UCB Reveals Promising Phase 3 Study Results for Fenfluramine in CDKL5 Deficiency Disorder at AES 2025

UCB Presents Positive Results from Phase 3 GEMZ Study

UCB, a prominent biopharmaceutical company, announced significant findings from their GEMZ phase 3 study concerning fenfluramine, which was presented during the American Epilepsy Society (AES) meeting held in Atlanta from December 5-9, 2025. The study focused on the effects of fenfluramine in individuals suffering from CDKL5 Deficiency Disorder (CDD), a rare and serious neurological condition.

The trial successfully met its primary objective, showcasing a statistically significant reduction in countable motor seizure frequency (CMSF) for patients receiving fenfluramine as compared to those on a placebo. Specifically, results indicated an impressive 47.6% reduction in CMSF in the fenfluramine group against a mere 2.8% reduction in the placebo group (p<0.001). This marked success highlights fenfluramine's potential effectiveness as an adjunctive treatment for CDD, especially given the challenges families face in managing frequent, treatment-resistant seizures.

Moreover, the study extended beyond primary endpoints, evidencing notable secondary benefits assessed through the Clinical Global Impression–Improvement (CGI-I) scale. Here, 38.1% of fenfluramine-treated patients were rated as 'much improved' or 'very much improved,' contrasting sharply with just 6.8% in the placebo group (p<0.001). These findings underline fenfluramine’s therapeutic promise, signaling a beacon of hope for those battling CDD.

Fiona du Monceau, UCB's Executive Vice President of Patient Evidence, expressed gratitude for the opportunity to share these pivotal results at the AES meeting, emphasizing the urgent unmet needs of families affected by CDD. Du Monceau highlighted how the struggle with frequent seizures heavily disrupts daily life for patients, and affirmed UCB's commitment to expedite the regulatory approval process for fenfluramine to improve accessibility for those in need.

The GEMZ study was a rigorous randomized, double-blind, placebo-controlled trial involving 86 pediatric and adult participants aged between 1 to 35 who were diagnosed with CDD and had uncontrolled seizures. This methodical design aimed to determine not just the efficacy of fenfluramine but also its safety profile.

As part of the findings, fenfluramine was generally well tolerated. No new safety signals emerged during the trial, nor were there instances of valvular heart disease or pulmonary arterial hypertension noted among participants. The profile of treatment-emergent adverse events (TEAEs) mirrored that seen in fenfluramine's prior studies involving other syndromes, such as Dravet syndrome and Lennox-Gastaut syndrome, reinforcing its established safety narrative.

The study results are encouraging not only for the present but for future avenues of treatment. Following this promising phase 3 study, UCB has plans to submit for fenfluramine's regulatory approval for treating seizures in CDD, marking it as the third developmental form of epileptic encephalopathy (DEE) linked to fenfluramine that UCB will seek approval for.

CDKL5 Deficiency Disorder is characterized by its ultra-rare nature, with estimates suggesting it affects 1 in 40,000 to 60,000 live births, predominantly impacting females, often causing severe neurodevelopmental delays and multiple seizure types resistant to standard treatments. The cyclic nature of CDKL5 mutations leads to various challenges, emphasizing the necessity for effective therapeutic options.

Currently, fenfluramine enjoys regulatory approval in the European Union, Japan, and the United States for epilepsy types like Dravet syndrome and Lennox-Gastaut syndrome, yet it awaits similar approval for use in CDD worldwide.

In summary, UCB's announcements at the AES meeting shine a light on an innovative approach to tackling the significant difficulties presented by CDKL5 Deficiency Disorder. As the company moves forward with their regulatory processes, the results herald a potential shift in treatment paradigms for patients and families navigating the complexities of this condition.