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Soticlestat as an adjunctive therapy in children and young adults with Dravet syndrome.

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Title: Soticlestat as an adjunctive therapy in children and young adults with Dravet syndrome.
Authors: Sullivan, Joseph (AUTHOR), Valente, Kette (AUTHOR), Villanueva, Vicente (AUTHOR), Strzelczyk, Adam (AUTHOR), Nabbout, Rima (AUTHOR), Nakagawa, Eiji (AUTHOR), Zhang, Yuehua (AUTHOR), Zolnowska, Marta (AUTHOR), Khan, Yasir (AUTHOR), Dong, Cheng (AUTHOR), Hsiao, Samuel (AUTHOR), Sheikh, Sarah I. (AUTHOR), von Rosenstiel, Philipp (AUTHOR), Asgharnejad, Mahnaz (AUTHOR), Murthy, Venkatesha (AUTHOR)
Source: Epilepsia (Series 4). Jun2026, Vol. 67 Issue 6, p2796-2807. 12p.
Subjects: Anticonvulsants, Treatment effectiveness, Childhood epilepsy, Clinical trials, Young adults, Safety, Seizures (Medicine)
Abstract: Objective: This study evaluated the efficacy, safety, and tolerability of soticlestat as adjunctive therapy in children and young adults with Dravet syndrome (DS). Methods: SKYLINE (NCT04940624) was a multicenter, randomized, double‐blind, placebo‐controlled, phase 3 trial that enrolled patients with DS aged 2–21 years with uncontrolled convulsive seizures (≥4/month despite adequate treatment). Participants received oral soticlestat 300 mg (weight adjusted) or matching placebo twice daily. The total study duration was 16 weeks, comprising 4‐week dose titration and 12‐week maintenance treatment periods. The primary endpoint was a comparison of monthly convulsive seizure frequency between baseline and the titration/maintenance periods. Key secondary endpoints included several modified Caregiver and Clinical Global Impression of Improvement (GI‐I) scales for DS. Results: One hundred forty‐four participants were randomized (71 placebo, 73 soticlestat) with a mean (SD) age of 10.3 (5.0) years; 72 (50%) were male, and 117 (81.3%) were receiving ≥3 antiseizure medications. Median change from baseline in convulsive seizure frequency over the full treatment period was −8.64% with placebo (n = 71) and −22.16% with soticlestat (n = 73), a difference of −15.64% (p =.061); in the maintenance treatment period, these changes were −11.99% with placebo and −23.29% with soticlestat, a difference of −14.29% (p =.089). The proportion of participants with ≥50% reduction in convulsive seizures was 9.9% with placebo and 27.4% with soticlestat (nominal p =.008). Soticlestat showed clinically meaningful results in the Caregiver and Clinical GI‐I, and Clinical GI‐I Seizure Intensity and Duration scales over the 16‐week treatment period (all nominal p‐values ≤.004). The most commonly reported treatment‐emergent adverse events related to study drug were somnolence, change in seizure presentation, decreased appetite, and insomnia. Significance: Although statistical significance was narrowly missed, soticlestat showed a numerical benefit over placebo for convulsive seizure decrease. Clinically meaningful benefits across multiple secondary endpoints were observed. No new safety concerns emerged. [ABSTRACT FROM AUTHOR]
Copyright of Epilepsia (Series 4) is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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PubTypeId: academicJournal
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  Data: Soticlestat as an adjunctive therapy in children and young adults with Dravet syndrome.
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  Data: <searchLink fieldCode="AR" term="%22Sullivan%2C+Joseph%22">Sullivan, Joseph</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Valente%2C+Kette%22">Valente, Kette</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Villanueva%2C+Vicente%22">Villanueva, Vicente</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Strzelczyk%2C+Adam%22">Strzelczyk, Adam</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Nabbout%2C+Rima%22">Nabbout, Rima</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Nakagawa%2C+Eiji%22">Nakagawa, Eiji</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhang%2C+Yuehua%22">Zhang, Yuehua</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zolnowska%2C+Marta%22">Zolnowska, Marta</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Khan%2C+Yasir%22">Khan, Yasir</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Dong%2C+Cheng%22">Dong, Cheng</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hsiao%2C+Samuel%22">Hsiao, Samuel</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sheikh%2C+Sarah+I%2E%22">Sheikh, Sarah I.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22von+Rosenstiel%2C+Philipp%22">von Rosenstiel, Philipp</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Asgharnejad%2C+Mahnaz%22">Asgharnejad, Mahnaz</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Murthy%2C+Venkatesha%22">Murthy, Venkatesha</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Epilepsia+%28Series+4%29%22">Epilepsia (Series 4)</searchLink>. Jun2026, Vol. 67 Issue 6, p2796-2807. 12p.
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  Data: <searchLink fieldCode="DE" term="%22Anticonvulsants%22">Anticonvulsants</searchLink><br /><searchLink fieldCode="DE" term="%22Treatment+effectiveness%22">Treatment effectiveness</searchLink><br /><searchLink fieldCode="DE" term="%22Childhood+epilepsy%22">Childhood epilepsy</searchLink><br /><searchLink fieldCode="DE" term="%22Clinical+trials%22">Clinical trials</searchLink><br /><searchLink fieldCode="DE" term="%22Young+adults%22">Young adults</searchLink><br /><searchLink fieldCode="DE" term="%22Safety%22">Safety</searchLink><br /><searchLink fieldCode="DE" term="%22Seizures+%28Medicine%29%22">Seizures (Medicine)</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: Objective: This study evaluated the efficacy, safety, and tolerability of soticlestat as adjunctive therapy in children and young adults with Dravet syndrome (DS). Methods: SKYLINE (NCT04940624) was a multicenter, randomized, double‐blind, placebo‐controlled, phase 3 trial that enrolled patients with DS aged 2–21 years with uncontrolled convulsive seizures (≥4/month despite adequate treatment). Participants received oral soticlestat 300 mg (weight adjusted) or matching placebo twice daily. The total study duration was 16 weeks, comprising 4‐week dose titration and 12‐week maintenance treatment periods. The primary endpoint was a comparison of monthly convulsive seizure frequency between baseline and the titration/maintenance periods. Key secondary endpoints included several modified Caregiver and Clinical Global Impression of Improvement (GI‐I) scales for DS. Results: One hundred forty‐four participants were randomized (71 placebo, 73 soticlestat) with a mean (SD) age of 10.3 (5.0) years; 72 (50%) were male, and 117 (81.3%) were receiving ≥3 antiseizure medications. Median change from baseline in convulsive seizure frequency over the full treatment period was −8.64% with placebo (n = 71) and −22.16% with soticlestat (n = 73), a difference of −15.64% (p =.061); in the maintenance treatment period, these changes were −11.99% with placebo and −23.29% with soticlestat, a difference of −14.29% (p =.089). The proportion of participants with ≥50% reduction in convulsive seizures was 9.9% with placebo and 27.4% with soticlestat (nominal p =.008). Soticlestat showed clinically meaningful results in the Caregiver and Clinical GI‐I, and Clinical GI‐I Seizure Intensity and Duration scales over the 16‐week treatment period (all nominal p‐values ≤.004). The most commonly reported treatment‐emergent adverse events related to study drug were somnolence, change in seizure presentation, decreased appetite, and insomnia. Significance: Although statistical significance was narrowly missed, soticlestat showed a numerical benefit over placebo for convulsive seizure decrease. Clinically meaningful benefits across multiple secondary endpoints were observed. No new safety concerns emerged. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Epilepsia (Series 4) is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=194752808
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      – Type: doi
        Value: 10.1002/epi.70164
    Languages:
      – Code: eng
        Text: English
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        PageCount: 12
        StartPage: 2796
    Subjects:
      – SubjectFull: Anticonvulsants
        Type: general
      – SubjectFull: Treatment effectiveness
        Type: general
      – SubjectFull: Childhood epilepsy
        Type: general
      – SubjectFull: Clinical trials
        Type: general
      – SubjectFull: Young adults
        Type: general
      – SubjectFull: Safety
        Type: general
      – SubjectFull: Seizures (Medicine)
        Type: general
    Titles:
      – TitleFull: Soticlestat as an adjunctive therapy in children and young adults with Dravet syndrome.
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              Text: Jun2026
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              Y: 2026
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