EEC 2026 | The Phase III GEMZ trial of fenfluramine in CDKL5 deficiency disorder
Nicola Specchio, MD, PhD, Bambino Gesù Children’s Hospital, Rome, Italy, discusses the results of a Phase III GEMZ trial (NCT05064878) of fenfluramine in CDKL5 deficiency disorder. Prof. Specchio highlights that the trial met its primary endpoint, with the fenfluramine-treated group achieving a reduction in countable motor seizures compared with placebo, and notes that the treatment was generally well-tolerated with no significant safety signals identified. This interview is part of our virtual coverage of the 16th European Epilepsy Congress (EEC), which took place in Athens, Greece.
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Transcript
CDKL5 deficiency disorder has been widely discussed at the last European Epilepsy Congress in Athens in early September. As you know, CDD is an ultra-rare drug-resistant developmental and epileptic encephalopathy, and in the randomized controlled trial with fenfluramine, patients aged between 1 and 35 years when enrolled, and they should have had the clinical diagnosis of CDD, and also they were carrying the genetic variant of CDKL5...
CDKL5 deficiency disorder has been widely discussed at the last European Epilepsy Congress in Athens in early September. As you know, CDD is an ultra-rare drug-resistant developmental and epileptic encephalopathy, and in the randomized controlled trial with fenfluramine, patients aged between 1 and 35 years when enrolled, and they should have had the clinical diagnosis of CDD, and also they were carrying the genetic variant of CDKL5. All patients received fenfluramine, 0.7 milligrams per kilogram per day or placebo over a two-week titration and then 12 weeks of maintenance period. And as a general result of this RCT, the primary endpoint was definitely met and the fenfluramine group achieved a reduction of 52% median difference in percent reduction in countable motor seizures, comparing the baseline versus the placebo. In terms of adverse events, pyrexia, diarrhea, and somnolence were reported in about 20% of fenfluramine-treated patients and other adverse events were seen less frequently. There were actually overall in the trial no safety signals identified with fenfluramine and no deaths were definitely reported in this RCT. So overall, as a conclusion, I can just tell that the results of this study demonstrate that fenfluramine may be a definitely promising therapy for pediatric and other patients with CDKL5 deficiency disorder.
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Disclosures
NS has served on scientific advisory boards for GW Pharma, BioMarin, Arvelle, Marinus and Takeda; has received speaker honoraria from Eisai, Biomarin, Livanova, Sanofi; has served as an investigator for Zogenix, Marinus, Biomarin, UCB, Roche; the remaining authors have no conflicts of interest.
