UCB, a global biopharmaceutical company, revealed promising results from its GEMZ phase 3 study of fenfluramine for treating seizures associated 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 study achieved its primary endpoint, showing a statistically significant reduction in countable motor seizure frequency (CMSF) when compared to a placebo.
The trial included 86 participants aged between 1 and 35 years, all diagnosed with CDD and experiencing uncontrolled seizures. Patients treated with fenfluramine (42 participants) experienced a median reduction of 47.6% in CMSF from their baseline, while those on placebo (44 participants) showed only a 2.8% reduction. These results underscore the potential of fenfluramine as a significant treatment option for patients grappling with this challenging condition.
In addition to meeting primary endpoints, secondary endpoints presented a clinically meaningful improvement on the Clinical Global Impression–Improvement (CGI-I) scale for those on fenfluramine. Notably, 38.1% of patients rated as ‘much improved’ or ‘very much improved’ compared to just 6.8% from the placebo group. According to caregiver reports, 53.7% of those on fenfluramine also indicated substantial improvement.
Fiona du Monceau, Executive Vice President of Patient Evidence at UCB, emphasized the importance of these results, stating, “Families affected by this ultra-rare condition face immense daily challenges with frequent, treatment-resistant seizures that are profoundly disruptive to daily life.” She expressed UCB’s commitment to collaborating with health authorities to expedite the availability of this treatment.
The GEMZ phase 3 study was designed as a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of fenfluramine. The treatment was generally well-tolerated, with no new safety signals identified. Serious treatment-emergent adverse events (TEAEs) occurred in 14.3% of those treated with fenfluramine compared to 6.7% in the placebo group. Importantly, no cases of valvular heart disease or pulmonary arterial hypertension were reported.
UCB is currently conducting a long-term extension phase of the study to further evaluate the safety profile of fenfluramine. CDD is a rare developmental and epileptic encephalopathy characterized by multiple types of drug-resistant seizures, alongside severe neurodevelopmental delays. This condition is linked to mutations in the Cyclin Dependent Kinase-like 5 (CDKL5) gene, predominantly affecting females.
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 not yet received regulatory approval for use in CDD.
UCB plans to submit applications for regulatory approval of fenfluramine for CDD treatment as soon as possible, marking an important step forward in addressing the needs of patients with this debilitating disorder. The study’s results highlight the potential for fenfluramine to significantly enhance the quality of life for individuals living with CDD and their families.
