In a significant advancement for epilepsy treatment, UCB, a global biopharmaceutical company, announced that its Phase 3 clinical trial of fenfluramine for CDKL5 deficiency disorder (CDD) met its primary and key secondary endpoints. This development offers new hope for patients and families affected by this rare and challenging condition.
Understanding CDKL5 Deficiency Disorder
CDKL5 deficiency disorder is a rare genetic condition caused by mutations in the CDKL5 gene, which is crucial for normal brain development and function. The disorder is characterized by early-onset, treatment-resistant seizures, as well as severe developmental delays, intellectual disabilities, and motor impairments. Symptoms typically appear within the first few months of life, and the condition affects approximately 1 in 40,000 to 60,000 live births, with a higher prevalence in females.
The Phase 3 Clinical Trial
The Phase 3 study conducted by UCB was a randomized, double-blind, placebo-controlled, fixed-dose, multi-center trial. It involved 87 participants aged 1 to 35 years who had a confirmed diagnosis of CDD and experienced uncontrolled seizures. Participants were randomly assigned to receive either adjunctive fenfluramine or a placebo, in addition to their existing antiseizure medications.
The primary endpoint of the study was the median percent change in countable motor seizure frequency from baseline to the combined titration and maintenance phases. Fenfluramine demonstrated a significant reduction in seizure frequency compared to the placebo group, meeting the primary endpoint. Additionally, the trial met most key secondary endpoints, further supporting the efficacy of fenfluramine in this patient population.
Fenfluramine was generally well tolerated among study participants. The safety profile observed in the trial was consistent with previous studies of fenfluramine in other epileptic conditions, such as Dravet syndrome and Lennox-Gastaut syndrome. No new safety concerns were identified, and the incidence of adverse events was comparable between the fenfluramine and placebo groups.
Implications for Patients and Families
The positive results from this Phase 3 trial represent a significant milestone in the treatment of CDD. Currently, treatment options for CDD are limited, and many patients continue to experience frequent, debilitating seizures despite multiple medications. The demonstrated efficacy and safety of fenfluramine offer a potential new therapeutic option for managing seizures in individuals with CDD.
Fiona du Monceau, Executive Vice President of Patient Evidence at UCB, stated, “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.”
Next Steps
Following the successful completion of the Phase 3 trial, UCB plans to submit regulatory applications to health authorities worldwide to seek approval for the use of fenfluramine in treating seizures associated with CDD. The company is also conducting an open-label, flexible-dose, long-term extension study to further evaluate the long-term safety and tolerability of fenfluramine in this patient population.
The full results of the Phase 3 trial are expected to be presented at upcoming scientific meetings, providing the medical community with more detailed insights into the study’s findings.
