UCB announces positive results from GEMZ phase 3 study of fenfluramine in CDKL5 Deficiency Disorder

Brussels, Belgium – 27th June 2025 – 07:00 CET – UCB, a global biopharmaceutical company, today announced that the phase 3 study investigating the safety and efficacy of adjunctive fenfluramine in CDKL5 Deficiency Disorder (CDD) met its primary and key secondary endpoints.¹ The study is a randomized, double-blind, placebo-controlled, fixed-dose, multi-center study examining the efficacy, safety, and pharmacokinetics of adjunctive fenfluramine treatment in 87 children and adults aged 1 – 35, with a CDD diagnosis and uncontrolled seizures.²

"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”, said Fiona du Monceau, Executive Vice President, Patient Evidence, UCB.

CDD is an ultra-rare DEE with refractory infantile-onset epilepsy and severe global neurodevelopmental delays resulting in intellectual, motor, cortical visual, and sleep impairments as major features.³ It is caused by pathogenic variants in the Cyclin Dependent Kinase-like 5 (CDKL5) gene located on the X chromosome. 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

The primary endpoint of the study is based on the median percent change in countable motor seizure frequency (CMSF) between baseline and the titration plus maintenance phase, comparing fenfluramine with the placebo group.² Full results will be presented at an upcoming scientific congress.

In the study, fenfluramine was generally well-tolerated, and the safety profile was consistent with previous studies on DS/LGS.¹ UCB is currently conducting an open-label, flexible-dose, long-term 52-week extension phase of the study to characterize the long-term safety and tolerability of fenfluramine in pediatric and adult individuals with CDD.²

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.⁵ 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.⁶ It is not approved for use in CDD by any regulatory authority worldwide.

For further information, contact UCB: 

Global Communications
Anna Clark
T: +44.73.8.668.67.79
Anna.clark@ucb.comm 

Corporate Communications, Media Relations
Laurent Schots 
T +32.2.559.92.64 
Laurent.schots@ucb.com 

Investor Relations
Antje Witte         
T +32.2.559.94.14
antje.witte@ucb.com    

Sahar Yazdian
T +32.2.559.91.37
sahar.yazdian@ucb.com

About UCB
UCB, Brussels, Belgium (www.ucb.com) is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With approximately 9 000 people in approximately 40 countries, the company generated revenue of € 6.15 billion in 2024. UCB is listed on Euronext Brussels (symbol: UCB).  

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Important Safety Information about FINTEPLA^®▼ (fenfluramine) in the EU¹

Indications: 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.

Dosage and Administration: Please refer to SmPC for full information. Should be initiated and supervised by physicians with experience in the treatment of epilepsy. Fintepla is prescribed and dispensed according to the Fintepla controlled access programme. Dravet syndrome: Patients who are not taking stiripentol: Starting dose is 0.1 mg/kg twice daily (0.2 mg/kg/day). After 7 days, if tolerated, can increase dose to 0.2 mg/kg twice daily (0.4 mg/kg/day). After an additional 7 days, if tolerated and further seizure reduction required, can increase dose to a maximum of 0.35 mg/kg twice daily (0.7 mg/kg/day), which is the recommended maintenance dose. Patients requiring more rapid titration may increase the dose every 4 days. Do not exceed maximum daily dose of 26 mg (13 mg twice daily). Patients who are taking stiripentol: Starting dose is 0.1 mg/kg twice daily (0.2 mg/kg/day). After 7 days, if tolerated, can increase dose to 0.2 mg/kg twice daily (0.4 mg/kg/day), which is the recommended maintenance dose. Patients requiring more rapid titration may increase the dose every 4 days. Do not exceed a total dose of 17 mg (8.6 mg twice daily). Lennox-Gastaut syndrome: Starting dose is 0.1 mg/kg twice daily (0.2 mg/kg/day). After 7 days, the dose should be increased to 0.2 mg/kg twice daily (0.4 mg/kg/day), if tolerated. After an additional 7 days, if tolerated, dose should be increased to 0.35 mg/kg twice daily (0.7 mg/kg/day), which is the recommended maintenance dose. Do not exceed maximum daily dose of 26 mg (13 mg twice daily). Discontinuation: When discontinuing treatment, decrease the dose gradually. As with all anti-epileptic medicines, avoid abrupt discontinuation when possible to minimize the risk of increased seizure frequency and status epilepticus. A final echocardiogram should be conducted 3-6 months after the last dose of treatment with fenfluramine. Renal impairment: Generally, no dose adjustment is recommended when administered to patients with mild to severe renal impairment, however, a slower titration may be considered. If adverse reactions are reported, a dose reduction may be needed. Has not been studied in patients with end-stage renal disease. Not known if fenfluramine or its active metabolite, norfenfluramine, is dialyzable. Hepatic impairment: Hepatic impairment: Generally, no dose adjustment is recommended when Fintepla is administered without concomitant stiripentol to patients with mild and moderate hepatic impairment (Child-Pugh Class A and B). In patients with severe hepatic impairment (Child-Pugh C) not receiving concomitant stiripentol, the maximum dosage is 0.2mg/kg twice daily, and the maximal total daily dose is 17 mg. There are limited clinical data on the use of Fintepla with stiripentol in patients with mild impaired hepatic function. A slower titration may be considered in patients with hepatic impairment and a dose reduction may be needed if adverse reactions are reported. No clinical data is available on the use of Fintepla with stiripentol in moderate and severe hepatic impairment, therefore not recommended for use. Elderly: No data available. Paediatric population: Safety and efficacy in children below 2 years of age not yet established. No data available. Contraindications: Hypersensitivity to active substance or any excipients. Aortic or mitral valvular heart disease and pulmonary arterial hypertension. Within 14 days of the administration of monoamine oxidase inhibitors due to an increased risk of serotonin syndrome. Warnings and Precautions: Aortic or mitral valvular heart disease and pulmonary arterial hypertension: Prior to starting treatment, patients must undergo an echocardiogram to establish a baseline and exclude any pre-existing valvular heart disease or pulmonary hypertension. Conduct echocardiogram monitoring every 6 months for the first 2 years and annually thereafter. If an echocardiogram indicates pathological valvular changes, consider follow-up earlier to evaluate whether the abnormality is persistent. If pathological abnormalities seen on echocardiogram, evaluate the benefit versus risk of continuing fenfluramine treatment with the prescriber, caregiver and cardiologist. Once treatment is discontinued for any reasons, a final echocardiogram should be conducted 3-6 months after the last dose of treatment with fenfluramine. If echocardiogram findings suggestive of pulmonary arterial hypertension, perform a repeat echocardiogram as soon as possible and within 3 months to confirm these findings. If echocardiogram finding is confirmed suggestive of an increased probability of pulmonary arterial hypertension defined as intermediate probability, conduct a benefit-risk evaluation of continuation of Fintepla by the prescriber, carer and cardiologist. If echocardiogram suggests a high probability, it is recommended fenfluramine treatment should be stopped. Decreased appetite and weight loss: Fenfluramine can cause decreased appetite and weight loss - an additive effect can occur in combination with other anti-epileptic medicines such as stiripentol. Monitor the patient’s weight. Undertake risk-benefit evaluation before starting treatment if history of anorexia nervosa or bulimia nervosa. Fintepla controlled access programme: A controlled access programme has been created to 1) prevent off-label use in weight management in obese patients and 2) confirm that prescribing physicians have been informed of the need for periodic cardiac monitoring in patients taking Fintepla. Somnolence: Fenfluramine can cause somnolence which could be potentiated by other central nervous system depressants. Suicidal behaviour and ideation: Suicidal behaviour and ideation have been reported in patients treated with anti-epileptic medicines in several indications. Advise patients and caregivers to seek medical advice should any signs of suicidal behaviour and ideation emerge. Serotonin syndrome: Serotonin syndrome, a potentially life-threatening condition, may occur with fenfluramine treatment, particularly with concomitant use of other serotonergic agents; with agents that impair metabolism of serotonin such as MAOIs; or with antipsychotics that may affect the serotonergic neurotransmitter systems. Carefully observe the patient, particularly during treatment initiation and dose increases. Increased seizure frequency: A clinically relevant increase in seizure frequency may occur during treatment, which may require adjustment in the dose of fenfluramine and/or concomitant anti-epileptic medicines, or discontinuation of fenfluramine, should the benefit-risk be negative. Cyproheptadine: Cyproheptadine is a potent serotonin receptor antagonist and may therefore decrease the efficacy of fenfluramine. If cyproheptadine is added to treatment with fenfluramine, monitor patient for worsening of seizures. If fenfluramine treatment is initiated in a patient taking cyproheptadine, fenfluramine’s
efficacy may be reduced. Glaucoma: Fenfluramine can cause mydriasis and can precipitate angle closure glaucoma. Discontinue therapy in patients with acute decreases in visual acuity. Consider discontinuation if ocular pain of unknown origin. Effect of CYP1A2 or CYP2B6 inducers: Co-administration with strong CYP1A2 inducers or CYP2B6 inducers will decrease fenfluramine plasma concentrations, which may lower the efficacy of fenfluramine. If co-administration is considered necessary, the patient should be monitored for reduced efficacy and a dose increase of fenfluramine could be considered provided that it does not exceed twice the
maximum daily dose (52 mg/day). If a strong CYP1A2 or CYP2B6 inducer is discontinued during maintenance treatment with fenfluramine, consider gradual reduction of the fenfluramine dosage to the dose administered prior to initiating the inducer. Effect of CYP1A2 or CYP2D6 inhibitors: Initiation of concomitant treatment with a strong CYP1A2 or CYP2D6 inhibitor may result in higher exposure and, therefore, adverse events should be monitored, and a dose reduction may be needed in some patients. Excipients: Contains sodium ethyl para-hydroxybenzoate (E 215) and sodium methyl para-hydroxybenzoate (E 219) - may cause allergic reactions
(possibly delayed). It also contains sulfur dioxide (E 220) which may rarely cause severe hypersensitivity reactions and bronchospasm. Patients with rare glucose-galactose malabsorption should not take this medicine. The product contains less than 1 mmol sodium (23 mg) per the maximum daily dose of 12 mL; essentially ‘sodium-free’. Contains glucose - may be harmful to teeth. Interactions: Pharmacodynamic interactions with other CNS depressants increase the risk of aggravated central nervous system depression. An
increase in dose may be necessary when coadministered with rifampicin or a strong CYP1A2 or CYP2B6 inducer. In in vitro studies coadministration with a strong CYP1A2 or CYP2D6 inhibitor may result in higher exposure (see section 4.4 of the SmPC). Coadministration with CYP2D6 substrates or MATE1 substrates may increase their plasma concentrations. Co-administration with CYP2B6 or CYP3A4 substrates may decrease their plasma concentrations. Pregnancy and lactation: Limited data in pregnant women. As a precaution, avoid use of Fintepla in pregnancy. It is unknown whether fenfluramine/metabolites are excreted in human milk. Animal
data have shown excretion of fenfluramine/metabolites in milk. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Fintepla taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Drive and use machines.: Fintepla has moderate influence on the ability to drive/ use machines as it may cause somnolence and fatigue. Advise patients not to drive or operate machinery until they have sufficient experience to gauge whether it adversely
affects their abilities. Adverse effects: Dravet syndrome: Very common (≥1/10): Upper respiratory tract infection, decreased appetite, somnolence, diarrhoea, pyrexia, fatigue, blood glucose decreased, echocardiogram abnormal (Consisted of trace and mild mitral regurgitation, and trace aortic regurgitation, which are considered physiologic). Common (≥1/100 to <1/10): Bronchitis, abnormal behaviour, aggression, agitation, insomnia, mood swings, ataxia, hypotonia, lethargy, seizure, status epilepticus, tremor, constipation, salivary hypersecretion, weight decreased and blood prolactin increased. Lennox-Gastaut syndrome: Very common (≥1/10): Upper respiratory tract infection, decreased appetite, somnolence, diarrhoea, vomiting, fatigue. Common (≥1/100 to <1/10): Bronchitis, influenza, pneumonia, seizure, status epilepticus, lethargy, tremor, constipation, salivary hypersecretion, blood prolactin increased, weight decreased, fall. Refer to SmPC for other adverse reactions. 

▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

Refer to the European Summary of Product Characteristics for other adverse reactions and full Prescribing Information. 
https://www.ema.europa.eu/en/documents/product-information/fintepla-epar-product-information_en.pdf (accessed October 2024)

References: 

1. UCB data on file. 2025
2. ClinicalTrials.gov. NCT05064878. Available at: https://clinicaltrials.gov/study/NCT05064878. Accessed: June 2025.
3. Overview of Medical-scientific Research in the Netherlands (OMON). A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Fixed-Dose, Multicenter Study to Examine the Efficacy and Safety of ZX008 in Subjects with CDKL5 Deficiency Disorder Followed by an Open-Label Extension. 2022. Available at: https://onderzoekmetmensen.nl/en/node/56446/pdf. Accessed: June 2025.
4. Zuberi 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.
5. Fintepla^® EU SmPC. https://www.ema.europa.eu/en/documents/product-information/fintepla-epar-product-information_en.pdf. Accessed June 2025.
6. Fintepla^® US PI. https://www.ucb-usa.com/fintepla-prescribing-information.pdf. Accessed June 2025.