UCB (EBR:UCB) FINTEPLA®▼ (fenfluramine) Approved in Japan for the Treatment of Seizures Associated with Dravet Syndrome

Transparency directive : regulatory news

27/09/2022 07:01

https://mb.cision.com/Public/18595/3636902/999776931e930491_800x800ar.png ** FINTEPLA^=C2=AE=E2=96=BC (fenfluramine) Approved in Japan for the Treatm= ent of Seizures Associated with Dravet Syndrome ------------------------------------------------------------ =C2=B7 Approval supported by clinical trial data that showed when added to = existing treatment regimens, fenfluramine significantly reduced monthly con= vulsive seizure frequency compared to placebo^1 =C2=B7 Approval highlights UCB's commitment to expanding global access to f= enfluramine; an estimated 3,000 =E2=80=93 6,000 patients live with Dravet s= yndrome in Japan^2 Brussels (Belgium), 27 September 2022 =E2=80=93 7.00 (CET) =E2=80=93 UCB, a= global biopharmaceutical company, today announced that FINTEPLA^=C2=AE=E2= =96=BC (fenfluramine) oral solution has been approved by the Japanese Minis= try of Health, Labour and Welfare (MHLW) for the treatment of seizures asso= ciated with Dravet syndrome as an add-on therapy to other anti-epileptic me= dicines for patients 2 years of age and older.^3 FINTEPLA^=C2=AE will be av= ailable at all Japanese hospitals and pharmacies. Fenfluramine will be marketed by Nippon Shinyaku Co., Ltd. based on the exc= lusive sales agreement signed in 2019 between Zogenix Inc., (acquired by UC= B in 2022) and Nippon Shinyaku Co., Ltd. UCB is now the Marketing Authoriza= tion holder. =E2=80=9CThis approval in Japan delivers on our commitment towards expandin= g access to new treatment options to address unmet needs of those living wi= th refractory epilepsy across the globe,=E2=80=9D said Charl van Zyl, Execu= tive Vice President, Neurology Solutions, UCB. =E2=80=9CWe would like to th= ank our Japanese patients and families for participating in the clinical tr= ial and making this significant milestone happen so that more people with D= ravet syndrome can help achieve their treatment goals.=E2=80=9D The MHLW approval was based a clinical trial program including data from a = multi-national randomized, double-blind, placebo-controlled study of 143 ch= ildren and young adults (2-18 years) with Dravet syndrome [that included tr= ial participants from Japan], whose seizures were not adequately controlled= with existing anti-epileptic medications. The study showed that when added= to existing treatment regimens, those treated with 0.7 mg/kg day fenfluram= ine experienced a greater reduction (64.8%) in mean monthly convulsive seiz= ures compared to placebo (P <.0001). The median age of patients in the stud= y was 9 years (range, 2=E2=80=9318) and the average baseline convulsive sei= zure frequency across the study groups was approximately 63 seizures per mo= nth. Following a 6-week baseline observation period, patients were randomiz= ed to 1 of 3 treatment groups: 0.7 mg/kg per day (n =3D 49), 0.2 mg/kg per = day (n =3D 46), or placebo (n =3D 48), in which fenfluramine or placebo was= added to each patient=E2=80=99s current treatment regimen of anti-epilepti= c drugs. Patients were titrated to their target dose of fenfluramine over 2= weeks and then remained at that fixed dose for 12 weeks (26-mg maximum dai= ly dose).^1 The incidence of treatment-emergent adverse events was higher in the treatm= ent groups as compared to the placebo group, with 91.7% (n=3D44) of patient= s in the 0.7 mg/kg/day group and 91.3% (n=3D42) of patients in the 0.2 mg/k= g/day group experiencing at least one treatment-emergent adverse event comp= ared to 83.3% (n=3D40) of patients in the placebo group. The incidence of s= erious adverse events was similar in all three groups with 6.3% (n=3D3) of = patients in the 0.7 mg/kg/day group and 6.5% (n=3D3) of patients in the 0.2= mg/kg/day group experiencing at least one treatment-emergent serious adver= se event compared to 4.2% (n=3D2) of patients in the placebo group, includi= ng one placebo patient who died due to SUDEP (sudden unexpected death in ep= ilepsy). Prospective cardiac safety monitoring throughout the study showed = that no study patients developed valvular heart disease or pulmonary arteri= al hypertension.^1 As a condition of regulatory approval in Japan, UCB is required to undertak= e various post-marketing surveillance programs. About Dravet Syndrome=C2=A0 Dravet syndrome is a rare, devastating and life-long form of developmental = and epileptic encephalopathy that generally begins in infancy and is marked= by frequent, treatment-resistant seizures, significant developmental, moto= r, and behavioral impairments, and an increased risk of mortality and sudde= n unexpected death in epilepsy (SUDEP). Most patients follow a course of de= velopmental delay with cognitive, motor and behavioral deficits that persis= t into adulthood. Dravet syndrome severely impacts quality of life for pati= ents, families, and caregivers due to the high physical, emotional, caregiv= ing, and financial burden associated with the disease.^4,5,6 About fenfluramine C-IV Fenfluramine oral solution is a prescription medication used to treat seizu= res associated with Dravet syndrome in patients two years of age and older.= Fenfluramine and the metabolite, norfenfluramine, increase extracellular l= evels of serotonin through interaction with serotonin transporter proteins,= and exhibit agonist activity at serotonin 5HT-2 receptors. ^7,8 Key Safety Information about FINTEPLA^=C2=AE=E2=96=BC in EU^7 Aortic or mitral valvular heart disease and pulmonary arterial hypertension Because of reported cases of valvular heart disease that may have been caus= ed by fenfluramine at higher doses used to treat adult obesity, cardiac mon= itoring must be performed using echocardiography. In the controlled clinica= l studies of fenfluramine for the treatment of Dravet syndrome, no valvular= heart disease was observed. Prior to starting treatment, patients must undergo an echocardiogram to est= ablish a baseline prior to initiating treatment and exclude any pre-existin= g valvular heart disease or pulmonary hypertension. Echocardiogram monitoring should be conducted every 6 months for the first = 2 years and annually thereafter. If an echocardiogram indicates pathologica= l valvular changes, a follow-up echocardiogram should be considered at an e= arlier timeframe to evaluate whether the abnormality is persistent. If path= ological abnormalities on the echocardiogram are observed, it is recommende= d to evaluate the benefit versus risk of continuing fenfluramine treatment = with the prescriber, caregiver, and cardiologist. If treatment is stopped because of aortic or mitral valvular heart disease,= appropriate monitoring and follow-up should be provided in accordance with= local guidelines for the treatment of aortic or mitral valvular heart dise= ase. With past use in higher doses to treat adult obesity, fenfluramine was repo= rted to be associated with pulmonary arterial hypertension. Pulmonary arter= ial hypertension was not observed in the clinical programme, but because of= the low incidence of this disease, the clinical trial experience with fenf= luramine is inadequate to determine if fenfluramine increases the risk for = pulmonary arterial hypertension in patients with Dravet syndrome. If echocardiogram findings are suggestive of pulmonary arterial hypertensio= n, a repeat echocardiogram should be performed as soon as possible and with= in 3 months to confirm these findings. If the echocardiogram finding is con= firmed suggestive of an increased probability of pulmonary arterial hyperte= nsion defined as =E2=80=9Cintermediate probability=E2=80=9D by the 2015 Eur= opean Society of Cardiology (ESC) and the European Respiratory Society (ERS= ) Guidelines, it should lead to a benefit-risk evaluation of continuation o= f Fintepla by the prescriber, carer, and cardiologist. If the echocardiogra= m finding, after confirmation, suggests of a high probability of pulmonary = arterial hypertension, as defined by the 2015 ESC and ERS Guidelines, it is= recommended fenfluramine treatment should be stopped. Decreased appetite and weight loss Fenfluramine can cause decreased appetite and weight loss. An additive effe= ct on decreased appetite can occur when fenfluramine is combined with other= anti-epileptic medicines, for example stiripentol. The decrease in weight = appears to be dose related. Most subjects resumed weight gain over time whi= le continuing treatment. The patient's weight should be monitored. A benefi= t risk evaluation should be undertaken prior to commencing treatment with f= enfluramine in patients with a history of anorexia nervosa or bulimia nervo= sa. 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 phys= icians have been informed of the need for periodic cardiac monitoring in pa= tients taking Fintepla.=C2=A0 Somnolence Fenfluramine can cause somnolence. Other central nervous system depressants, including alcohol, could potentia= te the somnolence effect of fenfluramine. Suicidal behaviour and ideation=C2=A0 Suicidal behaviour and ideation have been reported in patients treated with= anti-epileptic medicines in several indications. A meta-analysis of random= ised placebo-controlled trials with anti-epileptic medicines that did not i= nclude fenfluramine has shown a small increased risk of suicidal behaviour = and ideation. The mechanism of this risk is not known, and the available da= ta do not exclude the possibility of an increased risk for fenfluramine. Pa= tients and caregivers of patients should be advised to seek medical advice = should any signs of suicidal behaviour and ideation emerge. Serotonin syndrome As with other serotonergic agents, serotonin syndrome, a potentially life-t= hreatening condition, may occur with fenfluramine treatment, particularly w= ith concomitant use of other serotonergic agents (including SSRIs, SNRIs, t= ricyclic antidepressants, or triptans); with agents that impair metabolism = of serotonin such as MAOIs; or with antipsychotics that may affect the sero= tonergic neurotransmitter systems. Serotonin syndrome symptoms may include mental status changes (eg, agitatio= n, hallucinations, coma), autonomic instability (eg, tachycardia, labile bl= ood pressure, hyperthermia), neuromuscular aberrations (eg, hyperreflexia, = incoordination), and/or gastrointestinal symptoms (eg, nausea, vomiting, di= arrhoea). If concomitant treatment with fenfluramine and other serotonergic agents th= at may affect the serotonergic systems is clinically warranted, careful obs= ervation of the patient is advised, particularly during treatment initiatio= n and dose increases. Increased seizure frequency As with other anti-epileptic medicines, a clinically relevant increase in s= eizure frequency may occur during treatment with fenfluramine, which may re= quire adjustment in the dose of fenfluramine and/or concomitant anti-epilep= tic medicines, or discontinuation of fenfluramine, should the benefit-risk = be negative.=C2=A0 Cyproheptadine=C2=A0 Cyproheptadine is a potent serotonin receptor antagonist and may therefore = decrease the efficacy of fenfluramine. If cyproheptadine is added to treatm= ent with fenfluramine, patients should be monitored for worsening of seizur= es. If fenfluramine treatment is initiated in a patient taking cyproheptadi= ne, fenfluramine=E2=80=99s 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. Co= nsider discontinuation if there is ocular pain and another cause cannot be = determined. Strong CYP1A2 or CYP2B6 inducers Co-administration with strong CYP1A2 inducers or CYP2B6 inducers may decrea= se fenfluramine plasma concentrations. An increase in fenfluramine dosage s= hould be considered when co-administered with a strong CYP1A2 or CYP2B6 ind= ucer; the maximum daily dose should not be exceeded. Excipients This medicinal product contains sodium ethyl para-hydroxybenzoate (E 215) a= nd sodium methyl para hydroxybenzoate (E 219) which may cause allergic reac= tions (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 med= icinal product. This medicinal product contains less than 1 mmol sodium (23 mg) per the max= imum daily dose of 12 mL, that is to say essentially =E2=80=98sodium-free= =E2=80=99. This medicinal product contains glucose which may be harmful to the teeth. For further safety information and full prescribing information visit: Fint= epla, INN-fenfluramine (europa.eu) (https://www.ema.europa.eu/en/documents/= product-information/fintepla-epar-product-information_en.pdf) Key Safety Information about FINTEPLA^=C2=AE=E2=96=BC in Japan^3 =C2=A0 The administration of fenfluramine, the active ingredient of FINTEPLA, has = been reported to be associated with valvular heart disease and pulmonary ar= terial hypertension. The following monitoring should be performed in collab= oration with a cardiologist. Before starting FINTEPLA treatment, the presence or absence of cardiac dise= ases should be confirmed by echocardiography, etc. During the FINTEPLA treatment period, echocardiography and also adequate ob= servation (e.g., physical findings such as auscultation, chest X-ray, elect= rocardiogram, etc.) should be performed periodically.=C2=A0 If echocardiography reveals any valvular abnormalities, additional echocard= iography should be performed to make sure the abnormality does not persist.= If echocardiography reveals findings indicative of valvular heart disease = or pulmonary arterial hypertension, a decision on whether FINTEPLA can be a= dministered should be reached based on a careful consideration of the risks= and benefits for initiating or continuing treatment. =C2=A0 FINTEPLA can cause decreased appetite. Patients and their caregivers should= be thoroughly informed in advance and instructed to visit their physicians= if necessary. Since weight loss may occur, patients should be carefully mo= nitored during treatment with this product, including periodic weigh-ins, a= nd if weight loss is observed, a dosage reduction should be considered. Since FINTEPLA may cause drowsiness and impaired attention, concentration, = and reflex-motor skills, advise patients and caregiver should be cautioned = that patients taking FINTEPLA should not drive a car or operate other hazar= dous machineries. Fenfluramine can cause mydriasis and can precipitate angle closure glaucoma= . Consider discontinuing treatment with FINTEPLA in patients with acute dec= reases in visual acuity or ocular pain. When discontinuing FINTEPLA, the dose should be reduced gradually to minimi= ze the risk of increased seizure frequency and status epilepticus. For further safety information and full Japanese prescribing information vi= sit: =E3=83=95=E3=82=A3=E3=83=B3=E3=83=86=E3=83=97=E3=83=A9=E5=86=85=E7=94= =A8=E6=B6=B22.2mg/mL (pmda.go.jp) (https://www.info.pmda.go.jp/go/pack/1139= 0B0S1026_1_01/?view=3Dframe&style=3DXML&lang=3Dja) ^=E2=96=BCThis medicinal product is subject to additional monitoring. This = will allow quick identification of new safety information. Healthcare profe= ssionals are asked to report any suspected adverse reactions. For further information, contact UCB:=C2=A0 Media/Corporate Communications=C2=A0 Laurent Schots T +32 2 559 9264 | laurent.schots@ucb.com Nick Francis T +44 7769 307745 | nick.francis@ucb.com Investor Relations Antje Witte, Investor Relations, UCB T +32.2.559.9414 antje.witte@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 soluti= ons to transform the lives of people living with severe diseases of the imm= une system or of the central nervous system. With more than 7 600 people in= approximately 40 countries, the company generated revenue of =E2=82=AC5.3 = billion in 2020. UCB is listed on Euronext Brussels (symbol: UCB). Follow u= s on Twitter: @UCB_news Forward looking statements=C2=A0 This press release contains forward-looking statements including, without l= imitation, statements containing the words "believes", "anticipates", "expe= cts", "intends", "plans", "seeks", "estimates", "may", "will", "continue" a= nd similar expressions. These forward-looking statements are based on curre= nt plans, estimates and beliefs of management. All statements, other than s= tatements of historical facts, are statements that could be deemed forward-= looking statements, including but not limited to, the ability of UCB to suc= cessfully integrate the operations of Zogenix as planned or at all, estimat= es of revenues, operating margins, capital expenditures, cash, other financ= ial information, expected legal, arbitration, political, regulatory or clin= ical results or practices and other such estimates and results. By their na= ture, such forward-looking statements are not guarantees of future performa= nce and are subject to known and unknown risks, uncertainties and assumptio= ns which might cause the actual results, financial condition, performance o= r achievements of UCB, or industry results, to differ materially from those= that may be expressed or implied by such forward-looking statements contai= ned in this press release. Important factors that could result in such diff= erences include: the global spread and impact of COVID-19, changes in gener= al economic, business and competitive conditions, the inability to obtain n= ecessary regulatory approvals or to obtain them on acceptable terms or with= in 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, safet= y, quality, data integrity or manufacturing issues; potential or actual dat= a security and data privacy breaches, or disruptions of our information tec= hnology systems, product liability claims, challenges to patent protection = for products or product candidates, competition from other products includi= ng biosimilars, changes in laws or regulations, exchange rate fluctuations,= changes or uncertainties in tax laws or the administration of such laws, a= nd hiring and retention of its employees. There is no guarantee that new pr= oduct candidates will be discovered or identified in the pipeline, or that = new indications for existing products will be developed and approved. Movem= ent 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 v= aried in the past and UCB expects similar unpredictability going forward. P= roducts 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 success= ful 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 a= t the moment of acquisition. Also, UCB or others could discover safety, sid= e effects or manufacturing problems with its products and/or devices after = they are marketed. The discovery of significant problems with a product sim= ilar to one of UCB's products that implicate an entire class of products ma= y have a material adverse effect on sales of the entire class of affected p= roducts. Moreover, sales may be impacted by international and domestic tren= ds toward managed care and health care cost containment, including pricing = pressure, political and public scrutiny, customer and prescriber patterns o= r practices, and the reimbursement policies imposed by third-party payers a= s 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 availab= ility of UCB's data and systems. Given these uncertainties, you should not place undue reliance on any of su= ch forward-looking statements. There can be no guarantee that the investiga= tional or approved products described in this press release will be submitt= ed or approved for sale or for any additional indications or labelling in a= ny market, or at any particular time, nor can there be any guarantee that s= uch products will be or will continue to be commercially successful in the = future. UCB is providing this information, including forward-looking statements, on= ly 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-lookin= g statements with regard thereto or any change in events, conditions or cir= cumstances on which any such statement is based, unless such statement is r= equired pursuant to applicable laws and regulations. Additionally, information contained in this document shall not constitute a= n 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 jurisdi= ction in which such offer, solicitation or sale would be unlawful prior to = the registration or qualification under the securities laws of such jurisdi= ction. FINTEPLA^=C2=AE and Zogenix, Inc. are registered trademarks of the UCB Grou= p of Companies. References 1. UCB Data on File. Sullivan, J. AES. 2020. Poster 853. 2. Yamada M, Suzuki K, Matsui D, Inoue Y, Ohtsuka Y. Long-term safety and e= ffectiveness of stiripentol in patients with Dravet syndrome: Interim repor= t of a post-marketing surveillance study in Japan. Epilepsy Res. 2021;170:1= 06535. 3. Fintepla Japan PI. September 2022. =E3=83=95=E3=82=A3=E3=83=B3=E3=83=86= =E3=83=97=E3=83=A9=E5=86=85=E7=94=A8=E6=B6=B22.2mg/mL (pmda.go.jp) (https:/= /www.info.pmda.go.jp/go/pack/11390B0S1026_1_01/?view=3Dframe&style=3DXML&la= ng=3Dja) . Accessed September 2022 4. Dravet C. The Core Dravet Syndrome Phenotype. Epilepsia. 2011 Apr;52 Sup= pl 2:3-9. 5. Dravet C. Dravet syndrome history. Dev Med Child Neurol. 2011 Apr;53 Sup= pl 2:1-6. 6. Wu YW, Sullivan J, McDaniel SS, et al. Incidence of Dravet Syndrome in t= he US Population. Pediatrics. 2015 Nov;136(5):e1310-1315. 7. Fintepla EMEA SmPC.https://www.ema.europa.eu/en/documents/product-inform= ation/fintepla-epar-product-information_en.pdf. Accessed September 2022 8. Fintepla=C2=AE US PI. https://www.accessdata.fda.gov/drugsatfda_docs/lab= el/2020/212102s000lbl.pdf. Accessed September 2022 GenericFile Japan approval of FINTEPLA- Press Release Approved ENG (https://mb.cision.c= om/Public/18595/3636902/bc76b4f66c7a4a3f.pdf) ______________________ If you would rather not receive future communications from UCB SA, please g= o to https://eu.vocuspr.com/OptOut.aspx?2973226x20421x117072x1x6868579x2400= 0x6&Email=3Dregnews%40symexglobal.com. UCB SA, All=C3=A9e de la Recherche, 60 ., Brussels, . B - 1070 Belgium

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UCB (EBR:UCB) FINTEPLA®▼ (fenfluramine) Approved in Japan for the Treatment of Seizures Associated with Dravet Syndrome

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