Ravulizumab-CWVZ

Positive results from the global PREVAIL Phase III trial showed that gefurulimab met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) total score compared to placebo in adults with anti-acetylcholine receptor (AChR) antibody-positive (Ab+) generalised myasthenia gravis (gMG) at week 26. PREVAIL also met all secondary endpoints, including change from baseline in Quantitative Myasthenia Gravis (QMG) total score at week four and week 26.1 These data were presented at the Myasthenia Gravis Foundation of America (MGFA) Scientific Session during the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting in San Francisco, California.1 Gefurulimab demonstrated improvement from baseline in MG-ADL total score at week 26 compared to placebo (treatment difference: -1.6 [95% CI: -2.4, -0.8], p<0.0001). A clinically meaningful improvement was observed as early as week one, and was sustained through week 26.1 Additionally, a clinically meaningful improvement in key secondary endpoint, QMG total score, was seen as early as week four (treatment difference: -1.8 [ 95% CI: -2.5, -1.1], p<0.0001) and was sustained through week 26 (treatment difference: -2.1 [95% CI: -3.1, -1.1], p<0.0001).1 Kelly Gwathmey, MD, Associate Professor of Neurology, Chief of Neuromuscular Division, Virginia Commonwealth University, Richmond, VA, Vice Chair of the MGFA Medical & Scientific Advisory Council and principal investigator in the trial, said: “People living with gMG face fluctuating and often debilitating symptoms, including loss of muscle function and severe weakness. Results from the PREVAIL Phase III trial demonstrating early and lasting benefits in MG-ADL and QMG scores support the potential for gefurulimab to offer an efficacious and convenient self-administered treatment option that may help address the unpredictability of this disease.” Gianluca Pirozzi, Senior Vice President, Head of Development, Regulatory and Safety, Alexion, AstraZeneca Rare Disease, said: “Findings from PREVAIL offer valuable insight into how early and sustained complement inhibition with gefurulimab may translate into meaningful, functional improvement for people living with gMG. Improvements reflected in both patient- and physician-reported outcome measures further underscore the clinical relevance of these results. As one of the largest global Phase III trials in patients with AChR-Ab+ gMG, PREVAIL data reflect our commitment to advancing rigorous, patient-centred science that can transform care for people living with this debilitating and unpredictable disease worldwide.” Summary of primary endpoint LS mean change (95% CI) from RCT baseline in MG-ADL total score ***P<0.001; 2-sided nominal P values are reported for weeks 1-23 for the comparison of change from baseline between treatment groups. aBaseline is defined as the last available assessment value prior to the first dose of study intervention. BL, baseline; LS least squares; MG-ADL, Myasthenia Gravis Activities of Daily Living; RCT, randomized controlled treatment; SEM, standard error of the mean. Results from the PREVAIL Phase III trial showed treatment withgefurulimab was well-tolerated, and the safety profile was consistent with previous trials of C5 inhibitors eculizumab and ravulizumab in gMG. The percentage of participants with treatment emergent adverse events (TEAEs) was similar between those who received gefurulimab and placebo, and most TEAEs observed were mild to moderate in severity (grade 1 or 2). The most common TEAEs were injection site reactions (9.9%), headache (9.9%), and back pain (7.6%) in those treated with gefurulimab and headache (12.4%), diarrhoea (8.5%), and upper respiratory tract infection (7.8%) in those who received placebo.1 Notes gMG gMG is a rare autoimmune disorder characterised by loss of muscle function and severe muscle weakness.2 Eighty-five percent of people with gMG are AChR antibody-positive meaning they produce specific antibodies (anti-AChR) that bind to signal receptors at the neuromuscular junction (NMJ), the connection point between nerve cells and the muscles they control.3 This binding activates the complement system, causing the immune system to attack the NMJ, leading to inflammation and a breakdown in communication between the brain and the muscles.4 gMG can occur at any age, but it most commonly begins for women before the age of 40 and for men after the age of 60.5 Initial symptoms may include slurred speech, double vision, droopy eyelids and lack of balance; these can often lead to more severe symptoms as the disease progresses such as, impaired swallowing, choking, extreme fatigue and respiratory failure.6,7 PREVAIL (ALXN1720-MG-301) PREVAIL (ALXN1720-MG-301) is a global, Phase III, randomised, double-blind, placebo-controlled, parallel, multicentre study evaluating the safety and efficacy of gefurulimab in adults with generalised myasthenia gravis (gMG). The trial enrolled 260 patients from 20 countries across North America, Europe, Asia and the Pacific region. Participants were required to have a confirmed myasthenia gravis diagnosis at least three months prior to the screening visit with a positive serological test for autoantibodies against AChR and Myasthenia Gravis Foundation of America Clinical Classification Class II to IV at screening.8 Patients were randomised 1:1 to receive gefurulimab or placebo for a total of 26 weeks in the randomised controlled treatment period. Patients received a single weight-based loading dose on Day 1, followed by regular weight-based maintenance dosing beginning on Day 8 and once every week thereafter. The primary endpoint of the change from baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) total score, a patient-reported scale that assesses patients’ abilities to perform daily activities, was assessed at week 26 along with multiple secondary endpoints evaluating improvement in disease-related measures.8 Patients who completed the randomised controlled treatment period were eligible to continue into an open-label extension period evaluating the safety and efficacy of gefurulimab, which is ongoing.8 Gefurulimab Gefurulimab, an investigational complement C5 inhibitor, is a novel dual-binding nanobody optimised for subcutaneous self-administration in development as a treatment for AChR-Ab+ gMG. The investigational medication works by binding to the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. Concurrent binding of gefurulimab to serum albumin provides an extended half-life, enabling once-weekly dosing. Gefurulimab has been granted Orphan Drug Designation in the US for the treatment of myasthenia gravis. 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. References Corporate and financial

Kyverna\'s CEO said new data boost his confidence in the chances of phase 3 success.\n Kyverna Therapeutics has reported deep, sustained improvements in autoimmune disease patients who received a single dose of its CAR T-cell therapy KYV-101.The data come from the phase 2 part of a trial Kyverna is running to support the registration of the cell therapy in generalized myasthenia gravis (gMG). As of the data cutoff, the biotech had results for six patients with moderate to severe gMG. The patients, who had gMG for an average of 5.3 years, had tried immunosuppressant therapies such as FcRns and complement inhibitors in the past without success.Kyverna saw an eight-point improvement on the MG-ADL scale, which measures the impact of gMG on daily functions, in the three patients with 24 weeks of follow-up. The company compared the result to the 3.1- to 4.6-point reductions seen in trials of argenx’s Vyvgart and AstraZeneca’s Ultomiris, respectively.The KYV-101 data also compare favorably to the results on Amgen’s Uplizna and Cartesian Therapeutics’ Descartes-08, both of which are in development in gMG. Both companies have seen 4.2-point changes on the scale. Descartes-08 is an mRNA CAR-T therapy. But, whereas KYV-101 is a CD19 treatment with CD28 co-stimulation, Cartesian’s asset engages BCMA. MG-ADL is the primary efficacy endpoint in the phase 2 trial and one of two co-primary endpoints in the phase 3 part of the study. The other phase 3 primary endpoint is quantitative myasthenia gravis (QMG), another measure of disease severity. Kyverna saw a 7.7-point drop on QMG in the phase 2 trial, compared to declines of between 2.8 and 6.2 points in its rivals’ trials.Stanford Medicine’s Srikanth Muppidi, M.D., commented on the efficacy data on a call Kyverna held to discuss the results with analysts. Muppidi said the data are “quite promising” but flagged factors that could have affected the cross-trial comparisons. Patients in the Kyverna trial had a significant disease burden that was higher than in some phase 3 studies published to date, Muppidi said.Two of the three patients had minimal symptom expression by Week 24. Kyverna CEO Warner Biddle said on the call that all the other patients in the trial were trending toward minimal symptom expression. On the safety front, all six patients had cytokine release syndrome, a common side effect of CAR-Ts. Two of the cases were grade 2 and the other four were grade 1, indicating relatively mild effects. No patients had immune-effector-cell-associated neurotoxicity syndrome, another common CAR-T side effect. There were grade 3 and 4 cases of low neutrophils, a type of white blood cell, linked to lymphodepletion. Biddle said the data boost his confidence in chances of phase 3 success because the results exceeded the magnitude of effect assumed for the pivotal study’s primary endpoint. The biotech is enrolling 60 people in the phase 3 part of the study, which will compare KYV-101 to standard of care.Kyverna is part of a group of companies developing CAR T-cell therapies in gMG. The group includes Cartesian’s BCMA program and CD19-directed CAR-T therapies that are in clinical development at Cabaletta Bio and Novartis.