UCB, a global biopharmaceutical company, has announced promising results from the GEMZ phase 3 study, revealing that fenfluramine significantly reduces countable motor seizure frequency in individuals with CDKL5 Deficiency Disorder (CDD). The findings were presented at the American Epilepsy Society (AES) meeting held in Atlanta, USA, from December 5 to 9, 2025.
The phase 3 study achieved its primary endpoint, demonstrating a statistically significant reduction in countable motor seizure frequency (CMSF) compared to a placebo. In addition, secondary endpoints indicated clinically meaningful improvements in the Clinical Global Impression–Improvement (CGI-I) scale for patients treated with fenfluramine. The treatment was generally well tolerated, with no new safety signals reported.
UCB plans to seek regulatory approval for fenfluramine to treat seizures associated with CDD as soon as possible. This marks the third developmental and epileptic encephalopathy for which fenfluramine will be submitted for regulatory consideration.
Study Overview and Results
The GEMZ phase 3 study was a randomized, double-blind, placebo-controlled trial involving 86 participants aged 1 to 35 years diagnosed with CDD and experiencing uncontrolled seizures. Results indicated that patients receiving fenfluramine (n=42), with a dosage of 0.7 mg/kg/day (up to a maximum of 26 mg/day), experienced a median reduction of 47.6% in CMSF from baseline. In contrast, the placebo group (n=44) exhibited only a 2.8% reduction.
The estimated median reduction between treatment groups during a 14-week titration and maintenance period was recorded at 52.7% (95% CI: −70.0 to −36.7). Notably, 45.2% of fenfluramine-treated patients achieved at least a 50% reduction in CMSF, compared to just 4.5% of those on placebo.
Patients receiving fenfluramine also reported an increase in countable motor seizure-free days, with a median of over six additional seizure-free days per month compared to the placebo group. Assessments revealed that 38.1% of fenfluramine patients were rated as ‘much improved’ or ‘very much improved’ on the CGI-I scale, contrasting sharply with 6.8% of the placebo group.
Significance and Future Steps
Fiona du Monceau, Executive Vice President of Patient Evidence at UCB, emphasized the importance of these results, stating, “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 affected by this ultra-rare disorder, which includes frequent, treatment-resistant seizures.
UCB is currently conducting a long-term, open-label extension study to further evaluate fenfluramine’s safety and tolerability over a 54-week period, which includes a 52-week treatment phase and a 2-week taper. CDD, an ultra-rare developmental and epileptic encephalopathy, is characterized by multiple drug-resistant seizures and severe global neurodevelopmental delays. The disorder affects approximately 1 in 40,000 to 60,000 live births, with a median onset of six weeks.
Currently, fenfluramine is approved in the European Union, United States, and Japan for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome. However, it has yet to receive approval for use in CDD by any regulatory authority globally.
The full press release detailing the study and its implications is available on UCB’s website. For further inquiries, UCB’s communications team is available for contact.
