Diana earned her PhD and PharmD with distinction in the field of Medicinal and Pharmaceutical Chemistry at the Universidade do Porto. She is an accomplished oncology scientist with 10+ years of experience in developing and managing R&D projects and research staff directed to the development of small proteins fit for medical use.
Dravet syndrome (DS) is a rare, lifelong condition that typically begins in the first year of life. It is characterized by uncontrolled, prolonged seizures, developmental delays, and cognitive impairment.1 While there is no cure for DS, ongoing clinical trials are exploring new treatments that could improve quality of life for those with the condition.
The ARGUS clinical trial (NCT04462770) is currently recruiting children and adults with DS to evaluate both the safety and efficacy of EPX-100 (clemizole hydrochloride) as adjunctive therapy in DS.2 EPX-100 is a modulator of serotonin signaling that has been shown to reduce seizures in patients with DS.1
This is a phase 2 global, multicenter, randomized 1:1, double-blind, placebo-controlled trial sponsored by Epygenix. The study will comprise a 4-week observational period followed by a 16-week double-blind period and a 3-year open-label extension. It uses matched placebo oral solution including color and taste dosed to match the active arm.2
A phase 3 clinical trial sponsored by Eisai Inc is currently recruiting patients with DS to assess the use of Belviq® (EPX-200, lorcaserin) as adjunctive therapy (NCT04572243, MOMENTUM 1).3 Like EPX-100, Belviq is a modulator of serotonin signaling.1
This trial aims to demonstrate that Belviq has superior efficacy in reducing the frequency of seizures in patients with DS when compared to a placebo. It is estimated to recruit 58 participants.3
Read more about DS experimental therapies
The active phase 2 clinical trial ENDYMION 1 (NCT03635073) sponsored by Takeda is a global, open-label extension assessing the long-term safety and tolerability of soticlestat when used with other antiseizure medications.4
Soticlestat is a selective inhibitor of cholesterol 24-hydroxylase (CH24H). The role of soticlestat’s inappropriate cholesterol metabolism is being studied in seizure-related CNS disorders. It was proven to reduce seizure burden, prevent sudden unexpected death in epilepsy (SUDEP), and protect against hyperthermia-induced seizure.1 Currently, the ENDYMION 1 trial has recruited 156 participants who will receive soticlestat twice per day.4
Read more about DS complications
In addition to the ENDYMION 1 study, soticlestat is also under evaluation in patients aged 2 to 21 years with DS. The SKYLINE trial (NCT04940624) is a phase 3 randomized, double-blind, placebo-controlled study with the goal of understanding if soticlestat is effective in reducing the number of convulsive seizures in children and young adult patients when used as an add-on therapy to standard antiseizure medication.5
Read more about DS prognosis
The ENDEAVOR trial (NCT05419492) is a phase 1/2, 2-part, multicenter study sponsored by Encoded Therapeutics that is designed to evaluate the safety and efficacy of ETX101 in participants aged 6 to 36 months with SCN1A-positive DS.6 ETX101 is a nonreplicating, recombinant adeno-associated viral vector serotype 9 (rAAV9) developed to promote the transcription of the SCN1A gene.6
The first part of the trial is an open-label, dose-escalation study, while the second part is a randomized, double-blind, sham delayed-treatment control, dose-selection study.6 This is the first clinical study of ETX101, and it is expected to recruit 22 participants.1,6 The administration of ETX101 will be performed via a single intracerebroventricular injection.1
The MONARCH clinical trial (NCT04442295) is a phase 2 study sponsored by Stoke Therapeutics Inc that is currently recruiting patients with DS to evaluate the safety and pharmacokinetics of single and multiple ascending doses of STK-001.1,7 The change in seizure frequency will also be observed as a secondary endpoint.7
STK-001 is an antisense oligonucleotide designed to increase SCN1A messenger RNA (mRNA) and consequently the expression of the Nav1.1 protein.7
Read more about DS genetics
Stoke Therapeutics is also sponsoring the SWALLOWTAIL clinical trial (NCT04740476) for the evaluation of the long-term safety and tolerability of repeated doses of STK-001 in patients with DS who have previously enrolled in other STK-001 studies.1,8 This is a multicenter, open-label, safety extension phase 2 study currently recruiting by invitation. It also aims to report overall clinical status and change in seizure frequency.8
1. Gao C, Pielas M, Jiao F, et al. Epilepsy in Dravet syndrome—current and future therapeutic opportunities. J Clin Med. 2023;12(7):2532. doi:10.3390/jcm12072532
2. EPX-100 (clemizole hydrochloride) as add-on therapy to control convulsive seizures in patients with Dravet syndrome (ARGUS). ClinicalTrials.gov. July 8, 2020. Updated March 22, 2023. Accessed March 30, 2023.
3. A study of lorcaserin as adjunctive treatment in participants with Dravet syndrome (MOMENTUM 1). ClinicalTrials.gov. October 1, 2020. Updated December 14, 2022. Accessed March 30, 2023.
4. A study of soticlestat in adults and children with rare epilepsies (Endymion 1). ClinicalTrials.gov. August 17, 2018. Updated May 13, 2022. Accessed March 30, 2023.
5. A study of soticlestat as an add-on therapy in children and young adults with Dravet syndrome. ClinicalTrials.gov. June 25, 2021. Updated March 8, 2023. Accessed March 30, 2023.
6. A clinical study to evaluate the safety and efficacy of ETX101 in infants and children with SCN1A-positive Dravet syndrome (ENDEAVOR). ClinicalTrials.gov. June 15, 2022. Accessed March 30, 2023.
7. An open-label study to investigate the safety of single and multiple ascending doses in children and adolescents with Dravet syndrome. ClinicalTrials.gov. June 22, 2020. Updated March 28, 2023. Accessed March 30, 2023.
8. An open-label extension study of STK-001 for patients with Dravet syndrome. ClinicalTrials.gov. February 5, 2021. Updated February 10, 2023. Accessed March 30, 2023.
Reviewed by Debjyoti Talukdar, MD, on 3/31/2023.