UCB (EBR:UCB) UCB Media Room: Efficacy and safety results for zilucoplan and rozanolixizumab in generalized myasthenia gravis

Directive transparence : information réglementée Communiqué sur comptes, résultats, chiffres d’affaires

10/05/2022 07:02
https://mb.cision.com/Public/18595/3563591/a7c4ad9e4b349b95_800x800ar.png ** UCB presents efficacy and safety results for zilucoplan and rozanolixizu= mab in generalized myasthenia gravis ------------------------------------------------------------ =C2=B7 Phase 3 RAISE and MycarinG studies in generalized myasthenia gravis = (gMG) show zilucoplan and rozanolixizumab improve gMG-specific outcomes wit= h consistent statistical significance and clinical relevance=C2=A0 =C2=B7 Regulatory submissions for zilucoplan and rozanolixizumab are planne= d for later this year =C2=B7 Findings from a real-world smartphone data collection study reaffirm= UCB=E2=80=99s commitment to delivering pioneering, tailored care solutions= for individuals living with gMG=C2=A0 Brussels (Belgium), 10 May 2022 =E2=80=93 7:00 (CEST) =E2=80=93 UCB, a glob= al biopharmaceutical company, today announced results from two Phase 3 stud= ies evaluating its investigational treatments, zilucoplan, a self-administe= red, subcutaneous (SC) peptide inhibitor of complement component 5 (C5 inhi= bitor) and rozanolixizumab, an SC-infused monoclonal antibody targeting the= neonatal Fc receptor (FcRn) in adults with generalized myasthenia gravis (= gMG).=C2=A0 These results will be presented as posters at the 14th Myasthenia Gravis Fo= undation of America (MGFA) International Conference on Myasthenia and Relat= ed Disorders, taking place from May 10-12, 2022. Phase 3 RAISE results=C2=A0=C2=A0 =C2=A0 Data from the Phase 3 RAISE trial (NCT04115293) (poster 26)^1=C2=A0demonstr= ated treatment with zilucoplan (0.3 mg/kg daily) resulted in clinically mea= ningful and statistically significant improvements in key gMG-specific outc= omes compared with placebo in patients with acetylcholine receptor autoanti= body positive (AChR+) gMG.=C2=A0 The study met its primary endpoint with zilucoplan showing a placebo-correc= ted mean improvement of 2.12 points in the Myasthenia Gravis Activities of = Daily Living (MG-ADL) score at week 12 (p<0.001). Significant improvement i= n the MG-ADL was observed from Week 1.=C2=A0 All key secondary endpoints were also met, including statistically signific= ant improvements in the Quantitative Myasthenia Gravis (QMG) score, Myasthe= nia Gravis Composite (MGC) and Myasthenia Gravis Quality of Life 15-Item re= vised (MG-QoL15r), again with significant improvement observed from Week 1.= The proportion of patients on zilucoplan who responded to treatment by at = least a 3-point reduction on MG-ADL and at least a 5-point reduction in QMG= were also significantly higher than placebo. =C2=A0 A favorable safety profile and good tolerability was observed, consistent w= ith prior data, showing a similar rate of treatment-emergent adverse events= (TEAEs) between zilucoplan (76.7%) and placebo (70.5%). The most common TE= AEs were injection site bruising, headache, diarrhea, and MG worsening. In the RAISE study, 174 patients were randomised to Placebo (N=3D88) and Zi= lucoplan 0.3 mg/kg (N=3D86). Patient demographics and baseline disease char= acteristics were generally balanced between treatment arms. =E2=80=9CThe results from the RAISE study are an exciting development in th= e gMG treatment paradigm and reinforce the critical role that complement in= hibition could play for physicians treating patients with this debilitating= illness. By targeting the underlying mechanisms of gMG at the neuromuscula= r junction, complement inhibitors like zilucoplan have the potential to pro= vide rapid, consistent disease control earlier in the disease course. These= findings are an encouraging sign that we may be able to meet patients=E2= =80=99 needs effectively, with treatments that are minimally invasive and w= ell tolerated,=E2=80=9D said James F. Howard, MD, Distinguished Professor o= f Neuromuscular Disease, Professor of Neurology, Medicine and Allied Health= , The University of North Carolina at Chapel Hill School of Medicine and le= ad investigator in the RAISE trial. Phase 3 MycarinG results Results from the Phase 3 MycarinG study (NCT03971422) (poster 25)^2 demonst= rated that rozanolixizumab significantly reduced MG-ADL from baseline to Da= y 43 at ~7 mg/kg and ~10 mg/kg doses compared with placebo in patients with= AChR or muscle-specific tyrosine kinase (MuSK) autoantibody positive gMG. = Rozanolixizumab demonstrated a placebo-corrected mean improvement of 2.586 = points at the ~7 mg/kg dose and 2.619 points in the MG-ADL at the ~10 mg/kg= dose compared with placebo (both doses at p<0.001).=C2=A0 Rozanolixizumab treatment reduced mean maximum total IgG levels by more tha= n 70% (71 % for 7 mg/kg and 78% for 10 mg/kg) and anti-AChR autoantibody le= vels decreased over the treatment period in line with the total IgG reducti= on. Rozanolixizumab was generally well tolerated, with the majority of TEAE= s being mild to moderate in intensity. A higher proportion of TEAEs occurre= d in the active treatment arms versus placebo (81.3% for ~7 mg/kg, 82.6% fo= r ~10 mg/kg and 67.2% for placebo). The most frequently reported TEAE was h= eadache, most of which were mild to moderate, with severe headaches managed= with over-the-counter analgesic medications. The other most common TEAEs w= ere diarrhea, pyrexia and nausea. Due to the fluctuating and unpredictable nature of gMG and the subjectivity= of symptoms, patient reported outcomes (PROs) help provide greater insight= into disease impact and more granular detail on the effect of treatments t= han traditional endpoints. Within the MycarinG study, the MG Symptoms PRO m= easure, which was developed by UCB with patients, was used to assess a seri= es of quality-of-life measures, including muscle weakness fatigability, phy= sical fatigue and bulbar muscle weakness, throughout the treatment and obse= rvation periods (poster 64)^3. All three MG Symptoms PRO scales or subdomai= ns showed significant improvement from baseline with rozanolixizumab ~7 mg/= kg and ~10 mg/kg doses compared with placebo at Day 43, indicating treatmen= t with rozanolixizumab improves patients=E2=80=99 symptoms and their abilit= y to undertake daily activities. Further evaluation of the MG Symptoms PRO = measure is ongoing. In the MycarinG study, a total of 66 patients were randomized to rozanolixi= zumab 7 mg/kg, 67 to rozanolixizumab 10 mg/kg and 67 to placebo. Baseline c= haracteristics were generally balanced between treatment groups. =E2=80=9CThe one constant in gMG is unpredictability. People living with th= is disease experience symptoms that are nebulous, fluctuating, and which va= ry from one day to the next. For this reason, there is an urgent need for m= ore effective, targeted, and convenient treatments that reduce the burden o= f disease on patients=E2=80=99 daily lives. The results from the MycarinG s= tudy are extremely encouraging, and demonstrate the potential of rozanolixi= zumab as a new, effective and flexible treatment option to help ease the da= y-to-day burden of this challenging disease and improve treatment outcomes = for patients,=E2=80=9D said Professor Vera Bril, Professor of Medicine (Neu= rology), University of Toronto, Director of the Neuromuscular Section, Divi= sion of Neurology, University of Toronto and University Health Network, Tor= onto, and lead investigator of the MycarinG study. =E2=80=9CEvery person living with gMG is unique, so a one-size-fits-all tre= atment approach will never be appropriate. This is why at UCB we are invest= igating two medicines with different MOAs. This unique approach means we ma= y be able to offer physicians and patients a range of treatment options to = meet the individual needs of many different patients, and therefore leave n= o one behind in our ambition to improve outcomes in gMG,=E2=80=9D said Iris= Loew-Friedrich, Executive Vice-President and Chief Medical Officer at UCB. UCB anticipates filing regulatory submissions for both zilucoplan and rozan= olixizumab later this year. Digital innovation for patients living with myasthenia gravis Findings from a three-month observational study carried out by UCB in colla= boration with digital health company Sharecare, to collect real-world data = from gMG patients using smartphones, were also presented at the conference = (poster 84)^4. Beyond demonstrating that decentralized, smartphone-based me= thods to collect real-world data from gMG patients are feasible and may pro= vide enhanced visibility into the burden of the disease, the study also ide= ntified unique clusters of exacerbation subtypes with specific symptom repr= esentation. This requires further validation but suggests that digital phen= otyping holds promise for furthering understanding of exacerbations. This a= nalysis forms part of UCB=E2=80=99s holistic approach to delivering differe= ntiated patient experiences, combining patient insights, pioneering researc= h and artificial intelligence to deliver tailored support for individuals l= iving with gMG.=C2=A0 =E2=80=9COur gMG pipeline is supported by a holistic and integrated platfor= m of support services and digital innovation that aims to deliver broad acc= ess to seamless and flexible services across the gMG care continuum,=E2=80= =9D continued Charl van Zyl, Executive Vice President Neurology & Head of E= urope/International Markets at UCB =E2=80=9COur ultimate goal is to transfo= rm the lives of people living with this challenging disease by putting pati= ents at the center of our world and advancing scientific solutions that mee= t their complex and varying needs.=E2=80=9D=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 almost 200,000 patients in th= e U.S., EU and Japan.^5,6=C2=A0 People living with gMG can experience a var= iety of symptoms, including drooping eyelids, double vision and difficulty = swallowing, chewing and talking, as well as severe muscular weakness that c= an result in life threatening weakness of the muscles of respiration.^7 gMG is a chronic and unpredictable auto-immune disease in which pathogenic = autoantibodies can inhibit synaptic transmission at the neuro-muscular junc= tion by targeting specific proteins on the post-synaptic membrane. This dis= rupts the ability of the nerves to stimulate the muscle and results in a we= aker contraction^8. gMG can occur at any age and in any race, although prev= ious studies have shown that women are more often impacted than men.^8 Most= patients with gMG have pathogenic IgG antibodies that disrupt the transmis= sion of nerve impulses to muscles in the NMJ and some activate the compleme= nt cascade. =C2=A0Complement-mediated destruction via MAC formation is a ke= y mechanism causing damage at the NMJ and is the key driver of disease in A= ChR Ab+ gMG. About the zilucoplan RAISE study^9 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 gMG. Patients will be randomized in= a 1:1 ratio to receive daily subcutaneous (SC) doses of zilucoplan or plac= ebo for 12 weeks. The primary endpoint for RAISE study is change from baseline to Week 12 in = the Myasthenia Gravis-Activities of Daily Living (MG-ADL) score. Secondary = endpoints include change in the Quantitative Myasthenia Gravis (QMG) score,= the Myasthenia Gravis Composite (MGC) and the Myasthenia Gravis Quality of= Life 15 revised (MG-QoL15r) from baseline to Week 12, the proportion requi= ring rescue therapy, the proportion with minimum symptom expression (MSE) (= defined as MG-ADL of 0 or 1), the proportion with a =E2=89=A53-point reduct= ion in MG-ADL and the proportion with a =E2=89=A55-point reduction in QMG, = all measured at Week 12. The majority of patients taking part in the RAISE = trial opted to enroll in any future extensions to this clinical trial. As a= result, UCB is exploring the potential for further extension studies into = this treatment. For more information about the trial visit https://clinicaltrials.gov/ct2/s= how/NCT04115293.=C2=A0 About the rozanolixizumab MycarinG study^10=C2=A0 The MycarinG study (NCT03971422) is a multi-center, Phase 3, randomized, do= uble-blind, placebo-controlled study evaluating the efficacy and safety of = rozanolixizumab in adult patients with gMG, with an open-label extension.= =C2=A0 The primary endpoint for the MycarinG study is change in the Myasthenia Gra= vis-Activities of Daily Living Profile (MG-ADL) score, an eight-item patien= t-reported scale developed to assess MG symptoms and their effects on daily= activities. Additional endpoints include response rates, changes in the My= asthenia Gravis composite (MGC) score, the Quantitative MG (QMG) score, pat= ient-reported outcomes and adverse events (AEs). The majority of patients t= aking part in the MycarinG study opted to enroll in any future extensions t= o this clinical trial. As a result, UCB is exploring the potential for furt= her extension studies into this treatment. For more information about the trial, visit https://clinicaltrials.gov/ct2/= show/NCT03971422.=C2=A0 About Zilucoplan=C2=A0 Zilucoplan is a once-daily self-administered SC peptide inhibitor of comple= ment component 5 (C5 inhibitor) under clinical development by UCB in gMG. R= esults from the RAISE study, a multi-center, Phase 3, randomized, double-bl= ind, placebo-controlled study demonstrate the efficacy, safety, and tolerab= ility of zilucoplan in patients with gMG, and regulatory submissions are pl= anned in 2022.=C2=A0 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 a SC administered, humanized monoclonal antibody that sp= ecifically 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 concentr= ation of pathogenic IgG autoantibodies.^11,12 Rozanolixizumab is under clinical development with the aim of improving the= lives of people with pathogenic IgG-autoantibody-driven autoimmune disease= s. 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. 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 8,500 people in= approximately 40 countries, UCB generated revenue of =E2=82=AC5.8 billion = in 2021. 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. 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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 registration or qualification under the securities laws of such jurisdi= ction. References 1. Outcomes from RAISE: A randomized, placebo-controlled, double-blind, Pha= se 3 trial of zilucoplan in generalized myasthenia gravis. Howard JF et al.= Data presented at MGFA International Conference 2022. Poster 26. 2. Efficacy and safety of rozanolixizumab in patients with generalized myas= thenia gravis: A randomized, multicenter, double-blind, placebo-controlled,= Phase 3 study (MycarinG). Bril V et al. Data presented at MGFA Internation= al Conference 2022. Poster 25 3. Patient-reported and quality-of-life outcomes from MycarinG, a randomize= d, placebo-controlled, double-blind, Phase 3 trial of rozanolixizumab in ge= neralized myasthenia gravis. Habib A et al. Data presented at MGFA Internat= ional Conference 2022. Poster 64 4. A decentralized, prospective, observational study to collect real-world = data from patients with myasthenia gravis using smartphones. Steyaert S et = al. Data presented at MGFA International Conference 2022. Poster 84. 5. Chen J, et al. Incidence, mortality, and economic burden of myasthenia g= ravis in China: A nationwide population-based study. Lancet Reg Health West= Pac.2020;5:10063. 6. Gilhus N. Myasthenia Gravis. N Engl J Med. 2016;375:2570-2581. 7. Hansen JS, et al. Mortality in myasthenia gravis: A nationwide populatio= n-based follow-up study in Denmark. Muscle Nerve. 2016;53:73-77. 8. Myasthenia Gravis Foundation of America. Clinical Overview of MG. https:= //myasthenia.org/Professionals/Clinical-Overview-of-MG. Accessed May 2022. 9. Clinical Trials.gov =E2=80=98Safety, Tolerability, and Efficacy of Ziluc= oplan in Subjects With Generalized Myasthenia Gravis (RAISE)=E2=80=99: http= s://clinicaltrials.gov/ct2/show/NCT04115293. Accessed May 2022. 10. Clinical Trials.gov =E2=80=98A Study to Test Efficacy and Safety of Roz= anolixizumab in Adult Patients With Generalized Myasthenia Gravis=E2=80=99:= =C2=A0https://clinicaltrials.gov/ct2/show/NCT03971422. Accessed May 2022. 11. 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). 12. 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. GenericFile 20220510 UCB MGFA Press Release ENG (https://mb.cision.com/Public/18595/356= 3591/841985e256cbc57e.pdf) ______________________ If you would rather not receive future communications from UCB SA, please g= o to https://eu.vocuspr.com/OptOut.aspx?2973226x20421x104564x1x6868579x2400= 0x6&Email=3Dregnews%40symexglobal.com. UCB SA, All=C3=A9e de la Recherche, 60 ., Brussels, . B - 1070 Belgium