FINTEPLA® (fenfluramine) Oral Solution Now FDA Approved for Treatment of Seizures Associated with Lennox-Gastaut Syndrome (LGS)

• FINTEPLA^® has demonstrated efficacy in the most difficult-to-treat seizure types,^1,2 including drop seizures, which cause a person to suddenly lose muscle tone, become limp, and fall to the ground, with a high likelihood of injury³
• LGS is a severe childhood-onset developmental and epileptic encephalopathy characterized by drug-resistant seizures with high morbidity⁴ as well as serious impairment of neurodevelopmental, cognitive, and motor functions.⁵ LGS affects an estimated 30,000 – 50,000 patients in the U.S.⁶
• Approval highlights UCB's commitment to bringing differentiated medicines to specific epilepsy patient populations where there is a high unmet need

BRUSSELS and ATLANTA, March 28, 2022 /PRNewswire/ -- UCB (Euronext: UCB), a global biopharmaceutical company, today announced that FINTEPLA^® (fenfluramine) oral solution CIV has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of seizures associated with Lennox-Gastaut syndrome in patients two years of age and older. It is already approved for the treatment of seizures associated with Dravet syndrome (DS) in patients two years of age and older.¹ Additionally, the FDA granted FINTEPLA pediatric exclusivity. FINTEPLA for LGS is available through a restricted distribution program, called the FINTEPLA Risk Evaluation and Mitigation Strategy (REMS) Program. FINTEPLA was developed by Zogenix, Inc., which was recently acquired by UCB.

LGS is a severe childhood-onset developmental and epileptic encephalopathy (DEE) characterized by drug-refractory seizures with high morbidity⁴ as well as serious impairment of neurodevelopmental, cognitive, and motor functions.⁵ LGS affects an estimated 30,000 – 50,000 patients in the U.S.⁶ LGS has far-reaching effects beyond seizures, including issues with communication, psychiatric symptoms, sleep, behavioral challenges, and mobility.⁷ Additionally, sudden unexpected death in epilepsy (SUDEP) is a major concern for people living with LGS.⁸

FINTEPLA has demonstrated efficacy in the most difficult to treat seizure types,^1,2 including drop seizures, which cause a person to suddenly lose muscle tone, become limp, and fall to the ground, with a high likelihood of injury.³ FINTEPLA has a mechanism of action different from and complementary to current seizure medications, and it can be used with no disruptions to current antiseizure regimens.⁹ In the global placebo-controlled Phase 3 clinical study, there were numerically greater improvements on the Clinical Global Impressions scale (CG-I) in patients living with LGS when taking FINTEPLA.¹

"The approval of FINTEPLA for Lennox-Gastaut syndrome highlights our continued commitment to bringing differentiated medicines to patients who may not be well controlled on current therapies, and their caregivers," said Mike Davis, Head of Global Epilepsy, UCB, Inc. "We are proud to add FINTEPLA as a treatment for Dravet syndrome, and now Lennox-Gastaut syndrome, to our portfolio of epilepsy medicines to help reduce the impact and burden of seizures, including severe epilepsy syndromes that have high pediatric morbidity and mortality rates."

The FDA approval was supported by safety and efficacy data from a global, randomized, placebo-controlled Phase 3 clinical trial in 263 patients with LGS (age 2-35 years), which demonstrated that FINTEPLA at a dose of 0.7 mg/kg/day significantly reduced monthly drop seizures frequency by a median of 23.7% from baseline compared to 8.7% placebo (p=0.0037). Nearly a fourth of those patients on FINTEPLA 0.7 mg/kg/day experienced a ≥50% reduction in drop seizure frequency per 28 days; 18% with ≥50% to <75% reduction and 6% ≥75% reduction.¹ The common adverse reactions that occurred in patients treated with FINTEPLA (incidence at least 10% and greater than placebo) were diarrhea, decreased appetite, fatigue, somnolence, and vomiting. The FINTEPLA safety database includes long-term cardiovascular safety data for patients treated for up to three years in DS and LGS.¹

"LGS is one of the most challenging epileptic encephalopathies to treat, and the vast majority of patients are not well controlled, despite a regimen of multiple antiepileptic drugs," said Kelly Knupp, M.D., MSCS, FAES, Associate Professor, Children's Hospital Colorado. "As a complementary therapy, FINTEPLA offers a different mechanism of action and demonstrated ability to significantly reduce the number of seizures associated with a drop, a critical measure for managing this severe form of epilepsy."

UCB is committed to supporting patient access to FINTEPLA, and as part of that commitment, Zogenix Central, a comprehensive support program, will provide ongoing product assistance to patients, caregivers, and their medical teams. Further information is available at www.FINTEPLA.com.

"LGS is a severe, life-long disease with wide-ranging effects beyond seizures. It impacts every aspect of daily life and puts great strain on the entire family. There is a desperate need for more effective treatment options," said Dr. Tracy Dixon-Salazar, Executive Director of the Lennox-Gastaut Syndrome Foundation and mother to an adult daughter with LGS. "The potential for FINTEPLA to make a difference in the daily, horrific seizures we are dealing with in LGS cannot be understated. We are so grateful for the researchers who have worked so hard to help all of us suffering at the hands of LGS."

UCB acquired Zogenix and FINTEPLA on March 7, 2022. The acquisition is consistent with UCB's sustainable patient value strategy and continued commitment to providing world-leading patient value to all people living with epilepsy, with an increasing focus on creating value and new solutions that address the unmet needs of people with certain specialized or rare types of epilepsy, where few or no options exist.

About FINTEPLA^® (fenfluramine) C-IV

FINTEPLA^® (fenfluramine) oral solution is a prescription medication approved by the FDA and EMA, and under regulatory review with PMDA (Japan), for the treatment of seizures associated with Dravet syndrome in patients two years of age and older.^10,11 A Type II Variation Application for treatment of seizures associated with LGS has also been submitted to the European Medicines Agency (EMA).¹²

In the United States, FINTEPLA is available only through a restricted distribution program called the FINTEPLA REMS program. FINTEPLA is available in Europe under a controlled access program requested by the EMA to prevent off-label use for weight management and to confirm that prescribing physicians have been informed of the need for periodic cardiac monitoring in patients taking FINTEPLA. Further information is available at www.FinteplaREMS.com or by telephone at +1 877 964 3649.

Please see full Prescribing Information, including Boxed Warning, for additional important information on FINTEPLA.

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 >35mmHg).

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 valvular heart disease and pulmonary arterial hypertension, how to recognize signs and symptoms of valvular heart disease and pulmonary arterial hypertension, 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

Administration to patients with hepatic impairment is not recommended.

To report SUSPECTED ADVERSE REACTIONS, contact Zogenix Inc. at 1-866-964-3649 (1-866-Zogenix) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information, including Boxed Warning, for additional important information on FINTEPLA.

For further information, contact UCB:

Investor Relations
Antje Witte
T +32.2.559.9414
[email protected]

Corporate Communications
Erica Puntel, U.S. Media Relations
T +404 938 5359
[email protected]

Laurent Schots, Media Relations
T+32.2.559.9264
[email protected]   

Nick Francis
T +44 7769 307745
[email protected]

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 8 600 people in approximately 40 countries, the company generated revenue of € 5.8 billion in 2021. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCB_news.

Forward looking statements

This press release contains 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 but not limited to, the ability of UCB to successfully integrate the operations of Zogenix as planned or at all, 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: the global spread and impact of COVID-19, 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, 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' 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 and 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.

FINTEPLA^® and Zogenix, Inc. are registered trademarks of the UCB Group of Companies.

©2022 UCB, Inc., Smyrna, GA 30080. All rights reserved. US-P-OT--2200016.

SOURCE UCB, Inc.

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