AQP4

Alexion, AstraZeneca Rare Disease, will present robust clinical and real-world data from its rare neurology portfolio at the American Academy of Neurology (AAN) Annual Meeting in San Diego, CA, 5 to 9 April 2025. The company will present 21 abstracts, including three oral presentations, across neuromyelitis optica spectrum disorder (NMOSD) and generalised myasthenia gravis (gMG). Presentations will offer analyses of the CHAMPION-NMOSD and PREVENT trials as well as real-world data evaluating the long-term safety profile and efficacy of Ultomiris (ravulizumab) and Soliris (eculizumab) in NMOSD and gMG. Christophe Hotermans, Senior Vice President, Head of Global Medical Affairs, Alexion, said: “At this year’s AAN, we continue to build on our legacy of innovation for people living with rare diseases by presenting new real-world and clinical evidence that highlight the transformational impact of Ultomiris and Soliris in the long-term treatment of NMOSD and gMG. This latest data will reinforce the sustained efficacy and safety profile of Ultomiris and Soliris, as well as the benefits of long-term treatment in these patient populations, offering meaningful insights to help improve patient care and deepen disease understanding.” Continued evidence reinforcing the safety profile and efficacy of Ultomiris and Soliris Two oral presentations will provide clinical and real-world evidence supporting the sustained long-term safety profile and efficacy of Ultomiris and Soliris in adults with the most common forms of NMOSD and gMG, respectively. An interim analysis of the ongoing Phase III CHAMPION-NMOSD clinical trial will reinforce the potential for Ultomiris to prevent relapses in adults with anti-aquaporin-4 (AQP4) antibody-positive (Ab+) NMOSD. Data will demonstrate that zero patients treated with Ultomiris experienced an adjudicated relapse through a median follow-up of 170.3 weeks. In addition, most patients treated with Ultomiris were clinically stable or improved on disability measures through the longer-term follow-up highlighting the importance of preventing relapses to reduce disability decline in patients with NMOSD. Results from a presentation spotlighting the three-year analysis from postmarketing surveillance (PMS) in Japan will show that treatment with Soliris demonstrated sustained effectiveness in patients with anti-acetylcholine receptor (AChR) antibody-positive (Ab+) gMG, regardless of Myasthenia Gravis Foundation of America (MGFA) classification, which is used to assess the severity of disease. Additionally, in an encore poster presentation, results from the first interim analysis from the Ultomiris gMG PMS in Japan will show that clinical effectiveness benefits were maintained in adult patients with AChR-Ab+ gMG who switched to Ultomiris from prior Soliris treatment. Real-world data underscore benefit of C5 inhibitors in NMOSD and gMG clinical practice A poster featuring real-world evidence from a global NMOSD registry will underscore the strong clinical benefit of Ultomiris and Soliris in relapse prevention in adults with AQP4-Ab+ NMOSD. Global gMG registry findings will be shared in poster presentations, including real-world data demonstrating reduced oral corticosteroid burden in patients with AChR-Ab+ gMG receiving Soliris or Ultomiris and reduced hospitalisations, MG crises and exacerbations among patients with AChR-Ab+ gMG receiving Ultomiris. Advancing understanding and innovation for the NMOSD and gMG communities An oral presentation will share results of a study evaluating glial fibrillary acidic protein (GFAP) and Neurofilament Light Chain (NfL), biomarkers of astrocyte and neuronal injury, respectively, as potential indicators of disease activity in patients with AQP4-Ab+ NMOSD. In this analysis, high baseline GFAP and NfL levels in PREVENT and CHAMPION-NMOSD serum samples were associated with clinical characteristics related to age and ambulation. Data will show that no associations were observed between levels of these biomarkers and relapse risk or time to first adjudicated on-trial relapse. A poster presentation will showcase preliminary results from Ad Scientiam’s decentralised research study, funded by Alexion, highlighting the potential clinical value of using the app-based tool, ME&MGopenTM, to collect digital data to track the daily impact of gMG symptoms in adults with AChR-Ab+ gMG, supporting its use in patient care. Two poster presentations will feature ongoing clinical studies, including the study design for the Phase III, open-label, single-arm trial evaluating Ultomiris in paediatric patients with AChR-Ab+ gMG.Additionally, an encore poster will provide an overview of the ongoing Phase III PREVAIL trial assessing the safety profile and efficacy of gefurulimab, a novel, dual-binding nanobody, optimised for weekly subcutaneous administration, in adult patients with AChR-Ab+ gMG. Further, results from Project ASPIRE (eliminAte diSparities and Promote equIty in Rare diseasE) will highlight health disparities among persons of colour (POC) who are living with gMG, underscoring the need for nationwide action plans to reduce barriers to healthcare and support for those who are disproportionally affected. Alexion presentations during AAN 2025 Lead Author Abstract Title Presentation Details Lead Author NMOSD Lead Author Abbatemarco J, et al. Abstract Title Patient Preferences for Treatment Features in Neuromyelitis Optica Spectrum Disorder (NMOSD): Results From a Discrete Choice Experiment (DCE) Presentation Details Poster Presentation Abstract #1752 7 April 2025 5:00 – 6:00PM PST Lead Author Okuda D, et al. Abstract Title Clinical and Radiological Outcomes in People with Aquaporin-4 IgG Positive Neuromyelitis Optica Spectrum Disorder Following Ravulizumab Treatment (AMAZE) Presentation Details Poster Presentation Abstract #4569 7 April 2025 5:00 – 6:00PM PST Lead Author Osborne B, et al. Abstract Title The Total Economic Impact of Anti-Aquaporin-4 Antibody-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (NMOSD) on Patients and Caregivers in the United States Presentation Details Poster Presentation Abstract #1746 7 April 2025 5:00 – 6:00PM PST Lead Author Bennett J, et al. Abstract Title Time to vaccination after rituximab (RTX) discontinuation in patients with anti–aquaporin–4 antibody–positive (AQP4-Ab+) neuromyelitis optica spectrum disorder (NMOSD): A post-hoc analysis of the CHAMPION-NMOSD trial Presentation Details Poster Presentation Abstract #1445 9 April 2025 8:00 – 9:00AM PST Lead Author Obeidat A, et al. Abstract Title NMO SPOTLIGHT Registry: Real-World Clinical Outcomes With Eculizumab and Ravulizumab in Anti-Aquaporin-4 Antibody-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (NMOSD) Presentation Details Poster Presentation Abstract Number #1837 9 April 2025 8:00 – 9:00AM PST Lead Author Wingerchuk D, et al. Abstract Title Clinical Characteristics Associated With High Baseline Glial Fibrillary Acidic Protein (GFAP) and Neurofilament Light Chain (NfL) Levels in Patients With Anti-Aquaporin-4 Antibody-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (NMOSD) From the PREVENT and CHAMPION-NMOSD Trials Presentation Details Oral Presentation Abstract #1840 9 April 2025 1:36PM PST Lead Author Pittock S, et al. Abstract Title Efficacy and Safety of Ravulizumab in Adults With Anti-Aquaporin-4 Antibody-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (NMOSD): Interim Analysis From the Ongoing Phase 3 CHAMPION-NMOSD Trial Presentation Details Oral Presentation Abstract #1733 9 April 2025 1:24PM PST Lead Author gMG Lead Author Narayanaswami P, et al. Abstract Title Effectiveness and Safety of Ravulizumab in Generalized Myasthenia Gravis (gMG): Updated Analysis From a Global Registry Presentation Details Poster Presentation Abstract #1829 5 April 2025 11:45AM – 12:45PM PST Lead Author Tandan R, et al. Abstract Title Assessment of Hospitalizations in Patients With Generalized Myasthenia Gravis (gMG) Before and During Treatment With Ravulizumab: Results From A Global Registry Presentation Details Poster Presentation Abstract #1832 5 April 2025 11:45AM – 12:45PM PST Lead Author Scheiner C, et al. Abstract Title Outcomes for Patients With Generalized Myasthenia Gravis Prescribed Ravulizumab or Efgartigimod Treatment: A Retrospective Medical Record Analysis Presentation Details Poster Presentation Abstract #1820 5 April 2025 11:45AM – 12:45PM PST Lead Author Govindarajan R Abstract Title Real-World Treatment Outcomes in Patients with Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis Who Transitioned from Efgartigimod to Ravulizumab Presentation Details Poster Presentation Abstract #4766 6 April 2025 5:00 – 6:00PM PST Lead Author Bhattacharyya S, et al. Abstract Title Characteristics of Cohort with Generalized Myasthenia Gravis in PREDICT Study Presentation Details Poster Presentation Abstract #5026 7 April 2025 11:45AM – 12:45PM PST Lead Author Niebler G, et al. Abstract Title A Phase 3, Open-Label, Single-Arm, Multicenter Study to Evaluate Ravulizumab Administered Intravenously in Pediatric Patients With Acetylcholine Receptor Antibody-Positive (AChR-Ab+) Generalized Myasthenia Gravis (gMG) Presentation Details Poster Presentation Abstract #1814 7 April 2025 5:00 – 6:00PM PST Lead Author Watanabe M, et al. Abstract Title Ravulizumab in Patients With Generalized Myasthenia Gravis (gMG) From Japan: Real-World Outcomes (Encore) Presentation Details Poster Presentation Abstract #1808 7 April 2025 5:00 – 6:00PM PST Lead Author Nowak R, et al. Abstract Title Change in concomitant immunosuppressive therapies for generalized myasthenia gravis in patients receiving complement C5 inhibitor therapies: a retrospective analysis of registry data (Encore) Presentation Details Poster Presentation Abstract #1838 7 April 2025 5:00 – 6:00PM PST Lead Author Howard J, et al. Abstract Title The phase 3 PREVAIL study assessing the efficacy and safety of subcutaneous gefurulimab in adults with generalized myasthenia gravis: trial in progress (Encore) Presentation Details Poster Presentation Abstract #1816 7 April 2025 5:00 – 6:00PM PST Lead Author Barnett-Tapia C, et al. Abstract Title Tracking Daily Impact of Generalized Myasthenia Gravis Using Smartphone-Based Digital Biomarkers: Lessons Learned from a 1-Year Study with ME&MGopenTM* Presentation Details Poster Presentation Abstract #3616 8 April 2025 11:45AM – 12:45PM PST Lead Author Gwathmey K, et al. Abstract Title Evaluation of the indirect and nonmedical impacts of generalized myasthenia gravis on patients and caregivers Presentation Details Poster Presentation Abstract #1800 8 April 2025 11:45AM – 12:45PM PST Lead Author Murai H, et al. Abstract Title Long-term Effectiveness and Safety of Eculizumab in Patients With Generalized Myasthenia Gravis (gMG): Real-World Data from Japan Presentation Details Oral Presentation Abstract #1835 9 April 2025 2:00 PM PST Lead Author Jiang N, et al. Abstract Title The path to diagnosis and treatment among patients with generalized myasthenia gravis (gMG): health disparities among persons of color from project ASPIRE (eliminAte diSparities and Promote equIty in Rare diseasE) Presentation Details Poster Presentation Abstract #1828 9 April 2025 11:45AM – 12:45PM PST Lead Author Across TAs Lead Author Yu J, et al. Abstract Title The REthinking MeAsures of DivErsity (REMADE) Study: Developing New Diversity Measures to Ensure Fair Representation in Clinical Trials (Encore) Presentation Details Poster Presentation Abstract #99 5 April 2025 11:45AM – 12:45PM PST *Ad Scientiam research study supported by Alexion Notes Alexion Alexion, AstraZeneca Rare Disease is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and delivery of life-changing medicines. A pioneering leader in rare disease for more than three decades, Alexion was the first to translate the complex biology of the complement system into transformative medicines, and today it continues to build a diversified pipeline across disease areas with significant unmet need, using an array of innovative modalities. As part of AstraZeneca, Alexion is continually expanding its global geographic footprint to serve more rare disease patients around the world. It is headquartered in Boston, US. AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Social Media @AstraZeneca. Contacts For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here. Corporate and financial

Alexion is exploring the potential of Voydeya as a monotherapy. Credit: Sai Thaw Kyar/Shutterstock.com. Alexion, AstraZeneca Rare Disease has received approval from the US Food and Drug Administration (FDA) for Voydeya (danicopan) as an add-on therapy to treat extravascular haemolysis (EVH) in adults with paroxysmal nocturnal haemoglobinuria (PNH). A first-in-class, oral Factor D inhibitor, Voydeya has been developed for patients who continue to suffer from EVH despite treatment with C5 inhibitors such as Ultomiris (ravulizumab) or Soliris (eculizumab). The FDA’s decision is grounded in the positive outcomes of the ALPHA Phase III trial, which demonstrated that Voydeya met its primary endpoint of haemoglobin change from baseline to week 12, alongside all key secondary endpoints. The drug was generally well-tolerated with no new safety concerns. As part of the ALPHA double-blind, placebo-controlled, multiple-dose trial, patients were enrolled and randomised to receive Voydeya or placebo apart from their ongoing Soliris or Ultomiris therapy over 12 weeks. See Also: US FDA grants fast track status to LISCure’s LB-P8 drug for PSC FDA extends review period for Applied Therapeutics’ govorestat NDA It aimed to assess the superiority of Voydeya as an adjunct to C5 inhibitor therapy. The trial included a prespecified interim analysis and an option for a two-year extension period for those completing the initial 24 weeks. Japan already approved Voydeya and the European Union is poised to follow suit. The drug has also achieved breakthrough therapy designation in the US and PRIority MEdicines (PRIME) status in the EU. Alexion CEO Marc Dunoyer stated: “The approval of first-in-class, Factor D inhibitor Voydeya marks an important advancement in the treatment of PNH and builds on our leadership and commitment to bring forward innovation in complement science. “As the ALPHA trial suggests, dual complement pathway inhibition at Factor D and C5 may be an optimal treatment approach for this subset of patients with EVH, enabling them to continue with proven standard-of-care therapy.” Alexion is also exploring Voydeya’s potential as a monotherapy for geographic atrophy in a Phase II clinical trial. The FDA recently approved Alexion’s Ultomiris to treat adults with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder.

Pictured: AstraZeneca signage at its office in Sweden iStock, Wirestock AstraZeneca’s Alexion on Monday secured the fourth indication for Ultomiris, which can now be used to treat the rare autoimmune condition neuromyelitis optica spectrum disorder. Pictured: AstraZeneca signage at its office in Sweden/iStock, Wirestock The FDA on Monday approved the label expansion for AstraZeneca ’s complement inhibitor Ultomiris (ravulizumab-cwvz), allowing its use for the treatment of adult neuromyelitis optica spectrum disorder patients positive for anti-AQP4 antibodies. Monday’s approval makes Ultomiris the first and only long-acting C5 complement inhibitor for this indication that provides patients with the possibility of living relapse-free, according to the company’s announcement. Marc Dunoyer, CEO of AstraZeneca’s rare disease unit Alexion, in a statement called Ultomiris a “transformative” treatment option for neuromyelitis optica spectrum disorder (NMOSD) with the “potential to eliminate relapses with a convenient dosing schedule every eight weeks.” Ultomiris’ label expansion is supported by data from the Phase III CHAMPION-NMOSD trial, a global, open-label and multicenter trial with 58 NMOSD patients enrolled, all of whom were confirmed to be positive for anti-AQP4 antibodies and had had at least one attack or relapse in the 12 months before screening. Given the potential long-term consequences of NMOSD relapses, AstraZeneca and Alexion could not ethically include a direct placebo arm into CHAMPION-NMOSD. Instead, the company used data from the placebo arm of the PREVENT trial for its other NMOSD therapy Soliris (eculizumab). Findings from CHAMPION-NMOSD were published in March 2023 in the journal Annals of Neurology . Data showed that Ultomiris met its primary efficacy endpoint, preventing relapse in all 58 treated patients over a median follow-up period of 73.5 weeks, compared to 20 relapses in PREVENT’s placebo arm. In relative terms, Ultomiris reduced the risk of relapse by 98.6% versus PREVENT’s placebo. In terms of safety, Ultomiris was overall well-tolerated and most treatment-emergent events in CHAMPION-NMOSD were mild or moderate in severity. Two patients treated with the complement inhibitor developed meningococcal infections, both of whom recovered with no sequelae. No patients died due to treatment toxicities. Affecting around 6,000 patients in the U.S., NMOSD is a rare autoimmune disorder that arises when the body’s immune system attacks the protective myelin sheaths surrounding neurons. NMOSD most often affects the central nervous system, particularly the spine and optic nerves, and to a lesser degree the brain. NMOSD manifests as weakness in the limbs, painful spasms, uncontrollable vomiting, bowel dysfunction and sleeping problems. Patients with NMOSD often experience unpredictable relapses including new or worsening neurological symptoms. Through its rare disease unit Alexion, AstraZeneca’s NMOSD portfolio includes Soliris, which is a monoclonal antibody that targets the C5 complement protein, suppressing a central cascade in the immune response and preventing the body from attacking the central nervous system. Ultomiris is also a monoclonal antibody that works via the same mechanism of action. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com .