UCB (EBR:UCB) UCB Media Room: U.S. FDA acceptance of new drug application and EMA MAA validation for zilucoplan for the treatment of generalized myasthenia gravis in adult patients

Transparency directive : regulatory news

14/11/2022 07:01

https://mb.cision.com/Public/18595/3666193/9cece37fb36d9bab_800x800ar.png ** UCB announces U.S. FDA acceptance of new drug application and EMA MAA va= lidation for zilucoplan for the treatment of generalized myasthenia gravis = in adult patients ------------------------------------------------------------ =C2=B7 New drug application (NDA) for zilucoplan seeks approval for the tre= atment of generalized myasthenia gravis (gMG) in adult patients who are ace= tylcholine receptor antibody positive (AChR-Ab+)=C2=A0 =C2=B7 Acceptance by U.S. Food and Drug Administration (FDA) follows the re= cent European Medicines Agency (EMA) validation of Marketing Authorization = Application (MAA) for treatment of adult patients with AChR-Ab+ gMG and who= require treatment in addition to steroids or non-steroidal immunosuppressa= nts=C2=A0 =C2=B7 Both NDA and MAA are based on pivotal Phase 3 RAISE study in gMG, wh= ich demonstrated treatment with zilucoplan resulted in clinically meaningfu= l and statistically significant improvements in key MG-specific outcomes co= mpared to placebo =C2=B7 UCB expects to receive feedback from the agencies in Q4 of 2023=C2= =A0 Brussels (Belgium), 14 November 2022 =E2=80=93 7:00 (CEST) =E2=80=93 UCB, a= global biopharmaceutical company, today announced that the U.S. Food and D= rug Administration (FDA) has accepted for review the New Drug Application (= NDA) for its investigational treatment, zilucoplan.=C2=A0 Zilucoplan is a subcutaneous (SC), self-administered peptide inhibitor of c= omplement component 5 (C5 inhibitor) for the treatment of adult patients wi= th acetylcholine receptor antibody positive (AChR-Ab+) generalized myasthen= ia gravis (gMG).=C2=A0 In 2019, the U.S. FDA granted orphan drug designation to zilucoplan for the= treatment of MG.^1 The safety and efficacy of zilucoplan have not been est= ablished and it is not currently approved for use in any indication by any = regulatory authority worldwide. This acceptance follows the recent European Medicines Agency (EMA) validati= on of the Marketing Authorization Application (MAA) for zilucoplan for the = treatment of adult patients with AChR-Ab+ gMG and who require treatment in = addition to steroids or non-steroidal immunosuppressants. Validation confir= ms that the application is complete and the formal review process by the EM= A=E2=80=99s Committee for Medicinal Products for Human Use (CHMP) can begin= . Orphan designation was granted in 2022 by the European Commission to zilu= coplan for the treatment of myasthenia gravis.^2 gMG is a chronic and unpredictable auto-immune disease in which pathogenic = autoantibodies can impair synaptic transmission at the neuromuscular juncti= on by targeting specific proteins on the post-synaptic membrane. This disru= pts the ability of the nerves to stimulate the muscle and results in a weak= er contraction.^4 People living with MG can experience a variety of symptom= s, including drooping eyelids, double vision, and difficulty in swallowing,= chewing and talking, as well as severe muscle weakness that can result in = life-threatening weakness of the muscles of respiration.^3 In the U.S. the = prevalence of MG is estimated at 14 to 20 per 100,000 population; approxima= tely 36,000 to 60,000 cases.^4 In Europe, the prevalence is estimated at 10= per 100,000 population.^5 =E2=80=9CPeople living with gMG experience high treatment burden, on top of= the debilitating impact of the condition, and there is a clear need for ad= ditional targeted treatments to support the gMG community. Our goal is to p= rovide a solution that can help meet these needs and transform lives,=E2=80= =9D said Charl van Zyl, Executive Vice President Neurology Solutions & Head= of EU/International Markets, UCB. =E2=80=9CThe acceptance of the NDA by th= e FDA as well as the acceptance of the MAA by the EMA, brings us one step f= urther on our journey towards approval for this medicine. We look forward t= o working with the FDA and EMA to help bring this important new treatment o= ption to patients.=E2=80=9D The NDA and MAA are based on data from the pivotal Phase 3 RAISE study (NCT= 04115293), which demonstrated at week 12 that treatment with zilucoplan (0.= 3 mg/kg daily) resulted in clinically meaningful and statistically signific= ant improvements in key gMG-specific outcomes compared with placebo in pati= ents with AChR-Ab+ gMG. The study met its primary endpoint with zilucoplan = showing a placebo-corrected mean improvement of 2.09 points in the Myasthen= ia Gravis Activities of Daily Living (MG-ADL) score at week 12 (p<0.001).^6 Zilucoplan demonstrated a favorable safety and tolerability profile, showin= g a similar rate of treatment-emergent adverse events (TEAEs) between ziluc= oplan (76.7%) and placebo (70.5%). The most common TEAEs were injection sit= e bruising, headache, and diarrhea. Rates of treatment discontinuation due = to a TEAE were low and all patients who completed the 12-week treatment per= iod have entered the ongoing RAISE-XT open-label extension study (NCT042258= 71).^6,7 In the RAISE study, 174 adult patients were randomised to receive daily SC,= self-administered doses of placebo (N=3D88) or zilucoplan 0.3 mg/kg (N=3D8= 6). Patient demographics and baseline disease characteristics were generall= y balanced between treatment arms.^6 As a complement C5 inhibitor, zilucoplan is a targeted therapy that inhibit= s key components in the underlying pathophysiology of gMG, addressing the u= nderlying mechanism of neuromuscular junction damage.^8,9 =E2=80=9CWe are deeply committed to improving outcomes for the gMG communit= y. People who live with gMG suffer unpredictable, fluctuating, and debilita= ting symptoms, which have a huge impact on their lives. We want to help red= uce the day-to-day burden of this challenging disease,=E2=80=9D said Iris L= oew-Friedrich, Executive Vice-President and Chief Medical Officer at UCB. = =E2=80=9CIf approved, zilucoplan has the potential to address the unmet nee= d for people with gMG by providing targeted improvements in signs and sympt= oms of gMG disease activity and severity. A benefit of targeted treatment i= s that it may help reduce the adverse events that can be associated with no= n-specific immunosuppressive treatment of gMG.=E2=80=9D=C2=A0 UCB anticipates making regulatory filings for zilucoplan in gMG in Great Br= itain, Japan, and rest of the world from Q3 2022 onwards.=C2=A0 Alongside zilucoplan, UCB is also investigating rozanolixizumab, a SC-admin= istered, humanized monoclonal antibody that specifically binds, with high a= ffinity, to human neonatal Fc receptor (FcRn), as a potential treatment for= gMG. UCB anticipates filing regulatory submissions for rozanolixizumab lat= er this year.=C2=A0 For further information, contact UCB:=C2=A0 Brand Communications, Rare Diseases Jim Baxter T+32.2.473.78.85.01=C2=A0 jim.baxter@ucb.com=C2=A0 Corporate Communications, Media Relations Laurent Schots=C2=A0 T+32.2.559.92.64 =C2=A0 Laurent.schots@ucb.com=C2=A0 Investor Relations Antje Witte =C2=A0 =C2=A0 =C2=A0 =C2=A0=C2=A0 T +32.2.559.94.14=C2=A0 antje.witte@ucb.com About Generalized Myasthenia Gravis (gMG) Myasthenia gravis is a rare disease impacting more than 700,000 people worl= dwide.^11 People living with gMG can experience a variety of symptoms, incl= uding drooping eyelids, double vision, difficulty swallowing, chewing and t= alking, as well as severe muscular weakness that can result in life threate= ning weakness of the muscles of respiration.^3, 4 gMG is a chronic and unpredictable auto-immune disease in which pathogenic = autoantibodies can impair synaptic transmission at the neuromuscular juncti= on (NMJ) by targeting specific proteins on the post-synaptic membrane. This= disrupts the ability of the nerves to stimulate the muscle and results in = a weaker contraction.^4,12=C2=A0gMG can occur in any race, although previou= s studies have shown that women are more often impacted than men.^13,14=C2= =A0 Most patients with gMG have pathogenic IgG antibodies that disrupt the = transmission of nerve impulses to muscles in the NMJ and some activate the = complement cascade.^15=C2=A0 Complement-mediated destruction via MAC format= ion is a key mechanism causing damage at the NMJ and is the key driver of d= isease in AChR-Ab+ gMG. About the zilucoplan RAISE study ^6,7 The RAISE study (NCT04115293) is a multi-center, Phase 3, randomized, doubl= e-blind, placebo-controlled study to confirm the efficacy, safety, and tole= rability of zilucoplan in patients with AChR-Ab+ gMG. Patients were randomi= zed in a 1:1 ratio to receive daily subcutaneous (SC) doses of 0.3 mg/kg zi= lucoplan or placebo for 12 weeks. The primary endpoint for the RAISE study is change from baseline to Week 12= in the Myasthenia Gravis-Activities of Daily Living (MG-ADL) score. Second= ary endpoints include change in the Quantitative Myasthenia Gravis (QMG) sc= ore, the Myasthenia Gravis Composite (MGC) and the Myasthenia Gravis Qualit= y of Life 15 revised (MG-QoL15r) score from baseline to Week 12, =C2=A0time= to rescue therapy, the proportion with minimal symptom expression (MSE) (d= efined as MG-ADL of 0 or 1), the proportion with a =E2=89=A53-point reducti= on in MG-ADL and the proportion with a =E2=89=A55-point reduction in QMG wi= thout rescue therapy, all measured at Week 12. The secondary safety endpoin= t is incidence of TEAEs. Patients who completed the 12 week RAISE trial had= the possibility to enter the open label extension study, RAISE-XT.=C2=A0 For more information about the trial visit https://clinicaltrials.gov/ct2/s= how/NCT04115293.=C2=A0 About Zilucoplan=C2=A0 Zilucoplan is a once-daily SC, self-administered peptide inhibitor of compl= ement component 5 (C5 inhibitor) under clinical development by UCB in gMG. = As a C5 inhibitor, zilucoplan inhibits complement-mediated damage to the ne= uromuscular junction through its targeted dual mechanism of action.^9 In 20= 19, the US FDA granted orphan drug designation to zilucoplan for the treatm= ent of myasthenia gravis.^1 Orphan designation was granted in 2022 by the E= uropean Commission to zilucoplan for the treatment of myasthenia gravis.^2 The safety and efficacy of zilucoplan have not been established and it is n= ot currently approved for use in any indication by any regulatory authority= worldwide. About Rozanolixizumab Rozanolixizumab is an SC administered, humanized monoclonal antibody that s= pecifically binds, with high affinity, to human neonatal Fc receptor (FcRn)= . It has been designed to block the interaction of FcRn and Immunoglobulin = G (IgG), accelerating the catabolism of antibodies and reducing the concent= ration of pathogenic IgG autoantibodies.^16,15 Rozanolixizumab is under clinical development with the aim of improving the= lives of people with pathogenic IgG-autoantibody-driven autoimmune disease= s. In 2019, the US FDA granted orphan drug designation to rozanolixizumab f= or the treatment of myasthenia gravis.^17 Orphan designation was granted in= 2020^18 by the European Commission for rozanolixizumab to the treatment of= myasthenia gravis. The safety and efficacy of rozanolixizumab have not been established and it= is not approved for use in any indication by any regulatory authority worl= dwide. About UCB in Rare Diseases=C2=A0 At UCB, we don=E2=80=99t just see patients or population sizes, we see peop= le in need. Through decades of serving the neurology and immunology communi= ties, we have improved lives with impactful medicines and by enhancing the = social and emotional well-being of patients. As a continuation of our herit= age, we are now expanding our efforts to tackle rare neurological and immun= ological diseases where current options offer little hope, including invest= igational treatments for gMG, myelin oligodendrocyte glycoprotein antibody-= associated disease (MOG-AD) and autoimmune enteropathy (AIE). About UCB=C2=A0 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, UCB generated revenue of =E2=82=AC5.3 billion = in 2020. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twi= tter: @UCB_news Forward looking statements=C2=A0 This press release may contain forward-looking statements including, withou= t limitation, statements containing the words =E2=80=9Cbelieves=E2=80=9D, = =E2=80=9Canticipates=E2=80=9D, =E2=80=9Cexpects=E2=80=9D, =E2=80=9Cintends= =E2=80=9D, =E2=80=9Cplans=E2=80=9D, =E2=80=9Cseeks=E2=80=9D, =E2=80=9Cestim= ates=E2=80=9D, =E2=80=9Cmay=E2=80=9D, =E2=80=9Cwill=E2=80=9D, =E2=80=9Ccont= inue=E2=80=9D and similar expressions. These forward-looking statements are= based on current plans, estimates and beliefs of management. All statement= s, other than statements of historical facts, are statements that could be = deemed forward-looking statements, including estimates of revenues, operati= ng margins, capital expenditures, cash, other financial information, expect= ed legal, arbitration, political, regulatory or clinical results or practic= es and other such estimates and results. By their nature, such forward-look= ing statements are not guarantees of future performance and are subject to = known and unknown risks, uncertainties and assumptions which might cause th= e 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 relea= se. Important factors that could result in such differences include: the gl= obal spread and impact of COVID-19, changes in general economic, business a= nd competitive conditions, the inability to obtain necessary regulatory app= rovals or to obtain them on acceptable terms or within expected timing, cos= ts associated with research and development, changes in the prospects for p= roducts in the pipeline or under development by UCB, effects of future judi= cial decisions or governmental investigations, safety, quality, data integr= ity or manufacturing issues; potential or actual data security and data pri= vacy breaches, or disruptions of our information technology systems, produc= t 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 uncertainti= es 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 b= e discovered or identified in the pipeline, will progress to product approv= al or that new indications for existing products will be developed and appr= oved. Movement from concept to commercial product is uncertain; preclinical= results do not guarantee safety and efficacy of product candidates in huma= ns. So far, the complexity of the human body cannot be reproduced in comput= er models, cell culture systems or animal models. The length of the timing = to complete clinical trials and to get regulatory approval for product mark= eting has varied in the past and UCB expects similar unpredictability going= forward. Products or potential products which are the subject of partnersh= ips, joint ventures or licensing collaborations may be subject to differenc= es 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 pa= rtnership. UCB=E2=80=99 efforts to acquire other products or companies and = to integrate the operations of such acquired companies may not be as succes= sful as UCB may have believed at the moment of acquisition. Also, UCB or ot= hers could discover safety, side effects or manufacturing problems with its= products and/or devices after they are marketed. The discovery of signific= ant problems with a product similar to one of UCB=E2=80=99s products that i= mplicate an entire class of products may have a material adverse effect on = sales of the entire class of affected products. Moreover, sales may be impa= cted by international and domestic trends toward managed care and health ca= re cost containment, including pricing pressure, political and public scrut= iny, customer and prescriber patterns or practices, and the reimbursement p= olicies imposed by third-party payers as well as legislation affecting biop= harmaceutical pricing and reimbursement activities and outcomes. Finally, a= breakdown, cyberattack or information security breach could compromise the= confidentiality, integrity and availability of UCB=E2=80=99s data and syst= ems. 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 it does not reflect any potenti= al impact from the evolving COVID-19 pandemic, unless indicated otherwise. = UCB is following the worldwide developments diligently to assess the financ= ial significance of this pandemic to UCB. UCB expressly disclaims any duty = to update any information contained in this press release, either to confir= m the actual results or to report or reflect any change in its forward-look= ing statements with regard thereto or any change in events, conditions or c= ircumstances 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 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 regis References: 1. US Food and Drug Administration https://www.accessdata.fda.gov/scripts/o= pdlisting/oopd/detailedIndex.cfm?cfgridkey=3D699319. Accessed October 2022 2. Data on file. 3. Hansen JS, et al. Mortality in myasthenia gravis: A nationwide populatio= n-based follow-up study in Denmark. Muscle Nerve. 2016;53:73-77. 4. Myasthenia Gravis Foundation of America. Clinical Overview of MG. https:= //myasthenia.org/Professionals/Clinical-Overview-of-MG. Accessed August 202= 2=C2=A0 5. Salari N, et al. Global prevalence of myasthenia gravis and the effectiv= eness of common drugs in its treatment: a systematic review and meta-analys= is. J Transl Med 19, 516 (2021). https://doi.org/10.1186/s12967-021-03185-7= . Accessed September 2022. 6. Vu T, et al. Efficacy and safety of zilucoplan in myasthenia gravis: Res= ponder analysis from the randomized Phase 3 RAISE trial. Poster 200, AANEM = 2022. 7. Weiss MD, et al, Quality of life outcomes in RAISE: A double-blind rando= mized, placebo-controlled study of zilucoplan in gMG. Oral presentation. MG= FA Scientific Session, AANEM 2022. 8. Tannemaat et al. Emerging therapies for autoimmune myasthenia gravis: To= wards treatment without corticosteroids. Neuromuscul Disord. 2020;30(2):111= -119 9. Howard J, et al. Clinical Effects of the Self-administered Subcutaneous = Complement Inhibitor Zilucoplan in Patients With Moderate to Severe General= ized Myasthenia Gravis: Results of a Phase 2 Randomized, Double-Blind, Plac= ebo-Controlled, Multicenter Clinical Trial. JAMA Neurol 2022 1;77(5) 10. ClinicalTrials.gov. 2022. A Study to Test Efficacy and Safety of Rozano= lixizumab in Adult Patients With Generalized Myasthenia Gravis. https://cli= nicaltrials.gov/ct2/show/NCT03971422. Accesed October 2022=C2=A0 11. Chen J, et al. Incidence, mortality, and economic burden of myasthenia = gravis in China: A nationwide population-based study. Lancet Reg Health Wes= t Pac: 2020;5:100063. 12. National institute of Neurological Disorders and Stroke. 2022. Myasthen= ia Gravis Fact Sheet. https://www.ninds.nih.gov/myasthenia-gravis-fact-shee= t. Accessed October 2022. 13. Dong D, et al. Gender differences in quality of life among patients wit= h myasthenia gravis in China. Health and Quality of Life Outcomes 2020 18;2= 96 14. Myasthenia Gravis Foundation of America. MG Quick Facts. https://myasth= enia.org/MG-Education/MG-Quick-Facts Accessed October 2022 15. Smith B, et al. Generation and characterization of a high affinity anti= -human FcRn antibody, rozanolixizumab, and the effects of different molecul= ar formats on the reduction of plasma IgG concentration. MAbs. 2018;10:1111= -30. 16. Kiessling P, et al. The FcRn inhibitor rozanolixizumab reduces human se= rum IgG concentration: A randomized phase 1 study. Sci Transl Med. 2017;9(4= 14:eaan1208). 17. US Food and Drug Administration https://www.accessdata.fda.gov/scripts/= opdlisting/oopd/detailedIndex.cfm?cfgridkey=3D669918. Accessed August 2022 18. European Medicines Agency, EU/3/20/2272: Orphan designation for the tre= atment of myasthenia gravis https://www.ema.europa.eu/en/medicines/human/or= phan-designations/eu3202272. Accessed August 2022=C2=A0 GenericFile Zilucoplan FDA EMA Regulatory Filing Press Release FINAL 14 Nov 2022 For Is= sue (https://mb.cision.com/Public/18595/3666193/811eb96fd5f8797a.pdf) ______________________ If you would rather not receive future communications from UCB SA, please g= o to https://eu.vocuspr.com/OptOut.aspx?2973226x20421x121568x1x6868579x2400= 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) UCB Media Room: U.S. FDA acceptance of new drug application and EMA MAA validation for zilucoplan for the treatment of generalized myasthenia gravis in adult patients

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