Survey identifies Fever-Related Seizure Reduction as Key Feature of CDKL5 Deficiency Disorder

A national, cross-sectional survey (NCT06663163) of patients with CDKL5 Deficiency Disorder (CDD) in China revealed that fever-related reductions in seizure frequency is a distinctive and possibly unique clinical feature of the disorder. Study authors noted that these findings could provide evidence that informs the development of therapeutic strategies and support further fundamental research for patients with CDD.¹

Presented at the 2025 American Epilepsy Society (AES) Annual Meeting, held December 5-9, in Atlanta, Georgia, the survey aimed to clarify the association between fever and seizure frequency for therapeutic implications by investigating the genotype-phenotype correlation in a cohort of CDD patients. A total of 102 eligible patients from various regions of China were enrolled between March 2024 and November 2024, but 18 were eventually excluded due to missing data. The primary outcome for the remaining 84 patients was the change in seizure frequency during and after fevers, compared with baseline recorded 1 month prior to the fever.

Results from the survey, led by Siyi Wang, a PhD student at Capital Medical University in Beijing, China, showed that more than half of patients (55.95%; n = 47) experienced a significant decrease in seizure frequency during high fever, and nearly one-third of patients (32.14%; n = 27) who had daily seizure achieved at least 1 seizure-free day. Notably, seizure reduction persisted for 1 to 40 days after fever in 20 patients (23.81%). Notably, the reduction in seizures during fever occurred in all patients, regardless of their clinical characteristics or symptoms, type, or location, of CDD.

CDD is a rare, X-linked neurodevelopmental disorder caused by pathogenic variants in the CDKL5 gene. The disorder is characterized by early-onset and often refractory seizures, typically beginning in the first months of life, alongside severe developmental delays, hypotonia, and impaired motor and cognitive function. Patients may also present cortical visual impairment, sleep disturbances, and gastrointestinal issues. While seizure type and severity vary, CDD is increasingly recognized as a distinct clinical entity with a consistent genotype–phenotype relationship, making early genetic diagnosis critical for guiding management and emerging therapeutic interventions.

READ MORE: Fenfluramine Meets End Points in Phase 3 GEMZ Study of CDKL5 Deficiency Disorder

Earlier this year, a notable double-blind, placebo-controlled, fixed-dose, phase 3 study tested the safety and efficacy of fenfluramine (Fintepla), an FDA-approved therapy for Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), in patients with CDD. Results indicated the antiseizure medication met its primary and secondary end points by demonstrating statistically significant changes relative to placebo of percent change in countable motor seizure frequency and a favorable safety profile.²

Otherwise known as GEMZ, the trial included 87 children and adults aged 1-35 with a CDD diagnosis and uncontrolled seizures. Overall, fenfluramine maintained a consistent safety profile that was similar to previous observations in DS and LGS, in addition to meeting primary and secondary end points. Funded by UCB, the company remains committed to an open-label, flexible-dose, long-term, 52-week extension phase of the study to further test the therapy’s long-term safety and tolerability in CDD.

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REFERENCES
1. Wang S, Du J, Liu J, et al. Nationwide Survey of Association Between Fever and Epileptic Seizure in CDKL5 Deficiency Disorder Revealed Therapeutic Implications. Presented at: 2025 American Epilepsy Society (AES) Annual Meeting; December 5-9; Atlanta, Georgia.
2. UCB announces positive results from GEMZ phase 3 study of fenfluramine in CDKL5 Deficiency Disorder. News release. UCB. June 27, 2025. Accessed June 27, 2025. https://www.ucb.com/newsroom/press-releases/article/ucb-announces-positive-results-from-gemz-phase-3-study-of-fenfluramine-in-cdkl5-deficiency-disorder