Dextromethorphan Hydrobromide Hydrate

FINTEPLA is approved by the U.S. Food and Drug Administration (FDA) for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome in patients two years of age and older1 Data showed a clinically significant reduction in generalized tonic-clonic seizures (GTCS) and tonic-clonic seizures (TCS) from baseline in patients with developmental and epileptic encephalopathies (DEEs)2 ATLANTA, June 24, 2024 /PRNewswire/ -- UCB, a global biopharmaceutical company, today announced that Epilepsia published findings from a comprehensive scoping review examining the efficacy of FINTEPLA ® (fenfluramine) in reducing the frequency of generalized tonic-clonic seizures (GTCS) and tonic-clonic seizures (TCS) among patients with developmental and epileptic encephalopathies (DEEs). This analysis highlighted a significant reduction in both GTCS and TCS across various DEEs adding to the already established data from the FINTEPLA clinical trial program.2 FINTEPLA® (fenfluramine) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome in patients two years of age and older. Using the Preferred Reporting Items for Systematic Review and Meta-Analyses extension for Scoping Review (PRISMA-ScR) guidelines, a comprehensive search of five literature databases was conducted up to February 14, 2023 for studies that reported change in GTCS or TCS after treatment with FINTEPLA. Out of 422 studies, 14 met the eligibility criteria, identifying 421 unique patients with conditions including Dravet syndrome (DS), CDKL5 deficiency disorder, SCN8A-related disorder, Lennox-Gastaut syndrome (LGS), SCN1B-related disorder, and other DEEs.2 Nine of the 14 studies were on DS, 1 was on LGS and 4 small studies investigated other DEEs.2 In patients receiving FINTEPLA, the median reduction from baseline in GTCS or TCS frequency ranged from 47.2% to 100%.2 The analysis further demonstrated that following treatment with FINTEPLA, 72% of patients in 10 studies (n=144) achieved ≥50% reduction in GTCS or TCS from baseline.2 Additionally, in nine studies (n=112), 54% and 29% of patients achieved ≥75% and 100% reduction in GTCS or TCS from baseline, respectively.2 "Improving seizure control, especially of the most severe seizures, could mitigate neurodevelopmental delay, improve quality of life, minimize polypharmacy, and reduce injury and premature death, namely sudden unexpected death in epilepsy (SUDEP)," said Dr. Kelly Knupp, pediatric neurologist, Associate Professor of Pediatrics and Neurology, University of Colorado. "This analysis, coupled with established data from the FINTEPLA clinical trial program, positions FINTEPLA to be a promising future option for the management of various DEEs." DEEs, such as DS and LGS, are a severe group of rare epilepsy disorders that are characterized by pharmacoresistant seizures as well as encephalopathy, or significant developmental delay or loss of developmental skills, and are often challenging to diagnose.3,4 Patients with DEEs often experience multiple seizure types, including TCS that can be GTCS or focal evolving to bilateral tonic-clonic (FBTCS).5 The impact of DEEs also reaches far beyond seizures, with a wide range of non-seizure clinical manifestations, including intellectual disability, motor and movement disorders, and sleep issues.3,6 "For people and caregivers impacted by DEEs such as DS and LGS, the ability to effectively manage seizures is critical. These findings reinforce the potential of FINTEPLA in reducing seizure frequency among patients with DEEs," said Rebecca Burns, PharmD, PhD, Medical Strategy Lead, Epilepsy and Rare Syndromes, UCB. "The publication of these results underscores our commitment to bringing improvements to the lives of those impacted by rare epilepsies as we leverage today's expertise for a better tomorrow." 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 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 . Please see full Prescribing Information , including Boxed Warning, for additional Important Safety Information. About Epilepsy Epilepsy is a common neurological condition worldwide and affects approximately 50 million people.7 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.8 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. About UCB UCB, Brussels, Belgium () 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. For further information, contact UCB: Investor Relations Antje Witte T: +32.2.559.94.14 email [email protected] US Communications Becky Malone T +1.919.605.9600 Email [email protected] 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. 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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. Gil-Nagel A, Cross JH, Devinsky O, et al. Comprehensive Scoping Review of Fenfluramine's Role in Managing Generalized Tonic-Clonic Seizures in Developmental and Epileptic Encephalopathies. Epilepsia. 2024. Chang YT, Hong SY, Lin WD, Lin CH, Lin SS, Tsai FJ, Chou IC. Genetic Testing in Children with Developmental and Epileptic Encephalopathies: A Review of Advances in Epilepsy Genomics. Children (Basel). 2023;10(3):556. doi:10.3390/children10030556. Lo Barco T, Kuchenbuch M, Garcelon N, et al. 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). Raga S, Specchio N, Rheims S, Wilmshurst JM. Developmental and epileptic encephalopathies: recognition and approaches to care. Epileptic Disord. 2021;23(1):40-52. doi: 10.1684/epd.2021.1244. 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. Meyer AC, Dua T, Ma J, et al. Global disparities in the epilepsy treatment gap: a systemic review. Bull World Health Organ. 2010;88:260-266. National Institute of Neurological Disorders and Stroke. (2023). Epilepsy and Seizures. U.S. Department of Health and Human Services, National Institutes of Health. Retrieved June 2, 2024. US-FA-2400276 Date of preparation: June 2024 FINTEPLA® is a registered trademark of the UCB Group of Companies. ©2024 UCB, Inc., Smyrna, GA 30080. All rights reserved. SOURCE UCB