Brian Moseley, MD, Senior Medical Director at UCB, discusses the GEMZ clinical trial of fenfluramine in patients with CDKL5 deficiency disorder (CDD).
CDD is a rare genetic disorder characterized by difficult‑to‑control seizures and severe neuro‑developmental impairment. It’s caused by a mutation of the cyclin-dependent kinase-like 5 (CDKL5) gene, located on the X chromosome.
At the American Association of Neurology 2026 meeting, primary results were presented from the GEMZ (NCT05064878) clinical trial of fenfluramine in patients with CDD. GEMZ is a phase 3 randomized, double-blind, placebo-controlled, fixed-dose, multicenter study evaluating the safety and efficacy of fenfluramine. Fenfluramine is a phenethylamine that is structurally similar to serotonin that has been proven to be effective in treating pharmacoresistant seizures.
Patients were randomized to fenfluramine 0.7 mg/kg/day or placebo over 14 weeks (including a two week titration period [T] and a 12 week maintenance period [M]). The primary endpoint was countable motor seizure frequency (CMSF) percentage change from baseline over T+M versus placebo.
Safety and modified intent-to-treat populations included 87 and 86 patients, respectively. Most patients received 3 or more concomitant anti-seizure medications. Baseline median CMSF was 44 for patients on fenfluramine and 49 for patients on placebo.
Significant differences in efficacy endpoints were observed with fenfluramine versus placebo. Median percentage CMSF change was −47.6% for fenfluramine versus −2.8% for placebo. A total 45.2% of fenfluramine-treated patients achieved 50% or greater CMSF, compared to 4.5% of placebo patients. Additionally, 38.1% on fenfluramine versus 6.8% on placebo demonstrated clinically meaningful improvement on Clinical Global Impression–Improvement scale. Median percentage change in generalized tonic-clonic seizure frequency from baseline was −61.5% for fenfluramine (n=14) and −13.5% for placebo (n=18).
Four patients discontinued due to treatment-emergent adverse events. Of patients on fenfluramine, the most common adverse events were pyrexia, diarrhea, and somnolence. No new safety signals identified and no valvular heart disease or pulmonary arterial hypertension cases observed.
To learn more about CDD and other rare neurological conditions, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/
