UCB presents positive results from GEMZ phase 3 study at AES showing fenfluramine significantly reduces countable motor seizure frequency in CDKL5 Deficiency Disorder

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08 Dec, 2025, 12:02 IST

Seizure reduction: phase 3 study achieved primary endpoint as fenfluramine demonstrated a statistically significant reduction in countable motor seizure frequency (CMSF) compared with placebo¹
Holistic benefit: secondary endpoints showed significant and clinically meaningful improvements in Clinical Global Impression–Improvement (CGI-I) in patients treated with fenfluramine compared with placebo¹
Fenfluramine was generally well tolerated, with no new safety signals identified¹
UCB plans to submit for regulatory approval of fenfluramine for the treatment of seizures associated with CDKL5 Deficiency Disorder (CDD) as soon as possible, marking fenfluramine's third developmental and epileptic encephalopathy (DEE) to be submitted for regulatory approval

BRUSSELS, Dec. 8, 2025 /PRNewswire/ -- UCB, a global biopharmaceutical company, today presented positive efficacy and safety results from the GEMZ phase 3 study investigating adjunctive fenfluramine in children and adults with CDKL5 Deficiency Disorder (CDD) at the American Epilepsy Society (AES) meeting, Atlanta, USA, December 5-9, 2025.¹ The trial met its primary endpoint and key secondary endpoints, demonstrating a statistically significant reduction in countable motor seizure frequency (CMSF) and a clinically meaningful improvement on the Clinical Global Impression–Improvement (CGI-I) scale, compared with placebo.¹

To view the Multimedia News Release, please click:
https://www.multivu.com/ucb/9369551-en-presents-positive-results-from-gemz-phase-3-study-at-aes

"UCB is proud to share these important results with the medical community at AES, especially given the significant unmet need in CDD. Families affected by this ultra-rare condition face immense daily challenges with frequent, treatment-resistant seizures that are profoundly disruptive to daily life. These trial results emphasize the impact that seizure control can have on the lives of patients and their families, and we look forward to working with health authorities to make this treatment available as soon as possible", said Fiona du Monceau, Executive Vice President, Patient Evidence, UCB.

The GEMZ phase 3 study is a randomized, double-blind, placebo-controlled, fixed-dose, multi-center study examining the efficacy, safety, and pharmacokinetics of adjunctive fenfluramine treatment in 86 children and adults aged 1 – 35 years, with a CDD diagnosis and uncontrolled seizures.¹

Phase 3 study results

Patients treated with fenfluramine (n=42) (0.7 mg/kg/day, maximum 26 mg/day) experienced a median reduction of 47.6% in CMSF from baseline, compared with 2.8% for placebo (n=44) (p<0.001).¹ This translated into an estimated median reduction of 52.7% (95% CI: −70.0 to −36.7) between treatment groups during a 14-week titration and maintenance period¹
After 14 weeks, 45.2% (n=19) of fenfluramine-treated patients achieved at least 50% reduction in CMSF, compared with only 4.5% (n=2) of patients who received placebo (p<0.001)¹
Most fenfluramine-treated patients experienced an increase in countable motor seizure-free days, with a median of >6 additional seizure-free days a month from baseline compared with placebo¹
Investigators rated 38.1% (n=16) of patients on fenfluramine as 'much improved' or 'very much improved' on the CGI-I scale, compared with 6.8% (n=3) of those on placebo (p<0.001)¹
According to caregiver's report of improvement, a CGI-I rating of 'much improved' or 'very much improved' was provided by 53.7% (n=22) vs just 2.3% (n=1) in the placebo group (p<0.001)¹

Fenfluramine was generally well tolerated in the trial, with no new safety signals identified and no cases of valvular heart disease (VHD) or pulmonary arterial hypertension (PAH) occurring.¹ Treatment-emergent adverse events (TEAEs) were consistent with the known safety profile of fenfluramine in Dravet syndrome and Lennox-Gastaut syndrome, with 14.3% (n=6) of patients who received fenfluramine experiencing serious TEAEs* compared to 6.7% (n=3) of patients who received placebo.¹ UCB is currently conducting an open-label, flexible-dose, long-term 54-week extension (52-week OLE treatment period + 2-week taper) phase of the study to characterize the long-term safety profile and tolerability of fenfluramine in children and adult individuals with CDD.²

CDD is an ultra-rare, DEE characterized by multiple types of drug-resistant seizures, plus severe global neurodevelopmental delays resulting in intellectual, motor, cortical visual, gastrointestinal and sleep impairments as major features. It is caused by pathogenic variants in the Cyclin Dependent Kinase-like 5 (CDKL5) gene located on the X chromosome and affects four times more females than males. It is estimated that CDD affects approximately 1 in 40,000 to 60,000 live births, with a median age of onset of six weeks.^3,4,5,6,7

In the European Union (EU), fenfluramine is 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.⁸ In the United States, fenfluramine oral solution is indicated for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome in patients 2 years of age and older.⁹ In Japan, fenfluramine is approved for treating seizures associated with Dravet syndrome and Lennox-Gastaut syndrome as an add-on therapy to other anti-epileptic medicines for patients 2 years and older.¹⁰ It is not approved for use in CDD by any regulatory authority worldwide.

*Serious TEAEs included urinary tract infection (n=2), metapneumovirus infection (n=1), RSV pneumonia (n=1), decreased appetite (n=1), and dyskinesia (n=1) in patients on FFA, and gastroenteritis and pneumoperitoneum in the 2 patients on PBO.

The full press release, including notes to editors and important safety information, is available at: https://www.ucb.com/newsroom/press-releases/article/ucb-presents-positive-results-from-gemz-phase-3-study-at-aes-showing-fenfluramine-significantly-reduces-countable-motor-seizure-frequency-in-cdkl5-deficiency-disorder

For further information, contact UCB:

Global Communications
Anna Clark
T: +44.73.8.668.67.79
[email protected]

Corporate Communications, Media Relations
Laurent Schots
T: +32.2.559.92.64
[email protected]

Investor Relations
Antje Witte
T: +32.2.559.94.14
[email protected]

Sahar Yazdian
T: +32.2.559.91.37
[email protected]

References

^[1]Specchio N, Marsh E, Devinsky O, et al. Fenfluramine in CDKL5 deficiency disorder: primary efficacy and safety results from a phase 3, randomized, double-blind, placebo-controlled study. AES. 2025. Abstract number: 2.429.
^[2] ClinicalTrials.gov. NCT05064878. Available at: https://clinicaltrials.gov/study/NCT05064878. Accessed: September 2025.
^[3] Zuberi SM, et al. ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: Position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022;63(6):1349-97.
^[4] Epilepsy Foundation. CDKL5 Deficiency Disorder. Available at: https://www.epilepsy.com/sites/default/files/2023-03/CDKL5_Deficiency_Disorder_March2023.pdf. Accessed: October 2025.
^[5]Rodak M, et al. CDKL5 Deficiency Disorder (CDD)—Rare Presentation in Male. Children (Basel). 2022;9(12):1806.
^[6] Jakimiec M, et al. CDKL5 Deficiency Disorder—A Complex Epileptic Encephalopathy. Brain Sci. 2020;10(2):107.
^[7]Hong W, et al. CDKL5 Deficiency Disorder-Related Epilepsy: A Review of Current and Emerging Treatment. CNS Drugs. 2022;36(6):591–604.
^[8]Fintepla® EU SmPC. https://www.ema.europa.eu/en/documents/product-information/fintepla-epar-product-information_en.pdf. Accessed: September 2025.
^[9] Fintepla® US PI. https://www.ucb-usa.com/fintepla-prescribing-information.pdf. Accessed: September 2025.
^[10] Fintepla^® Japan PI. Available at: フィンテプラ内用液2.2mg/mL (pmda.go.jp). Last accessed: September 2025.