Givinostat Hydrochloride

延缓疾病进展！DMD小分子疗法在欧盟获批Italfarmaco今日宣布，欧盟委员会（EC）已授予旗下创新口服组蛋白去乙酰化酶（HDAC）抑制剂Duvyzat（givinostat）有条件上市许可，与糖皮质激素联合使用，用于治疗年满6岁及以上、可行走的杜氏肌营养不良症（DMD）患者，无论其致病基因突变类型为何。此次批准主要基于EPIDYS临床3期试验的积极结果。该研究为一项多中心、随机、双盲、安慰剂对照试验，共纳入179名年龄在6岁及以上、可行走的DMD患儿，患者在接受糖皮质激素基础治疗的同时，额外服用Duvyzat或安慰剂。试验达成主要终点，在四阶楼梯爬升测试中，Duvyzat组表现出统计学显著且临床意义明确的改善。此外，Duvyzat在北极星步行评估（NSAA）和磁共振脂肪浸润评估等关键次要终点也表现良好，用药组在NSAA累计丧失项目数方面下降幅度减少约40%，显示其有望延缓疾病进展。Duvyzat的不良反应大多为轻中度。突破性单抗3期积极结果公布，有望年底获批上市大冢制药（Otsuka Pharmaceutical）今日公布其在研单抗sibeprenlimab治疗成人免疫球蛋白A肾病（IgAN）的3期VISIONARY研究预设中期分析结果。数据显示，sibeprenlimab治疗组在治疗9个月时，其24小时尿蛋白/肌酐比值（uPCR）相比安慰剂组显著下降51.2%（P<0.0001），表明该药可有效减少蛋白尿。根据新闻稿，该研究为迄今为止规模最大的IgAN临床3期试验之一。此外，sibeprenlimab在安全性方面表现良好，与此前报道数据一致。研究中，76.3%的sibeprenlimab治疗组患者出现治疗伴发不良事件（TEAE），而安慰剂组为84.5%；发生严重TEAE的比例分别为3.9%和5.4%。Sibeprenlimab是一种人源化单克隆抗体，它能阻断细胞因子A增殖诱导配体（APRIL）的作用。美国FDA在去年2月授予sibeprenlimab突破性疗法认定（BTD），并在今年5月受理该疗法的生物制品许可申请（BLA），用于治疗IgAN，并授予优先审评资格。该申请的PDUFA日期为2025年11月28日。参考资料：[1] European Commission Approves Duvyzat for the Treatment of Duchenne Muscular Dystrophy. Retrieved June 6, 2025 from https://www.globenewswire.com/news-release/2025/06/06/3095258/0/en/European-Commission-Approves-Duvyzat-for-the-Treatment-of-Duchenne-Muscular-Dystrophy.html[2] Otsuka Sibeprenlimab Phase 3 Data Show a Statistically Significant and Clinically Meaningful Proteinuria Reduction for the Treatment of Immunoglobulin A Nephropathy (IgAN). Retrieved June 6, 2025 from https://www.otsuka.co.jp/en/company/newsreleases/2025/20250606_1.html免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

Now approved in the EU, Duvyzat offers an important treatment option for delaying Duchenne muscular dystrophy (DMD) disease progression Duvyzat is an orally administered treatment for DMD in patients 6 years and older who are able to walk The approval is based on Phase 3 EPIDYS trial data that demonstrated meaningful treatment benefits in ambulant patients MILAN, Italy, June 06, 2025 – Italfarmaco S.p.A. announced today that the European Commission (EC) has granted conditional marketing authorisation for Duvyzat ® (givinostat), a novel histone deacetylase (HDAC) inhibitor. It is approved for the treatment of Duchenne muscular dystrophy (DMD) in ambulant patients 6 years and older, regardless of the underlying genetic mutation, when taken together with corticosteroids. The EC decision follows the positive opinion of the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) on the 25th of April, 2025. The approval applies to all 27 EU member states, as well as Iceland, Liechtenstein, and Norway. Italfarmaco is now working closely with national authorities and distribution partners to facilitate timely access to Duvyzat across the EU. “People living with DMD in Europe have long awaited new therapeutic options that can alter the course of this devastating disease. Until now, there have been limited approved treatments that address the underlying pathology of DMD across the broad patient population. That changes with the approval of Duvyzat, which slows disease progression and preserves muscle function — regardless of the gene mutation — by targeting disease mechanisms,” said Paolo Bettica, MD, PhD, Chief Medical Officer at Italfarmaco Group . “We are committed to working closely with health authorities and the DMD community to ensure timely access to this important new treatment across Europe.” “The EC’s approval of Duvyzat is a recognition of its therapeutic potential and a testament to Italfarmaco’s scientific excellence and commitment to innovation in rare diseases,” said Dr Francesco De Santis, President of Italfarmaco Holding and Chairman of Italfarmaco Group . “This milestone means that a broad range of patients with DMD have access to a new treatment. At Italfarmaco, this achievement reaffirms our focus on advancing therapies that can make a meaningful difference in people’s lives.” The approval is based on the positive results of the EPIDYS Phase 3 multicentre, randomised, double-blind, placebo-controlled trial (NCT02851797). In the EPIDYS study, a total of 179 ambulant boys six years of age or older received either Duvyzat twice daily or placebo, in addition to corticosteroid treatment. The EPIDYS study met its primary endpoint demonstrating a statistically significant and clinically meaningful difference in time to complete the four-stair climb assessment. Duvyzat also showed favourable results on key secondary endpoints including North Star Ambulatory Assessment (NSAA) and fat infiltration evaluation by magnetic resonance imaging. Specifically, Duvyzat treatment was associated with 40% less decline in cumulative loss of NSAA items, indicating Duvyzat’s potential to delay disease progression in affected individuals. Most adverse effects observed with Duvyzat were mild to moderate in severity. Results from this study were published in The Lancet Neurology in March 2024. 1 Long-term data from the ongoing EPIDYS extension study was compared to natural history cohorts using propensity score matching showing that the median age at loss of ambulation was 18.1 years in the Duvyzat group versus 15.2 years in controls. 2 The EC has granted Duvyzat conditional marketing authorisation in the EU. The approval makes Duvyzat available to ambulant DMD patients 6 years and older while Italfarmaco conducts additional clinical studies designed to further confirm and characterise its therapeutic benefit. Outside of the EU, Duvyzat was granted approval by the US Food and Drug Administration (FDA) in March 2024 for the treatment of DMD patients 6 years and older. In the UK, Duvyzat received approval by the Medicines and Healthcare products Regulatory Agency (MHRA) for patients 6 years and older who are ambulatory and granted conditional marketing approval for non-ambulatory patients. About Duchenne Muscular Dystrophy Duchenne muscular dystrophy (DMD) is a rare, progressive neuromuscular disorder caused by mutations in the DMD gene. Mutations in the DMD gene prevent the production of functional dystrophin, causing the dystrophin-associated protein complex (DAPC) to break down. This makes muscle fibres more vulnerable to damage and increases histone deacetylase (HDAC) levels in the muscle cells, blocking the activation of important genes needed for muscle maintenance and repair. As a result, muscle fibres experience ongoing damage, leading to chronic inflammation and poor regeneration. Over time, muscle cells die and are replaced by scar tissue and fat. 3-6 DMD primarily affects males, with symptoms typically appearing between the ages of two and five. As the condition progresses, muscle weakness worsens, leading to difficulty walking and eventually to loss of ambulation. Over time, the heart and respiratory muscles are also affected, which are the leading causes of premature death. 7 DMD is one of the most severe and common forms of childhood muscular dystrophy, with a global birth incidence of approximately 1 in 5,050 boys. 8 About Duvyzat ® Duvyzat was discovered through Italfarmaco’s research and development efforts in collaboration with Telethon and Duchenne Parent Project (Italy). Duvyzat is an orally administered histone deacetylase (HDAC) inhibitor that regulates the excessive HDAC activity characteristic of DMD muscles. By doing so, it helps restore the expression of key genes and biological processes essential for muscle maintenance and repair. Its mechanism of action is independent of the specific dystrophin gene mutation causing the disease. 9,10 About ITALFARMACO Founded in 1938 in Milan, Italy, Italfarmaco is a private global pharmaceutical company that has led the successful development and approval of many pharmaceutical products around the world. The Italfarmaco group has operations in more than 90 countries through directly controlled or affiliated companies. The company is a leader in pharmaceutical research, product development, production and commercialisation with proven success in many therapeutic areas including immuno-oncology, gynaecology, neurology, cardiovascular disease and rare diseases. Italfarmaco's rare disease unit includes programmes in Duchenne muscular dystrophy, Becker muscular dystrophy, amyotrophic lateral sclerosis and polycythaemia vera. Media enquiries: Anja Heuer / Adolfo Luna | +49 (0) 151 106 199 05 | italfarmaco@trophic.eu Other enquiries: Samantha Parker | Patient Advocacy and Communications Lead | RDEnquiries@italfarmacogroup.com References: Mercuri, E, Vilchez, JJ, Boespflug-Tanguy, O, Zaidman, CM, Mah, JK, Goemans, N. Safety and efficacy of givinostat in boys with Duchenne muscular dystrophy (EPIDYS): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2024;23:393-403. Vandenborne, K., McDonald, C., Servais, L., Munell, F., Schara, U., Bertini, E., Comi, G., Blaschek, A., Cazzaniga, S., Bettica, P. U., & Mercuri, E. (2025, March). Givinostat in Duchenne muscular dystrophy: Effect on disease milestones [Poster presentation]. MDA Clinical & Scientific Conference, Dallas, TX. https://www.mdaconference.org/abstract-library/givinostat-in-duchenne-muscular-dystrophy-effect-on-disease-milestones/ ​Sandonà M, Cavioli G, Renzini A, et al. Histone Deacetylases: Molecular Mechanisms and Therapeutic Implications for Muscular Dystrophies. Int J Mol Sci. 2023;24(5):4306. https://doi.org/10.3390/ijms24054306 . Consalvi S, Saccone V, Giordani L, Minetti G, Mozzetta C, Puri PL. Histone Deacetylase Inhibitors in the Treatment of Muscular Dystrophies: Epigenetic Drugs for Genetic Diseases. Mol Med. 2011;17(5):457–465. https://doi.org/10.2119/molmed.2011.00049 . Bez Batti Angulski A, Hosny N, Cohen H, et al. Duchenne muscular dystrophy: disease mechanism and therapeutic strategies. Front Physiol. 2023;14:1183101. https://doi.org/10.3389/fphys.2023.1183101 . Giuliani G, Rosina M, Reggio A. Signaling pathways regulating the fate of fibro/adipogenic progenitors (FAPs) in skeletal muscle regeneration and disease. FEBS J. 2022;289(21):6484–6517. https://doi.org/10.1111/febs.16080 . Walter MC, Reilich P. Recent developments in Duchenne muscular dystrophy: facts and numbers. J Cachexia Sarcopenia Muscle. 2017;8(5):681–685. https://doi.org/10.1002/jcsm.12245 . Crisafulli S, Sultana J, Fontana A, Salvo F, Messina S, Trifirò G. Global epidemiology of Duchenne muscular dystrophy: an updated systematic review and meta-analysis. Orphanet J Rare Dis. 2020;15(1):141. https://doi.org/10.1186/s13023-020-01430-8 . Comi G, Bertini E, Vita G, et al. S22.008: Development of the histone deacetylases inhibitor Givinostat in Duchenne Muscular Dystrophy. Poster. Neurology. 2018;90(15 (Supplement)). Licandro SA, Crippa L, Pomarico R, et al. The pan HDAC inhibitor Givinostat improves muscle function and histological parameters in two Duchenne muscular dystrophy murine models expressing different haplotypes of the LTBP4 gene. Skelet Muscle. 2021;11(1):19. https://doi.org/10.1186/s13395-021-00273-6 . 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