Fenfluramine in CDKL5 Deficiency Disorder

Posted on 16 July, 2025 - Epilepsy, Industry News

UCB announces positive results from GEMZ phase 3 study

  • Phase 3 study met primary and key secondary clinical endpoints, marking the third developmental and epileptic encephalopathies (DEE) population to experience positive outcomes from treatment with fenfluramine
  • Results underscore the impact of UCB’s continued investment in scientific innovation to advance new treatments for DEEs
  • CDKL5 Deficiency Disorder (CDD) is an ultra-rare, severe DEE with onset in early infancy, a high unmet medical need, and limited treatment options
  • UCB plans to submit for regulatory approval to bring this potential treatment option to people living with CDD as soon as possible 

27 June 2025: UCB has announced that the phase 3 study investigating the safety and efficacy of adjunctive fenfluramine in CDKL5 Deficiency Disorder (CDD) met its primary and key secondary endpoints.1 The study is a randomised, double-blind, placebo-controlled, fixed-dose, multi-centre study examining the efficacy, safety, and pharmacokinetics of adjunctive fenfluramine treatment in 87 children and adults aged 1 – 35, with a CDD diagnosis and uncontrolled seizures.2

“These results pave the way for creating significant therapeutic progress and represent an important milestone in UCB’s mission to bring meaningful innovation to individuals and families affected by developmental and epileptic encephalopathies (DEEs). We are grateful to the patients, families, and researchers who made this progress possible, and we look forward to working with the health authorities to make treatment available as soon as possible”, said Fiona du Monceau, Executive Vice President, Patient Evidence, UCB.

CDD is an ultra-rare DEE with refractory infantile-onset epilepsy and severe global neurodevelopmental delays resulting in intellectual, motor, cortical visual, and sleep impairments as major features.3 It is caused by pathogenic variants in the Cyclin Dependent Kinase-like 5 (CDKL5) gene located on the X chromosome. It is estimated that CDD affects approximately 1 in 40,000 to 60,000 live births, with a median age of onset of six weeks.3,4

The primary endpoint of the study is based on the median percent change in countable motor seizure frequency (CMSF) between baseline and the titration plus maintenance phase, comparing fenfluramine with the placebo group.2 Full results will be presented at an upcoming scientific congress.

In the study, fenfluramine was generally well-tolerated, and the safety profile was consistent with previous studies on DS/LGS.1 UCB is currently conducting an open-label, flexible-dose, long-term 52-week extension phase of the study to characterise the long-term safety and tolerability of fenfluramine in pediatric and adult individuals with CDD.2

In the European Union (EU), fenfluramine is approved for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome as an add-on therapy to other anti-epileptic medicines for patients 2 years of age and older.5 In the United States, fenfluramine oral solution is indicated for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome in patients 2 years of age and older.6 It is not approved for use in CDD by any regulatory authority worldwide.

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References: 

  1. UCB data on file. 2025
  2. ClinicalTrials.gov. NCT05064878. Available at: https://clinicaltrials.gov/study/NCT05064878. Accessed: June 2025.
  3. Overview of Medical-scientific Research in the Netherlands (OMON). A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Fixed-Dose, Multicenter Study to Examine the Efficacy and Safety of ZX008 in Subjects with CDKL5 Deficiency Disorder Followed by an Open-Label Extension. 2022. Available at: https://onderzoekmetmensen.nl/en/node/56446/pdf. Accessed: June 2025.
  4. Zuberi et al. ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: Position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia.2022;63(6):1349-97.
  5. Fintepla® EU SmPC. https://www.ema.europa.eu/en/documents/product-information/fintepla-epar-product-information_en.pdf. Accessed June 2025.
  6. Fintepla® US PI. https://www.ucb-usa.com/fintepla-prescribing-information.pdf. Accessed June 2025.