UCB, a global biopharmaceutical company, announced significant findings from its GEMZ phase 3 study, revealing that fenfluramine substantially reduces the frequency of countable motor seizures in patients with CDKL5 Deficiency Disorder (CDD). The results were presented at the American Epilepsy Society (AES) meeting held in Atlanta, USA, from December 5 to December 9, 2025.
The trial successfully met its primary endpoint, demonstrating a statistically significant reduction in countable motor seizure frequency (CMSF) when compared to a placebo. In addition to the primary outcome, key secondary endpoints indicated substantial and clinically meaningful improvements in the Clinical Global Impression–Improvement (CGI-I) scale for patients receiving fenfluramine.
According to Fiona du Monceau, Executive Vice President for Patient Evidence at UCB, “UCB is proud to share these important results with the medical community at AES, especially given the significant unmet need in CDD.” She highlighted the daily challenges faced by families coping with CDD, a condition characterized by frequent, treatment-resistant seizures that severely disrupt daily life. The results underline the potential impact that effective seizure control could have on patients and their families.
The GEMZ phase 3 study was designed as a randomized, double-blind, placebo-controlled trial involving 86 children and adults aged 1 to 35 years diagnosed with CDD and experiencing uncontrolled seizures. Participants treated with fenfluramine showed a median reduction of 47.6% in CMSF from baseline, compared to just 2.8% for those on placebo, with a statistically significant p-value of p<0.001.
In terms of patient improvement, the study reported that 38.1% of patients treated with fenfluramine were rated as ‘much improved’ or ‘very much improved’ on the CGI-I scale, contrasting with only 6.8% of the placebo group. Caregiver reports indicated that 53.7% of patients receiving fenfluramine experienced substantial improvements, compared to a mere 2.3% in the placebo cohort.
Safety assessments revealed that fenfluramine was generally well tolerated among participants, with no new safety signals identified. Notably, there were no reported cases of valvular heart disease or pulmonary arterial hypertension during the trial. Treatment-emergent adverse events, which were consistent with the known safety profile of fenfluramine in other conditions such as Dravet syndrome, were observed in 14.3% of patients receiving fenfluramine, compared to 6.7% for those on placebo.
UCB is also conducting a long-term extension phase of the study, which includes a flexible-dose regimen over 54 weeks, to further evaluate the safety and tolerability of fenfluramine in individuals with CDD.
CDKL5 Deficiency Disorder is an ultra-rare genetic condition resulting in multiple types of drug-resistant seizures and severe neurodevelopmental delays. It is caused by mutations in the Cyclin Dependent Kinase-like 5 (CDKL5) gene on the X chromosome and predominantly affects females, with an estimated prevalence of 1 in 40,000 to 60,000 live births.
Currently, fenfluramine is approved in the European Union, the United States, and Japan for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome, but it has yet to receive regulatory approval for use in CDD. UCB plans to submit for regulatory approval of fenfluramine for CDD treatment as soon as possible, marking it as the third developmental and epileptic encephalopathy (DEE) to seek such approval.
This study underscores the promise of fenfluramine as a potential treatment option for patients suffering from this complex condition, offering hope to families facing the challenges of managing CDD. For further details, UCB has made additional resources available through their press release.
