21ьз╕ C

Epilepsia Publishes Final Analysis of Open-Label Extension Study of Long-Term Safety and Effectiveness of FINTEPLA® (fenfluramine) in Children and Adults with Dravet Syndrome

News Provided by PR Newswire2025-03-12

Epilepsia Publishes Final Analysis of Open-Label Extension Study of Long-Term Safety and Effectiveness of FINTEPLA® (fenfluramine) in Children and Adults with Dravet Syndrome

[12-March-2025]

FINTEPLA is approved by the U.S. Food and Drug Administration (FDA) for the treatment of seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) in patients two years of age and older¹
Results showed the most common treatment-emergent adverse events were pyrexia, nasopharyngitis and decreased appetite, with no valvular heart disease or pulmonary arterial hypertension observed in this study²
FINTEPLA was associated with a statistically significant and clinically meaningful sustained reduction in monthly convulsive seizure frequency (MCSF)^2,3

ATLANTA, March 12, 2025 /PRNewswire/ -- UCB, a global biopharmaceutical company, today announced that Epilepsia published findings from the final analysis of the long-term open-label extension (OLE) study evaluating the safety and effectiveness of FINTEPLA^® (fenfluramine) in patients with Dravet syndrome (DS). Results showed that FINTEPLA was generally well tolerated. The most common treatment-emergent adverse events (TEAEs) were pyrexia, nasopharyngitis and decreased appetite.² The efficacy analysis showed a statistically significant and clinically meaningful sustained reduction in monthly convulsive seizure frequency (MCSF) with FINTEPLA in both children and adults with DS.²

"Anti-seizure medications that provide long-term tolerability and effectiveness are needed for patients with DS, who often have many other medical conditions that are adversely impacted by seizure frequency and severity," said Ingrid E. Scheffer, MBBS, Ph.D., co-author of the publication and laureate professor, chair of pediatric neurology at the University of Melbourne. "This analysis, showing that FINTEPLA was generally well tolerated over the long-term and increased seizure-free days, builds on previous findings from randomized, controlled trials in adults and children with DS and provides additional evidence of the sustained tolerability and efficacy of this treatment."

The OLE study enrolled patients with DS who had participated in one of three randomized, placebo-controlled Phase 3 trials of FINTEPLA or who were 19 to 35 years old and had not received FINTEPLA prior to study entry. The primary objective of the OLE study was to assess the long-term safety and tolerability of FINTEPLA. Efficacy endpoints evaluated the median percentage change in MCSF from Day 1 to end of study (EOS) and Day 31 to EOS compared with baseline; the proportion of patients to achieve seizure reduction thresholds; the longest convulsive seizure-free interval; and the percentage of convulsive seizure-free days in the modified intent-to-treat (mITT) population. Clinical Global Impression-Improvement (CGI-I) ratings by caregiver and investigator and changes in baseline in the Quality of Life Childhood Epilepsy (QOLCE) score were also evaluated.

Results showed that FINTEPLA was generally well tolerated with only 11 patients (2.9%) discontinuing therapy due to an adverse event. TEAEs occurring in ≥10% of patients were pyrexia, nasopharyngitis, decreased appetite, seizure, decreased blood glucose, diarrhea, abnormal echocardiogram (only physiologic regurgitation), upper respiratory tract infection, influenza, vomiting, and ear infection. No valvular heart disease or pulmonary arterial hypertension was observed in this study.

Efficacy outcomes showed a sustained reduction in MCSF with FINTEPLA in the mITT population of 324 patients, with a median change from Day 1 to EOS compared with baseline of -66.8% (p<0.001) and -67.8% (p<0.001) from Day 31 to EOS compared with baseline. FINTEPLA was effective in both patients less than six years old and those six years or older. The analysis showed that 64.2% of patients experienced a 50% or more reduction in MCSF; two patients were seizure-free throughout the OLE. From Month 1 to EOS, there was a significant 20.3% median increase in convulsive seizure-free days (p<0.0001). Caregivers rated 61.3% of patients as much/very much improved at the last visit on the CGI-I, as did 62.6% of investigators. Significant improvements from baseline were observed in several subscales of the QOLCE, including energy/fatigue, language, general health, QOL and overall QOL.

DS is a rare, severe, drug-resistant developmental and epileptic encephalopathy (DEE) that is characterized by seizure onset before the first year of life and developmental slowing or regression.^4,5 DS is often challenging to diagnose.⁶ Patients often experience multiple seizure types⁵ and effects beyond seizures, including cognitive impairment, speech impairment, sleep and gait issues, and behavioral issues, including impulsivity and hyperactivity, that can adversely impact quality of life.^5-7

"The ability to meaningfully address the complexities of Dravet, inclusive of the severe and often debilitating seizures, is critical for patients living with this rare syndrome and those who care for them," said Brad Chapman, head of U.S. epilepsy and rare syndromes at UCB. "The publication of these new long-term findings, in which patients were exposed to FINTEPLA for up to 3.5 years and experienced durable and clinically meaningful reductions in seizure frequency, emphasizes the benefit of this treatment and our commitment to helping improve outcomes for patients with DS and other rare epilepsies."

About FINTEPLA

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

There is an association between serotonergic drugs with 5-HT2B receptor agonist activity, including fenfluramine (the active ingredient in FINTEPLA), and 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): Because of the association between serotonergic drugs with 5-HT2B receptor agonist activity, including fenfluramine (the active ingredient in FINTEPLA), and valvular heart disease (VHD) and pulmonary arterial hypertension (PAH), cardiac monitoring via echocardiogram is required prior to starting treatment, during treatment, and after treatment with FINTEPLA concludes. Cardiac monitoring via echocardiogram can aid in early detection of these conditions. In clinical trials for DS and LGS of up to 3 years in duration, no patient receiving FINTEPLA developed VHD or PAH.

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 at 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 (eg, valve thickening or restrictive valve motion); PAH indicated by elevated right heart/pulmonary artery pressure (PASP >35 mmHg).

FINTEPLA REMS Program (see Boxed Warning): FINTEPLA is available only through a restricted distribution program called the FINTEPLA Risk Evaluation and Mitigation Strategy (REMS) Program. 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. Patients must enroll in the FINTEPLA REMS and comply with ongoing monitoring requirements. The pharmacy must be certified by enrolling in the FINTEPLA REMS and must only dispense to patients who are authorized to receive FINTEPLA. Wholesalers and distributors must only distribute to certified pharmacies. Further information is available at www.FinteplaREMS.com or by telephone at 1-877-964-3649.

Decreased Appetite and Decreased Weight: FINTEPLA can cause decreases in appetite and weight. Decreases in weight appear to be dose related. Approximately half of the patients with LGS and most patients with DS resumed the expected measured increases in weight during the open-label extension studies. 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 (CNS) 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.

Anyone considering prescribing FINTEPLA or any other AED must balance the risk of suicidal thoughts or behaviors with the risks of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behaviors. Should suicidal thoughts and behaviors emerge during treatment, consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

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 (eg, 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 (eg, agitation, hallucinations, coma), autonomic instability (eg, tachycardia, labile blood pressure, hyperthermia), neuromuscular signs (eg, hyperreflexia, incoordination), and/or gastrointestinal symptoms (eg, nausea, vomiting, diarrhea). 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, has 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.

DRUG INTERACTIONS

Strong CYP1A2, CYP2B6, or CYP3A Inducers: Coadministration with strong CYP1A2, CYP2B6, or CYP3A inducers will decrease fenfluramine plasma concentrations. If coadministration of a strong CYP1A2, CYP2B6, or CYP3A inducer with FINTEPLA is necessary, monitor the patient for reduced efficacy and consider increasing the dosage of FINTEPLA as needed. If a strong CYP1A2, CYP2B6, or CYP3A inducer is discontinued during maintenance treatment with FINTEPLA, consider gradual reduction in the FINTEPLA dosage to the dose administered prior to initiating the inducer.

Strong CYP1A2 or CYP2D6 Inhibitors: Coadministration with strong CYP1A2 or CYP2D6 inhibitors will increase fenfluramine plasma concentrations. If FINTEPLA is coadministered with strong CYP1A2 or CYP2D6 inhibitors, the maximum daily dosage of FINTEPLA is 20 mg. If a strong CYP1A2 or CYP2D6 inhibitor is discontinued during maintenance treatment with FINTEPLA, consider gradual increase in the FINTEPLA dosage to the dose recommended without CYP1A2 or CYP2D6 inhibitors. If FINTEPLA is coadministered with stiripentol and a strong CYP1A2 or CYP2D6 inhibitor, the maximum daily dosage of FINTEPLA is 17 mg.

USE IN SPECIFIC POPULATIONS

In patients with severe impairment of kidney function (estimated glomerular filtration rate [eGFR]) 15 to 29 mL/min/1.73m², dosage adjustments are recommended. FINTEPLA has not been studied in patients with kidney failure (eGFR <15 mL/min/1.73m²).

Combined molar exposures of fenfluramine and norfenfluramine were increased in subjects with various degrees of hepatic impairment (Child-Pugh Class A, B, and C), necessitating a dosage adjustment in these patients.

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.

For further information, contact UCB:

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

US Communications
Becky Malone
T +1.919.605.9600
Email becky.malone@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 €5.3 billion in 2023. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCBUSA.

About Epilepsy
Epilepsy is a common neurological condition worldwide and affects approximately 50 million people. Epilepsy can develop in any person at any age and is usually diagnosed after a person has had at least two seizures (or after one seizure with a high risk for more) that were not caused by some known medical condition.

About UCB in Epilepsy
For three decades we've been committed to people living with epilepsy and their families, surrounding the patient and caregiver through every step of their care journey. At our core we have a responsibility to elevate the healthcare ecosystem. Because of this, we have established our legitimacy on the front lines of epilepsy research, development, and treatment innovation. But our past breakthroughs are only a prologue to our future. We will continue to reimagine how we care for patients, leveraging today's expertise for a better tomorrow. With so much experience behind us and so much potential ahead, we are more invested than ever in profoundly improving the lives of those living with or caring for those with epilepsy or a rare epilepsy syndrome – through our relentless pursuit of a seizure-free life.

Forward looking statements
This press release may contain forward-looking statements including, without limitation, statements containing the words "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 guarantees of 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 differ materially from those that may be expressed or implied by such forward-looking statements contained in this press release. Important factors that could result in such differences include: 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; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, product liability claims, challenges to patent protection for products or product candidates, competition from other products including biosimilars, changes in laws or regulations, exchange rate fluctuations, changes or uncertainties in tax laws or the administration of such laws, and hiring and retention of its employees. There is no guarantee that new product candidates will be discovered or identified in the pipeline, will progress to product approval 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 differences 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, you should not place undue reliance on any of such forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labelling in any market, or at any particular time, nor can there be any guarantee that such products will be or will continue to be commercially successful in the future.

UCB is providing this information, including forward-looking statements, only as of the date of this press release. UCB expressly disclaims any duty to update any information contained in this press release, 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.

Additionally, information contained in this document shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any offer, solicitation or sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such jurisdiction.

References

FINTEPLA (fenfluramine) oral solution: U.S. prescribing information. Smyrna, GA: UCB, Inc.
Scheffer IE, Nabbout R, Lagae L, et al. Long-term safety and effectiveness of fenfluramine in children and adults with Dravet syndrome. Epilepsia. 2025.
Scheffer IE, Nabbout R, Lagae L, et al. Safety and Effectiveness of Adjunctive Fenfluramine in an Open-Label Extension Study of Patients With Dravet Syndrome. [Poster] Presented at: International Child Neurology Conference; 6-10 May 2024; Cape Town, South Africa; 667.
Dravet C. The core Dravet syndrome phenotype. Epilepsia. 2011;52(Suppl. 2):3-9.
Nabbout R, Hyland K, Loftus R, et al. Dravet syndrome seizure frequency and clustering: Placebo-treated patients in clinical trials. Epilepsy Behav. 2024;155:109774. doi: 10.1016/j.yebeh.2024.109774.
Lo Barco T, Kuchenbuch M, Garcelon N, Neuraz A, Nabbout R. Improving early diagnosis of rare diseases using Natural Language Processing in unstructured medical records: an illustration from Dravet syndrome. Orphanet J Rare Dis. 2021;16(309). https://doi.org/10.1186/s13023-021-01936-9.
Strzelczyk A, Schubert-Bast S. Psychobehavioural and cognitive adverse events of anti-seizure medications for the treatment of developmental and epileptic encephalopathies. CNS Drugs. 2022;36(10):1079-1111. doi: 10.1007/s40263-022-00955-9.