• 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 Improvement: two of the three key secondary endpoints showed significantly greater number of patients demonstrated ≥50% reduction in CMSF from baseline and clinically meaningful improvements in Clinical Global Impression–Improvement (CGI-I) in patients treated with fenfluramine compared with placebo¹
• UCB plans to submit for regulatory approval of fenfluramine for the treatment of seizures associated with CDKL5 deficiency disorder (CDD) as soon as possible, which will mark fenfluramine's third developmental and epileptic encephalopathy (DEE) to be submitted for regulatory approval

ATLANTA, 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 (FFA) in children and adults with CDKL5 deficiency disorder (CDD) at the American Epilepsy Society (AES) meeting in Atlanta, December 5-9, 2025.¹ The trial met its primary endpoint and two of the three key secondary endpoints, demonstrating a statistically significant reduction in countable motor seizure frequency (CMSF), a significant number of patients demonstrating ≥50% reduction in CMSF and clinically meaningful improvement on the Clinical Global Impression-Improvement (CGI-I) scale (as rated by investigator) in patients treated with fenfluramine compared to placebo over 14 weeks.¹

"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. We look forward to working with health authorities to hopefully 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 and safety of adjunctive fenfluramine treatment in 87 children and adults, aged 1 – 35 years, with a confirmed or likely pathogenic CDKL5 mutation, a clinical CDD diagnosis, and uncontrolled seizures.^1,2

Phase 3 study results

• Patients treated with fenfluramine (n=42) (0.7mg/kg/day, maximum 26 mg/day) experienced a median reduction of 47.6% in CMSF from baseline, compared with a 2.8% reduction for placebo (n=44) (p<0.001).¹ This translated into an estimated median difference of -52.7% (95% CI: -70.0 to -36.7) between treatment groups during a 14-week titration and maintenance period.¹
• 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
• Investigators rated 38.1% (n=42) of patients on fenfluramine as "much improved" or "very much improved" on the CGI-I, compared with 6.8% (n=42) of those on placebo (p<0.001) at end of 14 weeks.¹
• According to caregiver's report of improvement, a CGI-I rating of "much improved" or "very much improved" was provided by 52.4% (n=40) of patients on fenfluramine vs 2.3% (n=44) in the placebo group (p<0.001) at end of 14 weeks.¹
• Fenfluramine-treated patients experienced an increase in countable motor seizure-free days; median change from baseline in monthly frequency was 6.4 days in the fenfluramine group compared with 0.1 day in the placebo group.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 Most common TEAEs (reported in ≥10% of patients in either treatment group) were pyrexia, diarrhea, somnolence, decreased appetite and nasopharyngitis. No new safety signals were identified and no cases of valvular heart disease (VHD) or pulmonary arterial hypertension (PAH) occurred in the trial.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 efficacy, safety, 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 seizure onset of six weeks.^3,4,5,6,7,8

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 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, pneumoperitoneum, and hypoxia in the 3 patients on placebo.

For further information, contact UCB: 

US Communications
Becky Malone
T +1.919.605.9600
Email becky.malone@ucb.com

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).

UCB Forward Looking Statement
This document contains forward-looking statements, including, without limitation, statements containing the words "potential", "believes", "anticipates", "expects", "intends", "plans", "seeks", "estimates", "may", "will", "continue" and similar expressions. These forward-looking statements are based on current plans, estimates and beliefs of management. All statements, other than statements of historical facts, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial information, expected legal, arbitration, political, regulatory or clinical results or practices and other such estimates and results. By their nature, such forward-looking statements are not guaranteeing future performance and are subject to known and unknown risks, uncertainties, and assumptions which might cause the actual results, financial condition, performance or achievements of UCB, or industry results, to be materially different from any future results, performance, or achievements expressed or implied by such forward-looking statements contained in this document.

Important factors that could result in such differences include but are not limited to: global spread and impacts of wars, pandemics and terrorism, the general geopolitical environment, climate change, changes in general economic, business and competitive conditions, the inability to obtain necessary regulatory approvals or to obtain them on acceptable terms or within expected timing, costs associated with research and development, changes in the prospects for products in the pipeline or under development by UCB, effects of future judicial decisions or governmental investigations, safety, quality, data integrity or manufacturing issues, supply chain disruption and business continuity risks; potential or actual data security and data privacy breaches, or disruptions of UCB's information technology systems, product liability claims, challenges to patent protection for products or product candidates, competition from other products including biosimilars or disruptive technologies/business models, changes in laws or regulations, exchange rate fluctuations, changes or uncertainties in laws and/or rules pertaining to tax and duties or the administration of such laws and/or rules, and hiring, retention and compliance of employees. There is no guarantee that new product candidates will be discovered or identified in the pipeline, or that new indications for existing products will be developed and approved. Movement from concept to commercial product is uncertain; preclinical results do not guarantee safety and efficacy of product candidates in humans. So far, the complexity of the human body cannot be reproduced in computer models, cell culture systems or animal models. The length of the timing to complete clinical trials and to get regulatory approval for product marketing has varied in the past and UCB expects similar unpredictability going forward. Products or potential products which are the subject of partnerships, joint ventures or licensing collaborations may be subject to disputes between the partners or may prove to be not as safe, effective or commercially successful as UCB may have believed at the start of such partnership. UCB's efforts to acquire other products or companies and to integrate the operations of such acquired companies may not be as successful as UCB may have believed at the moment of acquisition. Also, UCB or others could discover safety, side effects or manufacturing problems with its products and/or devices after they are marketed. The discovery of significant problems with a product similar to one of UCB's products that implicate an entire class of products may have a material adverse effect on sales of the entire class of affected products. Moreover, sales may be impacted by international and domestic trends toward managed care and health care cost containment, including pricing pressure, political and public scrutiny, customer and prescriber patterns or practices, and the reimbursement policies imposed by third-party payers as well as legislation affecting biopharmaceutical pricing and reimbursement activities and outcomes. Finally, a breakdown, cyberattack or information security breach could compromise the confidentiality, integrity and availability of UCB's data and systems.

Given these uncertainties, the public is cautioned not to place any undue reliance on such forward-looking statements. These forward-looking statements are made only as of the date of this document, and do not reflect any potential impacts from the evolving event or risk as mentioned above as well as any other adversity, unless indicated otherwise. The company continues to follow the development diligently to assess the financial significance of these events, as the case may be, to UCB.

UCB expressly disclaims any obligation to update any forward-looking statements in this document, either to confirm the actual results or to report or reflect any change in its forward-looking statements with regard thereto or any change in events, conditions or circumstances on which any such statement is based, unless such statement is required pursuant to applicable laws and regulations.

Indication and Important Safety Information about FINTEPLA^® (fenfluramine) in the US

INDICATIONS AND USAGE
FINTEPLA is indicated for the treatment of seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) in patients 2 years of age and older.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: VALVULAR HEART DISEASE and PULMONARY ARTERIAL HYPERTENSION

• FINTEPLA can cause valvular heart disease and pulmonary arterial hypertension.
• Echocardiogram assessments are required before, during, and after treatment with FINTEPLA.
• FINTEPLA is available only through a restricted program called the FINTEPLA REMS.

CONTRAINDICATIONS
FINTEPLA is contraindicated in patients with hypersensitivity to fenfluramine or any of the excipients in FINTEPLA and with concomitant use, or within 14 days of the administration, of monoamine oxidase inhibitors because of an increased risk of serotonin syndrome.

WARNINGS AND PRECAUTIONS
Valvular Heart Disease and Pulmonary Arterial Hypertension (see Boxed Warning): FINTEPLA can cause valvular heart disease (VHD) and pulmonary arterial hypertension (PAH). Although no patients receiving FINTEPLA developed VHD or PAH in clinical trials for DS and LGS of up to 3 years in duration, cases of VHD and PAH have been reported during use of FINTEPLA in the postmarketing setting. Because of this risk, cardiac monitoring is required prior to starting treatment, during treatment, and after treatment with FINTEPLA concludes. Cardiac monitoring via echocardiogram can identify evidence of VHD and PAH prior to a patient becoming symptomatic, aiding in early detection of these conditions.

Monitoring: Prior to starting treatment, patients must undergo an echocardiogram to evaluate for VHD and PAH. Echocardiograms should be repeated every 6 months, and once 3-6 months post treatment with FINTEPLA.

The prescriber must consider the benefits versus the risks of initiating or continuing treatment with FINTEPLA if any of the following signs are observed via echocardiogram: valvular abnormality or new abnormality; VHD indicated by mild or greater aortic regurgitation or moderate or greater mitral regurgitation, with additional characteristics of VHD (e.g., valve thickening or restrictive valve motion); PAH indicated by elevated right heart/pulmonary artery pressure (PASP >35 mm Hg).

FINTEPLA REMS (see Boxed Warning): FINTEPLA is available only through a restricted distribution program called the FINTEPLA Risk Evaluation and Mitigation Strategy (REMS). Prescribers must be certified by enrolling in the FINTEPLA REMS. Prescribers must counsel patients receiving FINTEPLA about the risk of VHD and PAH, how to recognize signs and symptoms of VHD and PAH, the need for baseline (pretreatment) and periodic cardiac monitoring via echocardiogram during FINTEPLA treatment, and cardiac monitoring after FINTEPLA treatment.

Decreased Appetite and Decreased Weight: FINTEPLA can cause decreases in appetite and weight. Decreases in weight appear to be dose related. Weight should be monitored regularly during treatment with FINTEPLA, and dose modifications should be considered if a decrease in weight is observed.

Somnolence, Sedation, and Lethargy: FINTEPLA can cause somnolence, sedation, and lethargy. Other central nervous system depressants, including alcohol, could potentiate these effects of FINTEPLA. Prescribers should monitor patients for somnolence and sedation and should advise patients not to drive or operate machinery until they have gained sufficient experience on FINTEPLA to gauge whether it adversely affects their ability to drive or operate machinery.

Suicidal Behavior and Ideation: Antiepileptic drugs (AEDs), including FINTEPLA, increase the risk of suicidal thoughts or behaviors in patients taking these drugs for any indication. Patients treated with an AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behaviors, or any unusual changes in mood or behavior.

Withdrawal of Antiepileptic Drugs: As with most AEDs, FINTEPLA should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus. If withdrawal is needed because of a serious adverse reaction, rapid discontinuation can be considered.

Serotonin Syndrome: Serotonin syndrome, a potentially life-threatening condition, may occur with FINTEPLA, particularly during concomitant administration of FINTEPLA with other serotonergic drugs, including, but not limited to, selective serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), bupropion, triptans, dietary supplements (e.g., St. John's Wort, tryptophan), drugs that impair metabolism of serotonin (including monoamine oxidase inhibitors [MAOIs], which are contraindicated with FINTEPLA), dextromethorphan, lithium, tramadol, and antipsychotics with serotonergic agonist activity. Patients should be monitored for the emergence of signs and symptoms of serotonin syndrome, which include mental status changes, autonomic instability, neuromuscular signs, and/or gastrointestinal symptoms. If serotonin syndrome is suspected, treatment with FINTEPLA should be stopped immediately and symptomatic treatment should be started.

Increase in Blood Pressure: FINTEPLA can cause an increase in blood pressure. Rare cases of significant elevation in blood pressure, including hypertensive crisis, have been reported in adult patients treated with fenfluramine, including patients without a history of hypertension. In clinical trials for DS and LGS of up to 3 years in duration, no pediatric or adult patient receiving FINTEPLA developed hypertensive crisis. Monitor blood pressure in patients treated with FINTEPLA.

Glaucoma: Fenfluramine can cause mydriasis and can precipitate angle closure glaucoma. Consider discontinuing treatment with FINTEPLA in patients with acute decreases in visual acuity or ocular pain.

ADVERSE REACTIONS
The most common adverse reactions observed in DS studies (incidence at least 10% and greater than placebo) were decreased appetite; somnolence, sedation, lethargy; diarrhea; constipation; abnormal echocardiogram; fatigue, malaise, asthenia; ataxia, balance disorder, gait disturbance; blood pressure increased; drooling, salivary hypersecretion; pyrexia; upper respiratory tract infection; vomiting; decreased weight; fall; status epilepticus.

The most common adverse reactions observed in the LGS study (incidence at least 10% and greater than placebo) were diarrhea; decreased appetite; fatigue; somnolence; vomiting.

To report SUSPECTED ADVERSE REACTIONS, contact UCB, Inc. at 1-844-599-2273 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information, including Boxed Warning and Medication Guide, for additional Important Safety Information on FINTEPLA.

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: TBC.
² ClinicalTrials.gov. NCT05064878. Available at: https://clinicaltrials.gov/study/NCT05064878. Accessed: November 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/node/2447996#What-Is-CDKL5-Deficiency-Disorder-(CDD)?. Accessed: November 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 Leonard H, et al. CDKL5 deficiency disorder: clinical features, diagnosis, and management. Lancet Neurol. 2022 June ; 21(6): 563–576. doi:10.1016/S1474-4422(22)00035-7
⁹ FINTEPLA (fenfluramine) oral solution: U.S. prescribing information. Smyrna, GA: UCB, Inc.

FINTEPLA^® is a registered trademark of the UCB Group of Companies.
©2025 UCB, Inc., Smyrna, GA 30080. All rights reserved.
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