UCB Announces Promising Phase 3 Results for Fenfluramine in CDKL5 Deficiency Disorder, Marking a Major Step Forward in Rare Epilepsy Treatment
UCB, a global biopharmaceutical company committed to developing innovative therapies for neurological and immunological conditions, has announced positive top-line results from its Phase 3 GEMZ study evaluating fenfluramine as an adjunctive treatment for seizures associated with CDKL5 Deficiency Disorder (CDD). The trial met both its primary and key secondary endpoints, signaling a potential breakthrough in a condition with few, if any, effective treatment options.
The GEMZ study is a randomized, double-blind, placebo-controlled, fixed-dose, multi-center clinical trial designed to assess the safety, efficacy, and pharmacokinetics of fenfluramine in children and adults aged 1 to 35 years diagnosed with CDD who experience uncontrolled seizures. A total of 87 patients participated in the study, highlighting the scale and significance of this effort in the context of an ultra-rare and severely debilitating disorder.
A Milestone for UCB and the CDD Community
Fiona du Monceau, Executive Vice President of Patient Evidence at UCB, emphasized the gravity of this development, stating:
“These results pave the way for creating significant therapeutic progress and represent an important milestone in UCB’s mission to bring meaningful innovation to individuals and families affected by developmental and epileptic encephalopathies (DEEs). We are grateful to the patients, families, and researchers who made this progress possible, and we look forward to working with the health authorities to make treatment available as soon as possible.”
The successful outcome of the GEMZ Phase 3 study underscores UCB’s broader strategy of addressing underserved rare neurological diseases and reinforces its commitment to investing in areas with high unmet medical need. These data offer new hope to the CDD community, which has long struggled with a lack of effective seizure control therapies.
Understanding CDKL5 Deficiency Disorder (CDD)
CDKL5 Deficiency Disorder is a rare, X-linked developmental and epileptic encephalopathy (DEE) caused by mutations in the Cyclin Dependent Kinase-like 5 (CDKL5) gene, located on the X chromosome. The disorder primarily affects females due to the gene’s X-linked nature but can also impact males. It is characterized by early-onset, treatment-resistant seizures, beginning as early as six weeks of age, and profound global neurodevelopmental impairment.
Children and adults with CDD commonly experience a range of neurological and systemic challenges, including intellectual disability, severe motor dysfunction, cortical visual impairment, sleep disturbances, and difficulties in communication. It is estimated that CDD affects approximately 1 in every 40,000 to 60,000 live births, classifying it as an ultra-rare disorder. The lack of approved therapies specifically indicated for CDD means that treatment strategies are often based on off-label use of anti-seizure medications, with limited success.
Key Findings from the GEMZ Phase 3 Study
The primary endpoint of the GEMZ study focused on the median percentage change in countable motor seizure frequency (CMSF) from baseline through the titration and maintenance phases. Patients receiving fenfluramine experienced a statistically significant reduction in CMSF compared to those receiving a placebo, indicating the drug’s ability to reduce the frequency of debilitating seizures in this difficult-to-treat population.
While detailed data have not yet been publicly disclosed, UCB confirmed that the trial achieved its key secondary endpoints as well, further supporting the therapeutic potential of fenfluramine in managing seizures associated with CDD. The full dataset is expected to be presented at an upcoming international scientific conference, which will provide greater clarity on the magnitude of fenfluramine’s clinical benefits.
Favorable Safety and Tolerability Profile
Fenfluramine was generally well-tolerated among participants in the study, with a safety profile consistent with that observed in previous trials involving patients with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS)—two other severe childhood-onset epilepsies for which fenfluramine is already approved in multiple markets. The most common adverse events were mild to moderate in intensity and did not differ significantly from known safety patterns.
Importantly, the study is continuing with an open-label, flexible-dose extension phase lasting 52 weeks. This extension will allow researchers to gather critical long-term data on the safety, tolerability, and durability of fenfluramine’s seizure-reducing effects in both pediatric and adult populations living with CDD.
Regulatory Status and Path Forward
Fenfluramine, originally developed decades ago as an appetite suppressant, has reemerged in recent years as a promising treatment for rare epilepsies. In both the European Union (EU) and the United States, the drug is currently approved as an add-on therapy for seizures associated with Dravet syndrome and Lennox-Gastaut syndrome in patients aged 2 years and older. It is marketed under the brand name Fintepla® and has shown considerable success in significantly reducing seizure frequency while improving quality of life in these populations.
However, fenfluramine is not yet approved by any regulatory agency for the treatment of CDD, and the results of the GEMZ study will be central to UCB’s future regulatory submissions. The company has indicated its intent to engage with global health authorities—including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA)—to expedite review and potential approval for this new indication.
Implications for the Future
The successful Phase 3 trial of fenfluramine in CDD represents a beacon of hope for families, clinicians, and researchers working in the field of rare and developmental epilepsies. Historically, the management of CDD has been fraught with trial-and-error medication regimens, most of which fail to provide adequate seizure control or improve cognitive and motor development. With no approved therapies specifically targeting this condition, the unmet need is profound.
UCB’s latest clinical milestone not only provides a potential treatment option for individuals with CDD but also reinforces the importance of precision medicine and targeted research in ultra-rare disease spaces. If approved, fenfluramine could become the first medication indicated specifically for seizures associated with CDKL5 Deficiency Disorder, opening new doors for therapeutic innovation and patient care.
The company’s continued investment in long-term safety studies and its collaborative engagement with the CDD community demonstrate a model for responsible drug development in complex, underserved conditions.
As UCB prepares to share full trial results with the scientific and medical communities, the broader epilepsy and rare disease fields will be closely watching how these findings reshape the landscape of treatment options for one of the most challenging and poorly understood pediatric epilepsies. For families affected by CDD, the possibility of more effective seizure control and improved daily life may soon be within reach.
