 401 (93.8%) patients were rated by caregiver and investigator, respectively, as "improved or no change" on CGI-I versus this study baseline; subdomain ratings of "improved or no change" were largely consistent with global assessment. In our OLE study of patients with DS or LGS treated with fenfluramine (up to 4 years), no new or unexpected safety signals were observed; global functioning was improved or stable (vs. study baseline) in >90% of patients, supporting long-term fenfluramine use in pediatric and adult patients with DS or LGS.

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2026-06-23 | Effectiveness and tolerability of fenfluramine in pediatric and adult patients with developmental and epileptic encephalopathies: A multicenter, retrospective, real-world clinical-practice study.

Developmental and epileptic encephalopathies (DEEs) are characterized by drug-resistant seizures and developmental slowing/regression. We examined the efficacy and tolerability of fenfluramine (FFA) in pediatric and adult patients with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and other DEEs. In this multicenter, retrospective, real-world study, FFA treatment was initiated ≥12 months before database closure. Data from patients' charts at 3, 6 and 12 months were recorded in the Spanish Epilepsy Society's DEEs registry. Effectiveness endpoints included seizure reductions of 100%, ≥75%, and ≥50% (responder), median percent seizure reduction, and seizure worsening. Safety endpoints included adverse event (AE) rates. The study included 166 patients (LGS, n = 84; DS, n = 42; other DEE, n = 40; mean age 16.6 ± 12.1 years [111 pediatric, median 10.1 years; 55 adult, median 26.5 years]). Patients had a median of 3 prior failed anti-seizure medications (ASMs). At 12 months, the median FFA dose was 0.49 mg/kg/day, with 77.1% treatment retention. There was a 68.8% median reduction in seizure frequency between baseline and 12 months (p < .001), with significant reductions across all diagnostic groups (LGS, p < .001; DS, p < .001; other DEE, p = .004). The 12-month ≥50% responder rate was 61%, with no statistically significant differences according to age. At 12 months, there were significant reductions in the mean number of concomitant ASMs (p = .004) and the proportion of patients requiring rescue medication (p < .001). Meaningful improvements in Clinical Global Impression scores for cognition (59.3% of patients), behavior (40.9%), sleep (24.3%), and caregiver (44.8%) domains were observed. At 12 months, AEs were reported in 68.1% of patients (mostly mild-to-moderate) and AEs leading to discontinuation in 12%, with no significant differences according to age. FFA was effective, with predictable tolerability, in patients with different DEEs and seizure types, supporting its use as an effective treatment option in pediatric and adult patients with DEEs.

Open article ↗

2026-07-06 | Perampanel in Chinese patients with Dravet syndrome: Efficacy and tolerability assessed via a multicenter, prospective, real-world observational study.

Open article ↗

2026-07-05 | Prolonged fenfluramine use in open-label studies of Dravet or Lennox-Gastaut syndromes: Long-term safety, tolerability, patient global functioning, and considerations for interpreting effectiveness.

Open article ↗

2026-06-23 | Effectiveness and tolerability of fenfluramine in pediatric and adult patients with developmental and epileptic encephalopathies: A multicenter, retrospective, real-world clinical-practice study.

Open article ↗

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Drug Discovery Landscape

27 orphan drug designations for Dravet syndrome, including 5 approved therapies.

Drug	Therapy type	Regulator	Orphan designation	Approval	Sponsor
chemically modified oligonucleotide designed as an ADAR-recruiting guide RNA	oligonucleotides	FDA	2025-04-16	—	RecoRNA (Guangzhou) Biotechnology Co., Ltd.
(R)-N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide	small molecules	FDA	2025-01-16	—	iQure Pharma Inc
bexicaserin hydrochloride (bexicaserin)	small molecules	FDA	2024-09-17	—	Longboard Pharmaceuticals, Inc.
Adeno-associated virus serotype 9 expressing a transcription factor for the SCN1A gene	gene therapies	EMA	2023-05-22	—	Pharma Gateway AB
small molecule agonist of 5-hydroxytryptamine serotonergic receptors	small molecules	FDA	2022-07-27	—	Xenon Pharmaceuticals Inc.
18‐mer antisense oligonucleotide complementary to SCN1A mRNA, sodium salt	oligonucleotides	EMA	2022-02-24	—	Biogen Netherlands B.V.
2-[(3-Methylbutyl)amino]-1,4-naphthalenedione	small molecules	FDA	2021-10-12	—	Neuroene Therapeutics
Lorcaserin hydrochloride	small molecules	EMA	2021-03-26	—	Premier Research Group S.L.
Lorcaserin	small molecules	FDA	2020-08-31	—	Eisai Inc.
non-replicating recombinant adeno associated viral vector, serotype 9, designed to promote increased transcription of SCN1A gene	gene therapies	FDA	2020-05-14	—	Encoded Therapeutics
18-mer antisense oligonucleotide complementary to SCN1A mRNA	oligonucleotides	FDA	2019-08-05	—	Stoke Therapeutics, Inc.
diazepam	small molecules	FDA	2018-05-23	—	Xeris Pharmaceutical, Inc.
cannabidiol	small molecules	FDA	2017-12-21	—	AXIUM Pharmaceuticals, Inc.
cholesterol 24S-hydroxylase inhibitor	small molecules	FDA	2017-11-29	—	Takeda Development Center Americas, Inc.
trazodone	small molecules	FDA	2017-08-18	—	Epygenix Therapeutics, Inc.
clemizole	small molecules	FDA	2017-04-19	—	Epygenix Therapeutics, Inc.
lorcaserin	small molecules	FDA	2017-04-17	—	Epygenix Therapeutics, Inc.
Huperzine A	small molecules	FDA	2017-04-12	—	Supernus Pharmaceuticals, Inc.
synthetic, single stranded, fully phosphorothioated 2¿-OMethyl-RNA and DNA mixmer oligonucleotide-based compound targeted against natural antisense transcripts (NATs)	oligonucleotides	FDA	2017-03-16	—	Camp4 Therapeutics
26 base synthetic single-stranded fully phosphorothioated 2'-O-methyl-RNA and DNA mixmer oligonucleotide-based compound	oligonucleotides	EMA	2017-02-27	—	S-cubed Pharmaceutical Services ApS
Cannabidiol [Epidyolex]	small molecules	EMA	2014-10-15	2019-09-23	Jazz Pharmaceuticals Ireland Limited
cannabidiol	small molecules	FDA	2014-07-01	—	Insys Development Company, Inc.
fenfluramine HCI [Fintepla]	small molecules	FDA	2013-12-20	2020-06-25	UCB, Inc.
Fenfluramine hydrochloride [Fintepla]	small molecules	EMA	2013-12-18	2020-12-21	UCB Pharma
cannabidiol [Epidiolex]	small molecules	FDA	2013-11-14	2018-09-28	Jazz Pharmaceuticals Research UK Limited
stiripentol [Diacomit]	small molecules	FDA	2008-10-30	2018-08-20	Biocodex
Clonazepam Intranasal Spray	small molecules	FDA	2007-12-19	—	Jazz Pharmaceuticals, Inc.

Dravet syndrome

Dravet syndrome

Dravet syndrome

Overview

Population

Burden

Therapies

Categories: rare genetic diseases, rare neurological diseases

Research Papers

2026-07-06 | Perampanel in Chinese patients with Dravet syndrome: Efficacy and tolerability assessed via a multicenter, prospective, real-world observational study.

2026-07-05 | Prolonged fenfluramine use in open-label studies of Dravet or Lennox-Gastaut syndromes: Long-term safety, tolerability, patient global functioning, and considerations for interpreting effectiveness.

2026-06-23 | Effectiveness and tolerability of fenfluramine in pediatric and adult patients with developmental and epileptic encephalopathies: A multicenter, retrospective, real-world clinical-practice study.

2026-07-06 | Perampanel in Chinese patients with Dravet syndrome: Efficacy and tolerability assessed via a multicenter, prospective, real-world observational study.

2026-07-05 | Prolonged fenfluramine use in open-label studies of Dravet or Lennox-Gastaut syndromes: Long-term safety, tolerability, patient global functioning, and considerations for interpreting effectiveness.

2026-06-23 | Effectiveness and tolerability of fenfluramine in pediatric and adult patients with developmental and epileptic encephalopathies: A multicenter, retrospective, real-world clinical-practice study.

Drug Discovery Landscape

Updated: Aug 22, 2026