American Association of Sensory Electrodiagnostic Medicine

Results presented across UCB's generalized myasthenia gravis (gMG) development program builds the body of evidence around the complexities of gMG Presentations to include data from the Phase 3 MycarinG study of rozanolixizumab as well as the Phase 3 RAISE and RAISE-XT studies of zilucoplan BRUSSELS, Belgium, Sept. 22, 2022 /PRNewswire/ -- UCB, a global biopharmaceutical company, announced today it is presenting results from across its portfolio in generalized myasthenia gravis (gMG) at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) annual meeting featuring the Myasthenia Gravis Foundation of America (MGFA) Scientific Session, September 21 – 24. Presentations include study results for its investigational treatments, zilucoplan, a self-administered, subcutaneous (SC) peptide inhibitor of complement component 5 (C5 inhibitor) and rozanolixizumab, an SC-infused monoclonal antibody targeting the neonatal Fc receptor (FcRn), in adults with gMG. In addition, the company is also presenting real-world findings into the burden of the disease for society and the potential role of a digital application in improving care. The safety and efficacy of rozanolixizumab and zilucoplan have not been established and neither treatment is approved for use in any indication by any regulatory authority worldwide. "Patients living with gMG experience high disease and treatment burden resulting in a significant impact on their daily lives. The data being presented at AANEM and the MG Scientific Session reinforce the potential of UCB's two investigational medicines with different mechanisms of action to provide targeted treatment options to patients," said Iris Loew-Friedrich, Executive Vice President and Chief Medical Officer at UCB. "We are committed to meeting patients' needs, regardless of antibody profile, including those with MuSK Ab+ gMG who have particularly limited treatment options. With our gMG pipeline, we hope to address both drivers of disease pathology and which account for approximately 95% of patients living with gMG." Rozanolixizumab MycarinG Phase 3 Results A subgroup analysis presented from the Phase 3 MycarinG study (Poster 16, MGFA Scientific Session) 1 analyzes the efficacy of rozanolixizumab in patients with muscle specific kinase antibody-positive (MuSK-Ab+) gMG, which is often more severe and harder to treat than acetylcholine receptor antibody positive (AChR-Ab+) gMG.2 In the analysis, rozanolixizumab demonstrated statistically significant and clinically meaningful improvements in MG-specific outcomes in patients with MuSK-Ab+ gMG, that were consistent with results in AChR-Ab+ gMG and the overall population. Improvements in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score for the overall population (n=200), including MuSK-Ab+ patients, were -3.37 for 7mg/kg (n=66; 5 MuSK Ab+) and -3.40 for 10mg/kg (n=67) vs -0.78 (n=67) for placebo. In the MuSK-Ab+ specific subgroup, improvement in MG-ADL was –7.28 (7mg/kg; n=5), –4.16 (10mg/kg; n=8), and 2.28 (placebo; n=8). In the AChR-Ab+ specific subgroup, improvement in MG-ADL was –3.03 (7mg/kg; n=60), –3.36, (10mg/kg; n=60), and –1.10 (placebo; n=59).1 In a responder analysis from MycarinG (Poster 204, AANEM)3, results presented demonstrated that rozanolixizumab significantly reduced MG-ADL from baseline to Day 43. In this primary endpoint, rozanolixizumab showed an LS mean difference vs placebo of 2.59 points at the 7mg/kg dose and 2.62 points at the 10mg/kg dose. 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 improvement in MG-ADL, a 3.0-point or greater improvement in Quantitative Myasthenia Gravis (QMG) scores and a 3.0-point or greater improvement in Myasthenia Gravis Composite (MGC) scores. Rozanolixizumab had an acceptable safety profile and was generally well tolerated with similar occurrences of TEAEs between both doses.3 A further safety analysis of the MycarinG trial (Oral presentation, 'Clinical Trials 2' session, MGFA Scientific Session),4 showed that rozanolixizumab was generally well tolerated, with the majority of treatment emergent adverse events (TEAEs) being mild to moderate in severity. A higher proportion of TEAEs occurred in the active treatment arms versus placebo (81.3% for 7 mg/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 headache, diarrhea, pyrexia and nausea. A higher incidence of headache was reported in the rozanolixizumab groups versus placebo, with most cases mild to moderate and severe cases generally managed with non-opioid analgesics. There were no severe or serious infections in the rozanolixizumab groups. Treatment withdrawal due to TEAEs was low; the rate was similar in the rozanolixizumab 7 mg/kg and placebo groups and higher in the rozanolixizumab 10 mg/kg group.4 Zilucoplan Phase 3 RAISE and RAISE-XT Results An interim analysis from RAISE-XT (data cut off 18 February 2022), a Phase 3, multicenter, open-label extension study (Poster 14, MGFA Scientific Session) is also being presented.5 This ongoing study recruited patients with AChR-Ab+ gMG who participated in randomized Phase 2 (NCT03315130) and Phase 3 (NCT04115293) zilucoplan studies. Building on the data seen in the double-blind Phase 2 and Phase 3 studies, results demonstrated a favorable long-term safety profile for zilucoplan over 24 weeks with no major safety findings, with efficacy in patients who had previously received zilucoplan continuing to improve, and efficacy demonstrated as early as week 1 in patients who switched from placebo. At extension study Week 12, after 24 weeks, the zilucoplan group achieved an LS mean improvement in MG-ADL score from the double-blind study baseline of −6.30. MG-ADL improvement for the placebo-switch group, after 12 weeks of zilucoplan, was −6.32. A presentation on the quality-of-life (QoL) outcomes with zilucoplan from the Phase 3 RAISE study (NCT04115293) (Oral presentation, 'Clinical Trials 2' session, MGFA Scientific Session)6 demonstrated that zilucoplan clinically meaningfully and highly statistically significantly improved MG-ADL at week 12 (LS mean difference v placebo –2.09; p<0.001) and showed consistently greater improvement in fatigue vs placebo (LS mean difference vs placebo at Week 12, –3.06; nominal p=0.0069). An overall Work Impairment due to problem score with zilucoplan vs placebo (LS mean difference vs placebo –12.83; p=0.0912) was also observed. Zilucoplan demonstrated a favorable safety profile, with a similar rate of TEAEs between zilucoplan (76.7%) and placebo (70.5%), and good tolerability. The most common TEAEs were injection-site reactions (26.7% zilucoplan vs 14.8% placebo); all were non-serious, and mild in severity, except for one instance of injection-site pain of moderate severity in the zilucoplan group and no patients discontinued due to an injection-site reaction. All patients in the zilucoplan arm who completed the 12-week treatment period have entered the ongoing RAISE-XT extension study (NCT04225871). Additionally, in a detailed responder analysis from Phase 3 RAISE trial being presented (Poster 200, AANEM)7 significantly higher proportions of patients receiving zilucoplan achieved ³3-point and ³5-point improvements in MG-ADL and QMG without rescue therapy vs placebo, respectively Zilucoplan demonstrated a clinically meaningful placebo-corrected mean improvement of 2.09 points (p<0.001) in MG-ADL, with 73.1% (p<0.001) of patients receiving zilucoplan achieving a 3.0-point or greater reduction in MG-ADL compared to placebo (46.1%) and 58% (p=0.0012) of patients receiving zilucoplan achieving a 5.0-point or greater reduction in QMG compared to placebo (33.3%). Zilucoplan had a favorable safety profile with no major safety findings and good tolerability.7 Real-world costs of gMG and digital application supporting patients Data from a study exploring the health care utilization and societal costs of MG in Norway (Poster 9, MGFA Scientific Session)8 highlighted the burden on both patients and society. It showed that societal costs such as lost life years, QoL, and productivity are significant and greater than direct treatment-related costs (estimated to be only 11.5% of societal costs). A further study on the real-world assessment of patient perceptions on an MG symptom-tracking application9 showed the potential of the smartphone application to equip patients with information that would allow them to better communicate their individual disease experience to their healthcare professional while also making behavioral changes to better manage their disease. Further assessment of this application is underway. (Oral presentation, 'Outcomes' session, MGFA Scientific Session). "We are proudly and firmly committed to supporting the gMG community by increasing knowledge and understanding of the true burden of this disease to help improve outcomes," said Charl van Zyl, Executive Vice President Neurology & Head of Europe/International Markets at UCB. "By focusing on patients and reinforcing our gMG pipeline with a platform of support services and digital innovations, we aim to transform the lives of people living with this disease." UCB anticipates filing regulatory submissions in the European Union, Japan and the U.S. for both zilucoplan and rozanolixizumab later this year. For further information, contact UCB: Brand Communications, Rare Diseases Jim Baxter T+32.2.473.78.85.01 [email protected] U.S. Communications, Rare Diseases Daphne Teo T +1.770.880.7655 [email protected] Corporate Communications, Media Relations Laurent Schots T+32.2.559.92.64 [email protected] Investor Relations Antje Witte T +32.2.559.94.14 [email protected] About Generalized Myasthenia Gravis (gMG) Myasthenia gravis is a rare disease impacting almost 200,000 patients in the U.S., EU and Japan.10,11 People living with gMG can experience a variety of symptoms, including drooping eyelids, double vision and difficulty swallowing, chewing and talking, as well as severe muscular weakness that can result in life threatening weakness of the muscles of respiration.12 gMG is a chronic and unpredictable auto-immune disease in which pathogenic autoantibodies can inhibit synaptic transmission at the neuro-muscular junction 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.13 gMG can occur at any age and in any race, although previous studies have shown that women are more often impacted than men.12 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. Complement-mediated destruction via MAC formation is a key mechanism causing damage at the NMJ and is the key driver of disease in AChR Ab+ gMG. About the zilucoplan RAISE study 14 The RAISE study (NCT04115293) is a multi-center, Phase 3, randomized, double-blind, placebo-controlled study to confirm the efficacy, safety, and tolerability of zilucoplan in patients with gMG. Patients were randomized in a 1:1 ratio to receive daily subcutaneous (SC) doses of 0.3 mg/kg zilucoplan 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. 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) score from baseline to Week 12, time to rescue therapy, the proportion with minimal symptom expression (MSE) (defined as MG-ADL of 0 or 1), the proportion with a ≥3-point reduction in MG-ADL and the proportion with a ≥5-point reduction in QMG, all measured at Week 12. Secondary safety endpoint is incidence of TEAEs. Patients who completed the RAISE trial had the possibility to enter the open label extension study, RAISE-XT (NCT04225871). For more information about the trial visit . About the rozanolixizumab MycarinG study 15 The MycarinG study (NCT03971422) is a multi-center, Phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of rozanolixizumab in adult patients with gMG, with an open-label extension. The primary endpoint for the MycarinG study is change in the Myasthenia Gravis-Activities of Daily Living (MG-ADL) score, an eight-item patient-reported scale developed to assess MG symptoms and their effects on daily activities. Additional endpoints include response rates, changes in the Myasthenia Gravis composite (MGC) score, the Quantitative MG (QMG) score, patient-reported outcomes and adverse events (AEs). The majority 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. For more information about the trial, visit . About Zilucoplan Zilucoplan is a once-daily self-administered SC peptide inhibitor of complement component 5 (C5 inhibitor) under clinical development by UCB in gMG. Results from the RAISE study, a multi-center, Phase 3, randomized, double-blind, placebo-controlled study demonstrated the efficacy, safety, and tolerability of zilucoplan in patients with gMG, and regulatory submissions are planned in 2022. In 2019, the US FDA granted orphan drug designation to zilucoplan for the treatment of myasthenia gravis.16 Orphan designation was granted in 2022 by the European Commission to zilucoplan for the treatment of myasthenia gravis.17 The safety and efficacy of zilucoplan have not been established and it is not currently approved for use in any indication by any regulatory authority worldwide. About Rozanolixizumab Rozanolixizumab is an SC administered, humanized monoclonal antibody that specifically 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 concentration of pathogenic IgG autoantibodies.18,19 Rozanolixizumab is under clinical development with the aim of improving the lives of people with pathogenic IgG-autoantibody-driven autoimmune diseases. In 2019, the US FDA granted orphan drug designation to rozanolixizumab for the treatment of myasthenia gravis.20 Orphan designation was granted in 202021 by the European Commission for rozanolixizumab for 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 worldwide. About UCB in Rare Diseases At UCB, we don't just see patients or population sizes, we see people in need. Through decades of serving the neurology and immunology communities, we have improved lives with impactful medicines and by enhancing the social and emotional well-being of patients. As a continuation of our heritage, we are now expanding our efforts to tackle rare neurological and immunological diseases where current options offer little hope, including investigational treatments for gMG, MOG-AD and AIE. About UCB UCB, Brussels, Belgium () 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 more than 7,600 people in approximately 40 countries, UCB generated revenue of €5.3 billion in 2020. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCB_news Forward looking statements This press release may contain 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 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, will progress to product approval 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 differences 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 it does not reflect any potential impact from the evolving COVID-19 pandemic, unless indicated otherwise. UCB is following the worldwide developments diligently to assess the financial significance of this pandemic to UCB. UCB 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. 1 Habib AA, et al. Efficacy of rozanolixizumab in muscle-specific kinase antibody-positive generalized myasthenia gravis: Outcomes from the randomized, Phase 3 MycarinG study. Poster 16, MGFA Scientific Session, AANEM 2022. 2 Rodolico C, et al. MuSK-Associated Myasthenia Gravis: Clinical Features and Management. Front Neurol. 2020;11:660 3 Bril V, et al. Rozanolixizumab in generalized myasthenia gravis: Responder analyses from the Phase 3 MycarinG study. Poster 204, AANEM 2022. 4 Vu T, et al. Safety and tolerability of rozanolixizumab in the randomized Phase 3 MycarinG study. Oral presentation, MGFA Scientific Session at AANEM 2022. 5 Genge A, et al. Safety and tolerability of zilucoplan in RAISE-XT: A multicenter, open-label extension study in patients with generalized myasthenia gravis. Poster 14, MGFA Scientific Session, AANEM 2022. 6 Weiss MD, et al, Quality of life outcomes in RAISE: A double-blind randomized, placebo-controlled study of zilucoplan in gMG. Oral presentation. MGFA Scientific Session, AANEM 2022. 7 Vu T, et al. Efficacy and safety of zilucoplan in myasthenia gravis: Responder analysis from the randomized Phase 3 RAISE trial. Poster 200, AANEM 2022. 8 Bugge C, et al. Burden of myasthenia gravis: Health care utilization and societal costs in Norway. Poster 9, MGFA Scientific Session, AANEM 2022. 9 Steels J-C, et al. Improving outcomes by tracking symptoms, triggers and quality of life. Real-world assessment and patient perceptions of a prototype myasthenia gravis tracking app. Oral presentation. MGFA Scientific Session, AANEM 2022. 10 Chen J, et al. Incidence, mortality, and economic burden of myasthenia gravis in China: A nationwide population-based study. Lancet Reg Health West Pac. 2020;5:100063. 11 Gilhus N. Myasthenia Gravis. N Engl J Med. 2016;375:2570-2581. 12 Hansen JS, et al. Mortality in myasthenia gravis: A nationwide population-based follow-up study in Denmark. Muscle Nerve. 2016;53:73-77. 13 Myasthenia Gravis Foundation of America. Clinical Overview of MG. . Accessed August 2022. 14 ClinicalTrials.gov 'Safety, Tolerability, and Efficacy of Zilucoplan in Subjects With Generalized Myasthenia Gravis (RAISE)': . Accessed August 2022. 15 ClinicalTrials.gov 'A Study to Test Efficacy and Safety of Rozanolixizumab in Adult Patients With Generalized Myasthenia Gravis': . Accessed August 2022. 16 US Food and Drug Administration.. Accessed August 2022. 17 Data on file. 18 Kiessling P, et al. The FcRn inhibitor rozanolixizumab reduces human serum IgG concentration: A randomized phase 1 study. Sci Transl Med. 2017;9(414). 19 Smith B, et al. Generation and characterization of a high affinity anti-human FcRn antibody, rozanolixizumab, and the effects of different molecular formats on the reduction of plasma IgG concentration. MAbs.2018;10:1111-1113. 20 US Food and Drug Administration. . Accessed August 2022 21 European Medicines Agency. . Accessed August 2022 SOURCE UCB, Inc.