Anifrolumab-FNIA

9月17日，阿斯利康对外公布，对中度至重度系统性红斑狼疮（SLE）患者进行的III期TULIP-SC试验的一项预先设定的中期分析显示，阿斯利康的Saphnelo（anifrolumab）皮下给药与安慰剂相比，在疾病活动度方面表现出统计学显著且具临床意义的降低。该中期分析中观察到的安全性特征与Saphnelo静脉输注给药的已知临床特征一致。 TULIP-SC试验评估了Saphnelo皮下给药对比安慰剂，在接受标准治疗（口服皮质类固醇、抗疟药和/或免疫抑制剂）的中度至重度活动性、自身抗体阳性SLE参与者中的有效性和安全性。 SLE影响全球超过340万人，可累及任何器官，导致许多患者出现使人衰弱的症状、不可逆的器官损伤以及与健康相关的生活质量下降。 虽然口服皮质类固醇常被用于缓解SLE患者的症状，但它们会带来不良事件且仅有短期益处，并未针对疾病的根本驱动因素，阻碍了患者获得充分的疾病控制和实现缓解。 近期更新的临床指南提升了以实现缓解或低疾病活动度为治疗目标以及尽量减少口服皮质类固醇使用的重要性。 医学博士、公共卫生硕士Susan Manzi（阿勒格尼健康网络医学研究所所长、费城德雷塞尔大学医学院教授，TULIP-SC试验的主要研究者）表示：“皮下注射anifrolumab的今日结果强化了该疗法的有效性和安全性，并为这一重要生物制剂以更灵活、更方便的方式惠及更广泛的患者群体提供了机会。尽管指南推荐早期干预和生物制剂治疗，但仍有太多系统性红斑狼疮患者依赖口服皮质类固醇，而这会 contribute to （导致）不可逆的器官损伤。” 阿斯利康生物制药研发执行副总裁Sharon Barr表示：“今日的消息使我们向让更多系统性红斑狼疮患者获得Saphnelo具有临床意义的益处又迈进了一步。TULIP-SC的结果尤为重要，因为目前约半数使用生物制剂的系统性红斑狼疮患者已接受自我给药的皮下注射选项治疗。对于Saphnelo，我们希望将缓解确立为更多患者可实现的治疗目标，并且我们正积极与监管机构合作，以尽快将这一新的给药选择带给患者。” TULIP-SC试验中的疾病活动度降低是通过第52周时基于不列颠群岛狼疮评估组的综合狼疮评估（BICLA）来衡量的。BICLA要求所有在基线时有疾病活动的器官均有改善，且无新的 flares （发作）。 TULIP-SC的中期结果正在接受监管审查，并将于2025年10月24日至29日举行的美国风湿病学会（ACR） Convergence 2025年会上公布。 Saphnelo静脉输液剂型已在包括美国、欧盟和日本在内的全球70多个国家获批用于治疗中度至重度SLE，其他国家的审评正在进行中。截至目前，全球已有超过38,000例患者接受了Saphnelo的治疗。关于系统性红斑狼疮系统性红斑狼疮（SLE）是一种自身免疫性疾病，免疫系统会攻击体内的健康组织。它是一种慢性且复杂的疾病，具有多种临床表现，可影响许多器官，并可引起一系列症状，包括疼痛、皮疹、疲劳、关节肿胀和发热。 全球有超过340万人受到SLE的影响，并且它是美国年轻女性死亡的主要原因之一。患有SLE可能是痛苦的、使人衰弱的，对患者的心理和经济福祉产生深远影响，并且不成比例地侵害处于黄金年龄的女性以及亚裔、黑人或西班牙裔种族/族裔背景的人群。 据估计，由于长期使用皮质类固醇和疾病活动，约50%的SLE患者在诊断后五年内出现不可逆的器官损伤。 即使是每日类固醇用量的少量减少（例如1毫克/天）也能降低器官损伤的风险。关于TULIP-SC试验 TULIP-SC是一项III期、多中心、随机、双盲、安慰剂对照研究，旨在评估在接受标准治疗的中度至重度活动性、自身抗体阳性SLE参与者中，皮下注射anifrolumab对比安慰剂的疗效和安全性。 招募的患者年龄在18至70岁之间，并且必须一直在服用以下一种或任何组合的药物：口服皮质类固醇、抗疟药和/或免疫抑制剂。在该试验中，367名接受标准治疗的参与者以1:1的比例随机分组，接受通过配套的预充式注射器每周一次皮下注射120mg剂量的anifrolumab或安慰剂。当前220名参与者达到52周时，进行了一项计划中的中期分析。该试验还包括对完成52周治疗期的参与者进行的为期52周的开放标签扩展期。关于Saphnelo Saphnelo（anifrolumab）是一种首创的、全人源单克隆抗体，可与I型干扰素（IFN）受体的亚基1结合，从而阻断I型IFN的活性。I型IFN，如IFN-α、IFN-β和IFN-κ，是参与调节SLE所涉及的炎症通路的细胞因子。 Saphnelo正在持续于I型IFN起关键作用的疾病中进行评估，包括针对皮肤红斑狼疮、肌炎、系统性硬化症和狼疮性肾炎的III期试验。 立即扫码加入药事纵横交流群

After multiple failed trials of Fasenra in COPD, AstraZeneca will move on to advancing two other biologics—Tezspire and tozorakimab—in the indication. After another swing and a miss for AstraZeneca's Fasenra in chronic obstructive pulmonary disease (COPD), the company is pivoting to other options in its portfolio that might have potential to treat the respiratory condition.In the phase 3 RESOLUTE trial, which included patients with elevated blood eosinophil counts, Fasenra showed numerical improvement in reducing COPD exacerbations but did not reach the statistical significance needed for the study to hit its primary endpoint.The results arrive seven years after Fasenra came up short in two phase 3 COPD trials and 11 years after the IL-5 receptor agonist failed to make the grade in a phase 2a study in the indication.“COPD, which remains a leading cause of death worldwide, is a complex, heterogeneous disease, and we continue to advance other promising approaches in our pipeline to address the unmet needs of patients,” Sharon Barr, who heads up R&D for AZ’s biopharmaceuticals unit, said in a Sept. 17 press release.The company has advanced two other biologics in the indication. Blockbuster asthma treatment Tezspire, a thymic stromal lymphopoietin (TSLP) blocker, is under investigation in two phase 3 trials, while IL-33 tozorakimab is in a phase 3 COPD study that's expected to read out in the first half of 2026. Despite earlier setbacks, AZ had hopes of succeeding with RESOLUTE based on analysis of the results from its prior Fasenra studies in COPD. RESOLUTE included 689 participants with elevated blood eosinophil counts and a history of at least two COPD exacerbations in the year preceding trial enrollment. The participants also were current or former smokers and were on triple-inhaled maintenance therapy.The primary endpoint was the annual rate of moderate or severe COPD exacerbations. Participants remained on their background therapy and received either placebo or 100-mg Fasenra every four weeks for three months, followed by a 100-mg dose every eight weeks. AZ was hoping to compete with other companies, which gained approvals for their biologic treatments in the indication. Sanofi and Regeneron scored a COPD nod for Dupixent in September 2024. Then, four months ago, GSK achieved a similar FDA approval for Nucala.While the results for the trial are “disappointing,” they do not change AZ's peak sales outlook for the brand, which currently stands at a range between $3 billion and $5 billion, a company spokesperson said in an email. Fasenra, which has been on the market for eight years, achieved (PDF) sales of $1.7 billion last year, up by 12% compared to 2023. AZ has a medicine on the market for COPD. Breztri Aerosphere, which was approved as an inhaled maintenance therapy in 2020, generated sales of $972 million last year. The treatment is a combination of the three ingredients included in AZ’s dual-drug regimens Symbicort and Bevespi.AZ’s Saphnelo excels in SubQ studyIt wasn’t all bad news from AZ on Wednesday, as interim results from a phase 3 trial of patients with systemic lupus erythematosus (SLE) showed that subcutaneous (SC) administration of Saphnelo topped placebo. The self-administration format of Saphnelo, which is infused under its current approval, showed a statistically significant and clinically meaningful reduction in disease activity, AZ said in a release. The safety profile of injectable Saphnelo measured up to that seen in previous studies of the drug's intravenous presentation, which was approved in lupus in 2021.The results “provide the opportunity for this important biologic to reach a wider group of patients in a more flexible and convenient way,” said Drexel University's Susan Manzi, M.D., who served as principal investigator on AZ's trial, in the company's announcement. “Despite guidelines recommending earlier intervention and biologic treatments, too many people with systemic lupus erythematosus rely on oral corticosteroids, which contribute to irreversible organ damage.” Results from the trial are under regulatory review and will be presented during the American College of Rheumatology (ACR) annual meeting in October, AZ added.Saphnelo, which generated $304 million in sales in the first half of this year, is projected to achieve peak annual sales of between $1 billion and $3 billion. Future readouts for Saphnelo are on tap in lupus nephritis, systemic sclerosis, myositis and cutaneous lupus erythematosus.