Key takeaways
Rare disease trial design requires careful structuring: The GEMZ trial’s two-part, multi-phase design highlights the complexity of running rigorous studies in low-prevalence populations like CDKL5 Deficiency Disorder.
Durable outcomes support long-term follow-up planning: Positive, long-term efficacy and safety data from open-label extensions underscore the value of extended monitoring to support future regulatory decisions.
Global coordination is essential for DEE trials: The multi-center approach across age groups and geographies demonstrates the need for operational excellence in recruiting and managing highly specific patient cohorts.
UCB has announced positive results from the Phase III GEMZ clinical trial (NCT05064878) of adjunctive fenfluramine in participants with CDKL5 Deficiency Disorder (CDD). Data show that fenfluramine met its primary endpoint along with other key secondary endpoints.1
In a press release, Fiona du Monceau, executive vice president, patient evidence, UCB, said: "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). 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.”
Clinical trial design: A closer look at GEMZ methodology
- The GEMZ trial is a randomized, double-blind, placebo-controlled, fixed-dose, multi-center study investigating the efficacy, safety, and pharmacokinetics of adjunctive fenfluramine.
- The study participants consisted of 87 children and adults aged 1-35 with a CDD diagnosis and uncontrolled seizures.
- GEMZ’s primary endpoint is based on the median percent change in countable motor seizure frequency between baseline and the titration plus maintenance phase.
- This trial is a two-part study. Part one, highlighted in this announcement, has a duration of 20 weeks and consists of four stages: baseline period, titration period, maintenance period, and a two-week transition period.2
- Part two is a 54-week, long-term extension study consisting of a 52-week treatment period followed by a taper period.
Long-term efficacy in Dravet syndrome supports continued development
Earlier in May 2024, UCB shared final data from a three-year open-label extension (OLE) study of fenfluramine in Dravet syndrome at the International Child Neurology Congress (ICNC). Results from the OLE study were positive, with fenfluramine treatment for up to three years being generally well tolerated.3
- As of January 2023, 375 patients were enrolled in the OLE.
- No new or unexpected safety signals were identified.
- Patients experienced clinically significant, durable reductions in monthly convulsive seizure frequency.
- 61.4% of caregivers and 62.5% of investigators reported global functioning scores as “much improved” or “very much improved.”
- In participants under 6 years of age, clinically meaningful improvement was reported by 69% of caregivers and 66.7% of investigators.
In a press release from the time, Elaine C. Wirrell, MD, principal investigator, said: “The final analyses from the OLE studies being presented at this year’s ICNC meeting reinforce the long-term treatment potential and efficacy of fenfluramine for up to three years, showing profound, durable reductions in median monthly convulsive seizure frequency in people living with Dravet syndrome. The ultimate goals are reducing seizure frequency for the patient and maximizing developmental potential and quality of life.”
Regulatory milestones for fenfluramine in pediatric epilepsies
Fenfluramine was approved by the FDA as Fintepla for the treatment of seizures associated with Lennox-Gastaut syndrome in patients two years of age and older in March 2022. The approval was based on positive results from a Phase III study of 263 patients, in which Fintepla significantly reduced the frequency of drop seizures compared to placebo.4
In a press release from the time, Mike Davis, then head of global epilepsy, UCB, said: “The approval of fenfluramine for Lennox-Gastaut syndrome highlights our continued commitment to bringing differentiated medicines to patients who may not be well controlled on current therapies, and their caregivers. We are proud to add fenfluramine as a treatment for Dravet syndrome, and now Lennox-Gastaut syndrome, to our portfolio of epilepsy medicines to help reduce the impact and burden of seizures, including severe epilepsy syndromes that have high pediatric morbidity and mortality rates.”
References
1. UCB announces positive results from GEMZ phase 3 study of fenfluramine in CDKL5 Deficiency Disorder. News release. UCB. June 27, 2025. Accessed June 30, 2025. https://www.ucb.com/newsroom/press-releases/article/ucb-announces-positive-results-from-gemz-phase-3-study-of-fenfluramine-in-cdkl5-deficiency-disorder
2. A Study to Investigate the Efficacy and Safety of ZX008 in Subjects With CDKL5 Deficiency Disorder. ClinicalTrials.gov. Updated June 27, 2025. Accessed June 30, 2025. https://clinicaltrials.gov/study/NCT05064878
3. UCB presents final open-label extension FINTEPLA®▼(fenfluramine)[1] data at International Child Neurology Congress (ICNC) Annual Meeting. News release. UCB. May 8, 2024. Accessed June 30, 2025. https://www.ucb.com/newsroom/press-releases/article/ucb-presents-final-open-label-extension-finteplarvfenfluramine1-data-at-international-child-neurology-congress-icnc-annual-meeting
4. U.S. FDA Approves FINTEPLA[®] ▼(fenfluramine) Oral Solution for Treatment of Seizures Associated with Lennox-Gastaut Syndrome (LGS). News release. UCB. March 28, 2022. Accessed June 30, 2025. https://www.ucb.com/newsroom/press-releases/article/us-fda-approves-finteplar-vfenfluramine-oral-solution-for-treatment-of-seizures-associated-with-lennox-gastaut-syndrome-lgs
