UCB (EBR:UCB) UCB Media Room: rozanolixizumab BLA for the treatment of generalized myasthenia gravis filed with U.S. FDA and designated for Priority Review

Directive transparence : information réglementée

06/01/2023 07:00
https://mb.cision.com/Public/18595/3693925/86e384ee3a575ab3_800x800ar.png ** UCB announces rozanolixizumab BLA for the treatment of generalized myast= henia gravis filed with U.S. FDA and designated for Priority Review ------------------------------------------------------------ =C2=B7 Biologic License Application (BLA) designated Priority Review by FDA= and seeks approval for rozanolixizumab for the treatment of adults with ge= neralized myasthenia gravis (gMG) who are anti-acetycholine receptor (AChR)= or anti-muscle-specific tyrosine kinase (MuSK) antibody positive=C2=A0 =C2=B7 Rozanolixizumab FDA Priority Review follows recent European Medicine= s Agency (EMA) validation of the Marketing Authorization Application (MAA) = for rozanolixizumab in adults with gMG=C2=A0 =C2=B7 FDA and EMA submissions based on pivotal Phase 3 MycarinG study in g= MG which demonstrated treatment with rozanolixizumab resulted in clinically= meaningful and statistically significant improvements in MG specific outco= mes =C2=B7 UCB expects to receive feedback from the agencies in Q2 of 2023=C2= =A0 Brussels (Belgium) 6 Jan 2023 =E2=80=93 7:00AM (CET) =E2=80=93 UCB, a globa= l biopharmaceutical company, today announced that the U.S. Food and Drug Ad= ministration (FDA) has accepted the company=E2=80=99s filing to review a Bi= ologic License Application (BLA) for its investigational treatment rozanoli= xizumab, and that the Agency has granted Priority Review.^1 Rozanolixizumab= is a subcutaneous (SC) monoclonal antibody targeting the neonatal Fc recep= tor (FcRn) for the treatment of adults with generalized myasthenia gravis (= gMG) who are anti-acetycholine receptor (AChR) or anti-muscle-specific tyro= sine kinase (MuSK) antibody positive^2.=C2=A0 A FDA Priority Review designation is typically granted by the Agency to a m= edicine which, if approved, could deliver significant improvements in the s= afety or effectiveness of the treatment, diagnosis, or prevention of seriou= s conditions when compared to standard applications3. Priority Review desig= nation means the FDA=E2=80=99s goal is to take action on an application wit= hin 6 months, compared to 10 months under standard review^3. In 2019, the U= .S. FDA granted orphan drug designation to rozanolixizumab for the treatmen= t of MG.^4 The safety and efficacy of rozanolixizumab have not been established and th= ey are not currently approved for use in any indication by any regulatory a= uthority worldwide. =C2=A0=C2=A0 The FDA Priority Review designation follows the recent European Medicines A= gency (EMA) validation of the Marketing Authorization Application (MAA) for= rozanolixizumab for the treatment of adults with AChR or MuSK antibody pos= itive gMG who require treatment in addition to steroids or non-steroidal im= munosuppressants. Validation confirms that the application is complete and = the formal review process by the EMA=E2=80=99s Committee for Medicinal Prod= ucts for Human Use (CHMP) can begin. Orphan designation was granted by the = European Commission in April 2020 to rozanolixizumab for the treatment of m= yasthenia gravis.^5 UCB expects to receive feedback from both the FDA and EMA during the second= quarter of 2023.=C2=A0 =E2=80=9CPeople living with MG suffer from unpredictable, fluctuating, and = debilitating symptoms that have a huge impact on their lives, and there is = a clear need for additional targeted treatments. We are firmly committed to= supporting the gMG community by providing solutions to help improve outcom= es for patients and reduce the day-to-day burden of the disease,=E2=80=9D s= aid Charl van Zyl, =C2=A0Executive Vice President Neurology Solutions & Hea= d of EU/International Markets, UCB. =E2=80=9CThe FDA=E2=80=99s decision to = assess rozanolixizumab via their priority review process, as well as the re= cent filing of the MAA in Europe, brings us important steps further on our = journey towards approvals for rozanolixizumab. We look forward to working w= ith the FDA and EMA to help bring this new treatment option to patients.=E2= =80=9D 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.^6 People living with gMG can experience a variety of sympto= ms, 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.^4,7=C2=A0In the U= .S. the prevalence of MG is estimated at 14 to 20 per 100,000 population; a= pproximately 36,000 to 60,000 cases.^4 In Europe, the prevalence is estimat= ed at 10 per 100,000 population.^8=C2=A0 Data from the MycarinG study The Priority Review BLA and the MAA are based on data from the pivotal Phas= e 3 MycarinG study (NCT03971422), in which rozanolixizumab demonstrated sta= tistically significant and clinically meaningful improvements in MG-specifi= c outcomes in patients with AChR MuSK antibody positive MG. In the primary = endpoint, rozanolixizumab significantly reduced MG-ADL from baseline to Day= 43. Rozanolixizumab showed an LS mean difference vs placebo (95% CI) of -2= .59 points at the 7mg/kg dose and -2.62 points at the 10mg/kg dose.^9 Furthermore, a greater percentage of patients in the rozanolixizumab 7mg/kg= and 10mg/kg arms than the placebo arm achieved a 2.0-point or greater impr= ovement (p=EF=80=BC0.001) in MG-ADL, a 3.0-point or greater improvement in = Quantitative Myasthenia Gravis (QMG) scores and a 3.0-point or greater impr= ovement in Myasthenia Gravis Composite (MGC) scores^7, demonstrating clinic= ally meaningful reductions in these assessments. Rozanolixizumab demonstrated an acceptable safety and tolerability profile = with similar occurrences of TEAEs between both doses. A higher proportion o= f TEAEs occurred in the active treatment arms versus placebo (81.3% for 7 m= g/kg, 82.6% for 10 mg/kg and 67.2% for placebo) and were comparable between= the rozanolixizumab groups. The most frequently reported TEAEs were headac= he, diarrhea, pyrexia, and nausea. A higher incidence of headache was repor= ted in the rozanolixizumab groups versus placebo, with most cases mild to m= oderate and severe cases generally managed with non-opioid analgesics.Treat= ment discontinuation rates due to TEAEs were low.^7 In the MycarinG study, 200 patients were randomised 1:1:1 to receive weekly= rozanolixizumab 7 mg/kg (N=3D66), 10 mg/kg (N=3D67) or placebo (N=3D67) fo= r 6 weeks, which was followed by an 8-week observation period.^6 =E2=80=9CPatients living with MG may experience high disease and treatment = burden resulting in a significant impact on their daily lives. If approved,= rozanolixizumab has the potential to address unmet needs of gMG patients,= =E2=80=9D said Iris Loew-Friedrich, Executive Vice-President and Chief Medi= cal Officer at UCB. =E2=80=9CThrough rozanolixizumab and zilucoplan, we int= end to bring two medicines with different mechanisms of action that have th= e potential to provide targeted treatment options to patients. With our gMG= pipeline, we hope to address both drivers of disease pathology and which a= ccount for approximately 95% of people living with gMG. Priority Review Des= ignation by the FDA for rozanolixizumab reflects the extent to which our sc= ience speaks for itself in potentially addressing the significant unmet nee= ds still faced by the gMG community.=E2=80=9D UCB is currently investigating two potential therapies with different modes= of action for the treatment of gMG. Alongside rozanolixizumab, a NDA for z= ilucoplan =E2=80=93 a subcutaneous self-administered peptide inhibitor of c= omplement component 5 (C5 inhibitor) has recently been filed with the U.S. = FDA for the treatment of adults with AChR antibody positive gMG. Additional= ly, zilucoplan received MAA validation from the EMA for the treatment of ad= ults with AChR antibody positive gMG and who require treatment in addition = to steroids or non-steroidal immunosuppressants.^10,11,12 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.^13 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.^4, 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.^4,14=C2=A0gMG can occur in any race, although previou= s studies have shown that women are more often impacted than men.^15,16 Mos= t patients with gMG have pathogenic IgG antibodies that disrupt the transmi= ssion of nerve impulses to muscles in the NMJ and some activate the complem= ent cascade.^1 Complement-mediated destruction via MAC formation is a key m= echanism causing damage at the NMJ and is the key driver of disease in AChR= antibody positive gMG gMG. About the rozanolixizumab MycarinG study^17=C2=A0 =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. T= he primary endpoint for the MycarinG study is change from baseline to day 4= 3 in the Myasthenia Gravis-Activities of Daily Living (MG-ADL) score, an ei= ght-item patient-reported scale developed to assess MG symptoms and their e= ffects on daily activities. Additional endpoints include response rates, ch= anges in the Myasthenia Gravis composite (MGC) score, the Quantitative MG (= QMG) score, patient-reported outcomes and adverse events (AEs). The majorit= y of patients taking part in the MycarinG study opted to enroll in the open= label extensions to this clinical trial. As a result, UCB is exploring the= potential for further extension studies into this treatment.=C2=A0 For more information about the trial, visit https://clinicaltrials.gov/ct2/= show/NCT03971422. 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.^1,18 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.^2 Orphan designation was granted in = 2020 by the European Commission for rozanolixizumab to the treatment of mya= sthenia gravis.^3 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 zilucoplan 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.^8 In 20= 19, the US FDA granted orphan drug designation to zilucoplan for the treatm= ent of myasthenia gravis.^9 Orphan designation was granted in 2022 by the E= uropean Commission to zilucoplan for the treatment of myasthenia gravis.^10 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 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 encephalitis (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 approximately 8,600 peopl= e in approximately 40 countries, the company generated revenue of =E2=82=AC= 5.8 billion in 2021. UCB is listed on Euronext Brussels (symbol: UCB). 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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.=C2=A0 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.=C2=A0 References: 1. Data on file. 2. Smith B, et al. Generation and characterization of a high affinity anti-= human FcRn antibody, rozanolixizumab, and the effects of different molecula= r formats on the reduction of plasma IgG concentration. MAbs. 2018;10:1111-= 30. 3. US Food and Drug Administration, https://www.fda.gov/patients/fast-track= -breakthrough-therapy-accelerated-approval-priority-review/priority-review,= Accessed January 2023 4. US Food and Drug Administration https://www.accessdata.fda.gov/scripts/o= pdlisting/oopd/detailedIndex.cfm?cfgridkey=3D669918 Accessed January 2023 5. European Medicines Agency, EU/3/20/2272: Orphan designation for the trea= tment of myasthenia gravis https://www.ema.europa.eu/en/medicines/human/orp= han-designations/eu3202272 Accessed January 2023 6. Myasthenia Gravis Foundation of America. Clinical Overview of MG. https:= //myasthenia.org/Professionals/Clinical-Overview-of-MG. Accessed January 20= 23 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. 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 January 2023. 9. Bril V, et al. Rozanolixizumab in generalized myasthenia gravis: Respond= er analyses from the Phase 3 MycarinG study. Poster 204, AANEM 2022. 10. Howard J, et al. Clinical Effects of the Self-administered Subcutaneous= Complement Inhibitor Zilucoplan in Patients With Moderate to Severe Genera= lized Myasthenia Gravis: Results of a Phase 2 Randomized, Double-Blind, Pla= cebo-Controlled, Multicenter Clinical Trial. JAMA Neurol 2022 1;77(5) 11. US Food and Drug Administration https://www.accessdata.fda.gov/scripts/= opdlisting/oopd/detailedIndex.cfm?cfgridkey=3D699319. Accessed January 2023 12. Data on file. 13. 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. 14. National institute of Neurological Disorders and Stroke. 2022. Myasthen= ia Gravis Fact Sheet. https://www.ninds.nih.gov/myasthenia-gravis-fact-shee= t. Accessed January 2023. 15. 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 16. Myasthenia Gravis Foundation of America. MG Quick Facts. https://myasth= enia.org/MG-Education/MG-Quick-Facts Accessed January 2023 17. ClinicalTrials.gov =E2=80=98A Study to Test Efficacy and Safety of Roza= nolixizumab in Adult Patients With Generalized Myasthenia Gravis=E2=80=99: = =C2=A0https://clinicaltrials.gov/ct2/show/NCT03971422. Accessed January 202= 3. 18. 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). GenericFile UCB FDA BLA Rozanolixizumab Press Release 06 January ENG (https://mb.cision= .com/Public/18595/3693925/83418e0d34a70dd2.pdf) ______________________ If you would rather not receive future communications from UCB SA, please g= o to https://eu.vocuspr.com/OptOut.aspx?2973226x20421x125555x1x6868579x2400= 0x6&Email=3Dregnews%40symexglobal.com. UCB SA, All=C3=A9e de la Recherche, 60 ., Brussels, . B - 1070 Belgium