Asfotase alpha

AstraZeneca’s experimental enzyme replacement therapy generated mixed results in three late-stage trials targeting a rare genetic condition called hypophosphatasia that can cause soft and weak bones. The treatment, efzimfotase alfa, is being developed as a next-generation version of AstraZeneca’s blockbuster drug Strensiq to extend the company’s dominance in hypophosphatasia, which affects about three in 100,000 people and can leave patients with pain and fatigue, lost teeth and other symptoms. On Tuesday, AstraZeneca said the experimental drug failed a Phase 3 trial in adults and adolescents. But two other trials had positive readouts. The HICKORY trial studied hypophosphatasia patients 12 years and older who hadn’t previously been treated with Strensiq, the only approved drug for the disease. Efzimfotase alfa showed an improvement compared with placebo on a six-minute walk test — the trial’s primary endpoint — but the difference wasn’t statistically significant. AstraZeneca blamed “better-than-expected results” in a placebo group of adult-onset patients. There were signs of efficacy in the data, AstraZeneca said. A combination of prespecified subgroups including adolescents and adults with pediatric-onset disease “showed nominally statistically significant and clinically meaningful benefits in mobility,” it said, though a company spokesperson declined to go into further detail. Strensiq sold $1.7 billion last year, and is currently approved for patients with infantile- and juvenile-onset disease. AstraZeneca is going after an even wider group with its new drug, targeting “the totality of the population,” strategy chief Marc Dunoyer said on the company’s fourth-quarter earnings call last month. The clinical program was its first to include both pediatric- and adult-onset disease. On last month’s earnings call, Dunoyer said that efzimfotase alfa could be worth “several times the value of Strensiq” if it demonstrates efficacy and safety in the total population, in part because it’s designed to have less frequent dosing. Dunoyer also serves as CEO of AstraZeneca’s Alexion unit. In two other Phase 3 trials of efzimfotase alfa in pediatric patients between 2 and 12 years old, AstraZeneca had positive results. In a trial called MULBERRY, the drug showed a statistically significant improvement in bone health compared with placebo. And in the CHESTNUT trial, which was designed to measure efzimfotase alfa’s safety in children who switched from Strensiq, the new drug was well-tolerated. AstraZeneca said it will share the results with global regulators. Jefferies analysts wrote in a note to investors on Tuesday that the “opportunity remains intact” for efzimfotase alfa, as there is “unmet need, adherence issues exist with Strensiq and manufacturing is more efficient with efzimfotase alfa.”

注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需要得到授权。 3月31日，阿斯利康旗下罕见病公司Alexion宣布，其新型酶替代疗法efzimfotase alfa（ALXN1850）治疗低磷酸酯酶症（HPP）的全球III期临床项目取得积极顶线结果。这项包含三项试验的大规模研究共纳入196名患者，覆盖22个国家，横跨儿童、青少年及成人全年龄段人群。这一里程碑式的数据读出，标志着这款旨在“升级”现有标准疗法的在研新药，距离解决HPP患者未被满足的临床需求更近了一步。 截图来源：阿斯利康官网 01 直击治疗痛点 更低频率、更小体积的“下一代”ERT 低磷酸酯酶症（HPP）是一种由碱性磷酸酶（ALP）活性缺乏引起的罕见、慢性遗传性代谢疾病，严重影响骨骼矿化与肌肉功能。目前，阿斯利康已上市的Strensiq是该领域的标准治疗药物，但其需每周多次皮下注射且注射体积较大的特点，给患者尤其是儿童带来了沉重的生理负担。 全球药物研发数据库（更多内容点击小程序查看） Efzimfotase alfa正是针对这一痛点设计的“下一代”酶替代疗法（ERT）。其独特的工程化改造使得药物能够通过每两周一次的皮下注射维持疗效，且注射体积显著小于Strensiq。这种给药方案的优化，有望极大地提升患者的依从性与生活质量，重塑HPP的长期管理模式。 02 III期数据深度解析 儿科全垒打，成人亚组显效 此次公布的III期项目由三项关键试验组成，结果呈现出显著的“年龄分层”特征： 儿科人群（2至<12岁）：全面达标，夯实疗效 MULBERRY研究（初治儿童）：达到主要终点。在第25周，通过放射学总体印象变化（RGI-C）评分评估，efzimfotase alfa组骨健康较安慰剂组显示出统计学显著且具有临床意义的改善。佝偻病严重程度评分（RSS）等关键次要终点同样显著改善，6分钟步行试验（6MWT）及运动熟练度数据进一步佐证了其临床获益。 全球药物研发数据库（更多内容点击小程序查看） CHESTNUT研究（Strensiq转换儿童）：验证了换药的安全性。结果显示efzimfotase alfa耐受性良好，且在第25周成功维持了此前Strensiq治疗带来的骨健康获益，未出现疗效回落。 青少年及成人：成人组受干扰，长病程亚组获益明确 HICKORY研究（初治青少年/成人）：由于成人期发病（AOHPP）安慰剂组患者的6MWT表现优于历史预期，导致主要终点未达统计学显著性。然而，探索性分析揭示了重要信号：在儿童期发病（COHPP）的青少年和成人预设亚组中，efzimfotase alfa在6MWT（移动能力）及疼痛减轻方面显示出名义上的显著获益。此外，整个研究人群在FACIT-疲劳量表上也观察到显著改善。 长期扩展数据：正在进行的开放标签扩展研究显示，第48周时主要及关键次要终点持续改善；安慰剂组患者在交叉换药并接受24周治疗后，也观察到了临床意义的逆转。 03 安全性优异 奠定监管申报基石 在所有三项III期研究（MULBERRY、CHESTNUT、HICKORY）中，efzimfotase alfa均表现出良好的耐受性及可接受的安全性特征。这一结果与现有ERT类药物的安全性谱系一致，为其后续向全球监管机构（包括FDA及EMA）提交上市申请奠定了坚实基础。 全球药物研发数据库（更多内容点击小程序查看） Alexion首席执行官Marc Dunoyer表示：“Efzimfotase alfa是首个在如此广泛的HPP患者群体中评估疗效的研究，涵盖了从儿童到成人、从骨骼到非骨骼表现的异质性特征。这些数据有力支持了它改变HPP治疗模式的潜力。” 结语 随着详细数据即将在后续医学会议上公布，efzimfotase alfa能否凭借“两周一次”的便捷性优势，在HPP领域实现对Strensiq的迭代，值得持续关注。对于阿斯利康而言，这不仅是一款新药的胜利，更是对其罕见病研发管线的有力补强。 END 本文为原创文章，转载请留言获取授权 近期热门资源获取 中国临床试验趋势与国际多中心临床展望-202505 2024年医药企业综合实力排行榜-202505 中国带状疱疹疫苗行业分析报告-202505 2023H2-2024H1中国药品分析报告-202504 2024年中国1类新药靶点白皮书-202503 中国AI医疗健康企业创新发展百强榜单-202502 2024年FDA批准上市的新药分析报告-202501 小分子化药白皮书（上）-202501 2024年中国医疗健康投融资全景洞察报告-202501 2024年医保谈判及市场分析报告-202501 近期更多摩熵咨询热门报告 识别下方二维码领取 联系我们，体验摩熵医药更多专业服务 会议 合作 报告 定制 数据库 咨询 数据 定制 媒体 合作 点击阅读原文，申请摩熵医药企业版免费试用！