Neuropediatrics 2021; 52(S 01): S1-S53
DOI: 10.1055/s-0041-1739606
Poster Abstracts

Fenfluramine Treatment Improves Everyday Executive Functioning in Patients with Lennox-Gastaut Syndrome: Analysis from a Phase 3 Clinical Trial

K. I. Bishop
1   Global Pharma Consultancy, LLC, Muncy, Pennsylvania, United States
,
P. K. Isquith
2   Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
G. A. Gioia
3   Children's National Health System, Rockville, Maryland, United States
,
K. G. Knupp
4   Children's Hospital Colorado, Aurora, Colorado, United States
,
I. E. Scheffer
5   University of Melbourne, Austin Hospital and Royal Children's Hospital, Melbourne, Victoria, Australia
,
J. Sullivan
6   University of California San Francisco, Benioff Children's Hospital, San Francisco, California, United States
,
R. Nabbout
7   Hôpital Universitaire Necker - Enfants Malades, Paris, France
,
G. Farfel
8   Zogenix GmbH, Germany
,
B. S. Galer
8   Zogenix GmbH, Germany
,
S. Shore
8   Zogenix GmbH, Germany
,
J. Grünert
8   Zogenix GmbH, Germany
,
A. R. Gammaitoni
9   Zogenix, Inc., Emeryville, California, United States
› Author Affiliations
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Background/Purpose: Fenfluramine reduced frequencies of drop seizures and generalized tonic-clonic seizures in a recent Lennox-Gastaut syndrome (LGS) RCT. Purpose was to determine whether fenfluramine improves everyday executive function in a randomized clinical trial (RCT) of LGS patients.

Methods: LGS patients received placebo or fenfluramine (0.2 or 0.7 mg/kg/day) for 14 weeks. Executive function was evaluated at baseline and at week 14 for patients aged 5 to 18 years with the Behavior Rating Inventory of Executive Function (BRIEF) parent form; items were mapped to the updated BRIEF2. Clinically meaningful worsening in BRIEF2 indexes (Behavior Regulation [BRI], Emotion Regulation [ERI], Cognitive Regulation [CRI], Global Executive Composite [GEC]) from baseline to week 14 was defined exceeding a Reliable Change Index (RCI) ≥80% certainty. Clinically meaningful improvement was defined using a RCI ≥95% certainty. Active versus placebo treatment groups were compared statistically (Somers’ D).

Results: Data were analyzed for 137 patients (placebo, n = 45; fenfluramine, n = 92). Median T-scores at baseline were in the clinically elevated range (T ≥ 65) for BRI, CRI, and GEC (T = 66, 65, and 67, respectively; range: 35–90). Fenfluramine was associated with no significant worsening in any of the BRIEF2 indexes compared to placebo (p > 0.05; RCI ≥ 80%). Fenfluramine was associated with significant and clinically meaningful improvements in CRI (27 vs. 13%, p = 0.046) and GEC (25 vs. 11%; p = 0.034) versus placebo (RCI > 95%).

Conclusion: In an LGS population with a high frequency of executive function impairment at baseline, parents of approximately 25% of children treated with fenfluramine for 14 weeks observed clinically meaningful improvement in CRI and GEC.

The data were first presented at AAN 2021 Virtual Annual Meeting.



Publication History

Article published online:
28 October 2021

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