UCB announced positive results from its Phase 3 GEMZ study investigating adjunctive fenfluramine in CDKL5 deficiency disorder (CDD), marking a significant milestone for patients with this ultra-rare developmental and epileptic encephalopathy. The randomized, double-blind, placebo-controlled study met its primary endpoint and most key secondary endpoints in 87 children and adults aged 1-35 years with CDD and uncontrolled seizures.
Study Design and Primary Endpoint
The Phase 3 study examined the efficacy, safety, and pharmacokinetics of adjunctive fenfluramine treatment in a fixed-dose, multi-center design. The primary endpoint was based on the median percent change in countable motor seizure frequency (CMSF) between baseline and the titration plus maintenance phase, comparing fenfluramine with the placebo group. Full results will be presented at an upcoming scientific congress.
"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)," said Fiona du Monceau, Executive Vice President, Patient Evidence, UCB. "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."
Understanding CDKL5 Deficiency Disorder
CDKL5 deficiency disorder is an ultra-rare DEE characterized by refractory infantile-onset epilepsy and severe global neurodevelopmental delays. The condition results in intellectual, motor, cortical visual, and sleep impairments as major features. CDD is caused by pathogenic variants in the Cyclin Dependent Kinase-like 5 (CDKL5) gene located on the X chromosome.
The disorder affects approximately 1 in 40,000 to 60,000 live births, with a median age of onset of six weeks. This represents a significant unmet medical need, as CDD patients have limited treatment options for managing their seizures and associated symptoms.
Safety Profile and Extension Study
In the Phase 3 study, fenfluramine was generally well-tolerated, with a safety profile consistent with previous studies in Dravet syndrome and Lennox-Gastaut syndrome. UCB is currently conducting an open-label, flexible-dose, long-term 52-week extension phase of the study to characterize the long-term safety and tolerability of fenfluramine in pediatric and adult individuals with CDD.
Third Positive DEE Indication
This positive result represents the third developmental and epileptic encephalopathy population for which fenfluramine has demonstrated positive Phase 3 results. In the European Union, fenfluramine is already approved for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome as an add-on therapy to other anti-epileptic medicines for patients 2 years of age and older. In the United States, fenfluramine oral solution is indicated for the same conditions in patients 2 years of age and older.
Regulatory Path Forward
UCB plans to submit for regulatory approval to bring this potential treatment option to people living with CDD as soon as possible. Currently, fenfluramine is not approved for use in CDD by any regulatory authority worldwide, making this development particularly significant for the patient community.
The company's continued investment in scientific innovation for DEEs underscores the potential impact of expanding fenfluramine's therapeutic applications to address rare neurological conditions with high unmet medical needs. The positive Phase 3 results provide hope for families and patients affected by this devastating ultra-rare disorder.
