UCB has reported positive findings from the Gemz phase 3 study evaluating adjunctive fenfluramine in children and adults living with CDKL5 deficiency disorder (CDD), with data showing a significant reduction in countable motor seizure frequency compared with placebo. The results were presented at the American Epilepsy Society (AES) meeting.

CDD is an ultra-rare developmental and epileptic encephalopathy defined by multiple drug-resistant seizure types alongside severe neurodevelopmental impairment. Most individuals experience seizure onset within the first months of life, and currently no approved treatment specifically targets CDD-related seizures.

The double-blind, placebo-controlled Gemz study enrolled 86 people aged 1–35 years with confirmed CDD and treatment-resistant seizures. Participants received either fenfluramine or placebo over a 14-week titration and maintenance period. According to UCB, patients receiving fenfluramine achieved a median reduction of 47.6% in seizure frequency from baseline, compared with 2.8% in the placebo group.

After 14 weeks, 45.2% of patients treated with fenfluramine reached a 50% or greater reduction in countable motor seizures, while only 4.5% in the placebo group achieved a similar response. Investigators also reported more seizure-free days in the fenfluramine cohort, with a median gain of more than six additional days per month compared with placebo.

Secondary measures supported these findings. Investigators rated 38.1% of fenfluramine-treated patients as ‘much improved’ or ‘very much improved’ on the Clinical Global Impression–Improvement scale, compared with 6.8% on placebo. Caregivers reported even greater perceived benefit, with more than half rating patients on fenfluramine as ‘much improved’ or ‘very much improved’.

Fiona du Monceau, executive vice president for patient evidence at UCB, said: “These trial results emphasize the impact that seizure control can have on the lives of patients and their families.”

Fenfluramine was generally well tolerated and no new safety signals were identified. No cases of valvular heart disease or pulmonary arterial hypertension occurred in the study. Reported adverse events were consistent with the medicine’s known profile in Dravet syndrome and Lennox-Gastaut syndrome. UCB continues to run a long-term open-label extension to gather additional safety and tolerability data.

Fenfluramine is already approved in Europe, the US and Japan for seizures associated with Dravet syndrome and Lennox-Gastaut syndrome but is not authorised for CDD in any region. UCB said it plans to submit fenfluramine for regulatory review in CDD as soon as possible, marking the company’s third developmental and epileptic encephalopathy programme to move into the approval process.

If authorised, fenfluramine would become the first targeted treatment for seizures linked to CDD, addressing a substantial unmet need in this population.