UCB Unveils Positive Findings from GEMZ Phase 3 Study on Fenfluramine for Seizures

UCB, a leading global biopharmaceutical company, showcased the encouraging outcomes from the GEMZ Phase 3 study at the recent American Epilepsy Society (AES) meeting held in Atlanta from December 5 to 9, 2025. This study focused on the use of fenfluramine as an adjunctive treatment for individuals diagnosed with CDKL5 Deficiency Disorder (CDD), a condition characterized by various types of drug-resistant seizures and severe developmental delays.

Significant Seizure Reduction

The trial successfully hit its primary endpoint, reporting a statistically significant decrease in countable motor seizure frequency (CMSF) among participants receiving fenfluramine compared to those on a placebo. Specifically, patients treated with fenfluramine (group size: 42) displayed a median CMSF reduction of 47.6%, in stark contrast to just 2.8% in the placebo group (group size: 44) (p<0.001). This was equivalent to a remarkable median overall reduction of 52.7% between the two groups during a 14-week titration and maintenance period.

Moreover, 45.2% of participants treated with fenfluramine experienced at least a 50% reduction in seizure frequency, whereas only 4.5% of the placebo group achieved this level of improvement. The trial further revealed that most fenfluramine-treated patients enjoyed an increase in seizure-free days, averaging more than six extra days a month.

Improvements in Quality of Life

Beyond the reduction in seizure frequency, the study also illustrated significant enhancements in overall well-being as indicated by the Clinical Global Impression–Improvement (CGI-I) scale. Investigators rated 38.1% of fenfluramine group patients as 'much improved' or 'very much improved', while only 6.8% of the placebo group received similar feedback (p<0.001). Caregivers echoed these sentiments, with 53.7% of them noting significant improvement compared to just 2.3% in those receiving a placebo.

Favorable Safety Profile

Fenfluramine exhibited a favorable tolerance profile during the study, with no new safety signals emerging. Notably, there were no reported cases of valvular heart disease or pulmonary arterial hypertension associated with the treatment. The serious treatment-emergent adverse events (TEAEs) noted among fenfluramine participants included urinary tract infections and respiratory infections, consistent with previous reports of fenfluramine's safety in treating other epilepsy syndromes like Dravet and Lennox-Gastaut syndromes.

UCB is optimizing its efforts to pursue regulatory approval for fenfluramine in treating seizures linked to CDD, viewing this as a critical step towards addressing the significant unmet needs of families affected by this rare disorder. The company aims to make this potentially life-changing therapy available as soon as possible.

Understanding CDKL5 Deficiency Disorder

CDKL5 Deficiency Disorder is a rare epileptic encephalopathy resulting from mutations in the CDKL5 gene located on the X chromosome. It predominantly affects females and leads to various debilitating symptoms, including severe intellectual disabilities and multiple forms of drug-resistant seizures. The condition impacts approximately 1 in every 40,000 to 60,000 live births, highlighting the urgent need for effective treatments.

The successful results from this GEMZ Phase 3 study reinforce UCB’s commitment to advancing solutions for challenging neurologic conditions and reflects their dedication to improving the lives of patients and their families.

For further information on UCB's research and developments, visit UCB's official website.