A Phase 3, Randomized, Double-blinded, Placebo-controlled, Multicenter Study to Evaluate Efficacy and Safety of ALXN1850 Versus Placebo Administered Subcutaneously in Pediatric (2 to < 12 Years of Age) Participants With Hypophosphatasia Who Have Not Received Previous Treatment With Asfotase Alfa

The primary purpose of this study is to evaluate the efficacy of ALXN1850 versus placebo on radiographic outcomes in pediatric participants with HPP who have not previously been treated with asfotase alfa.

开始日期2024-05-14

申办/合作机构

Alexion Pharmaceuticals, Inc.

NCT06079372

/ Active, not recruiting临床3期

A Phase 3, Randomized, Open-label, Parallel-arm, Active-controlled, Multicenter Study to Evaluate Safety and Efficacy of ALXN1850 Versus Asfotase Alfa Administered Subcutaneously in Pediatric Participants (2 to < 12 Years of Age) With Hypophosphatasia (HPP) Previously Treated With Asfotase Alfa

The primary purpose of this study is to assess the safety and tolerability of ALXN1850 versus asfotase alfa in pediatric participants with HPP previously treated with asfotase alfa.

开始日期2024-04-02

申办/合作机构

Alexion Pharmaceuticals, Inc.

NCT06079281

/ Active, not recruiting临床3期

A Phase 3, Randomized, Double-blinded, Placebo-controlled, Multicenter Study to Evaluate Efficacy and Safety of ALXN1850 (Recombinant Alkaline Phosphatase) Administered Subcutaneously in Adolescent (12 to < 18 Years of Age) and Adult Participants With Hypophosphatasia Who Have Not Previously Been Treated With Asfotase Alfa

The primary objective of this study is to assess the efficacy of ALXN1850 versus placebo on functional outcomes in adolescent and adult participants with HPP who have not previously been treated with asfotase alfa.

开始日期2024-01-03

申办/合作机构

Alexion Pharmaceuticals, Inc.

100 项与 Efzimfotase alfa 相关的临床结果

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100 项与 Efzimfotase alfa 相关的转化医学

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100 项与 Efzimfotase alfa 相关的专利（医药）

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项与 Efzimfotase alfa 相关的文献（医药）

2026-01-01·JIMD reports

Efzimfotase Alfa Improves Respiratory Capacity in Muscle Tissue From a Mouse Model of HPP

Article

作者: Scavuzzo, Maria Concetta ; Voegtli, Walter ; Brandi, Maria Luisa ; Ruanova, Juan ; Decker, John ; Mazzantini, Maurizio ; Dunn, Derek ; Petryk, Anna ; De Tata, Vincenzo ; Conti, Francesco ; Devore, Denise

ABSTRACT:

Hypophosphatasia (HPP) is an inherited metabolic disease caused by deficient tissue‐nonspecific alkaline phosphatase (ALP) activity and characterized by skeletal and nonskeletal symptoms, including muscle weakness and fatigue. We hypothesized that mitochondrial respiration is impaired in muscle in HPP, independent of skeletal manifestations, and that the second‐generation ALP enzyme replacement therapy (ERT) efzimfotase alfa improves respiration. Akp2GW −/− mice were used for this purpose. Body weight, bone mineralization, and survival were validated in Akp2GW −/− mice versus Akp2 −/− mice, an established model of HPP. No significant differences were found, validating the Akp2GW −/− model. Respiratory outcomes were measured in skeletal muscle fiber bundles in age‐ and sex‐matched Akp2GW −/− and Akp2GW +/+ (wild‐type) mice; bone mineralization was assessed. Mean maximal respiration and mitochondrial spare respiratory capacity (SRC) in vehicle‐treated Akp2GW −/− mice were 37% and 30% of values from wild‐type mice, respectively, independent of skeletal manifestations. Efzimfotase alfa treatment significantly improved maximal respiration in tissue from Akp2GW −/− mice by 147% versus vehicle ( p = 0.0059) and improved SRC by 262% versus vehicle ( p = 0.0008). Mean maximal respiration and SRC in tissue from efzimfotase alfa‐treated Akp2GW −/− mice were 92% and 107%, respectively, of tissue from wild‐type mice. Cellular ultrastructure of muscle biopsies from people with HPP showed atypical mitochondrial morphology, including branching cristae and dispersed matrix. In a mouse model of HPP, we show that the altered mitochondrial respiration in skeletal muscle is improved by ERT and that HPP is characterized by altered muscle mitochondrial morphology in humans. Together, these data suggest ERT could improve muscular symptoms in HPP.

2024-09-26·JOURNAL OF BONE AND MINERAL RESEARCH

Safety, pharmacokinetics, and pharmacodynamics of efzimfotase alfa, a second-generation enzyme replacement therapy: phase 1, dose-escalation study in adults with hypophosphatasia

Article

作者: Dong, Qunming ; Voegtli, Walter ; Pan, Wei-Jian ; Dahir, Kathryn M ; Dunn, Derek ; Pradhan, Rajendra ; Pelto, Ryan ; Shannon, Amy ; Hasan, Jawad

Abstract:

Hypophosphatasia (HPP) is a rare, inherited metabolic disease caused by deficient activity of tissue-nonspecific alkaline phosphatase (TNSALP). Efzimfotase alfa (ALXN1850) is a second-generation TNSALP enzyme replacement therapy in development for HPP. This first-in-human open-label, dose-escalating phase 1 trial evaluated efzimfotase alfa safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity. Fifteen adults (5/cohort) with HPP received efzimfotase alfa in doses of 15 mg (cohort 1), 45 mg (cohort 2), or 90 mg (cohort 3) as one intravenous (i.v.) dose followed by 3 weekly subcutaneous (s.c.) doses. The primary objective was to assess safety and tolerability. Secondary objectives included pharmacokinetics, pharmacodynamics of ALP substrates known to be biomarkers of disease (inorganic pyrophosphate [PPi] and pyridoxal 5′-phosphate [PLP]) and immunogenicity. Treatment-emergent adverse events (TEAEs) occurred in 12 (80%) participants. Eight (53%) participants had injection site reactions (ISRs), observed after 10 of 41 (24%) s.c. injections. Most ISR TEAEs were mild and resolved within 1–2 d. Peak and total exposures of efzimfotase alfa increased in a greater-than-dose proportional manner over the range of 15–90 mg after i.v. and s.c. dosing. The arithmetic mean elimination half-life was approximately 6 d; absolute bioavailability was 28.6%–36.8% over the s.c. dose range of 15–90 mg. Dose-dependent reductions in plasma concentrations of PPi and PLP relative to baseline reached nadir in the first week after i.v. dosing and were sustained for 3–4 wk after the last s.c. dose. Four (27%) participants tested positive for antidrug antibodies (ADAs), 3 of whom were ADA positive before the first dose of efzimfotase alfa. ADAs had no apparent effect on efzimfotase alfa pharmacokinetics/pharmacodynamics. No participants had neutralizing antibodies. Efzimfotase alfa demonstrated acceptable safety, tolerability, and pharmacokinetic profiles and was associated with sustained reductions in biomarkers of disease in adults with HPP, supporting further evaluation in adult and pediatric patients.Registration: ClinicalTrials.gov NCT04980248 (https://clinicaltrials.gov/study/NCT04980248).

项与 Efzimfotase alfa 相关的新闻（医药）

2025-07-14

·BioSpace

AstraZeneca’s Baxdrostat Pushes Blood Pressure Lower in Phase III Trial

iStock, HuiLiu The drug came to AstraZeneca through its acquisition of CinCor Pharma in 2023, with the hopes of beefing up its cardiovascular and kidney disease pipelines. AstraZeneca’s $1.3 billion gamble on CinCor may be paying off, after baxdrostat, an aldosterone synthase inhibitor it got in the deal, achieved a “statistically significant and clinically meaningful” drop in blood pressure in a late-stage trial, according to a company press release Monday. The results are from the Phase III BaxHTN trial, comparing patients with uncontrolled or treatment-resistant hypertension on two different doses—1 mg or 2 mg—to patients who received placebo. All patients either received baxdrostat or placebo on top of standard of care. AstraZeneca originally took on baxdrostat via the $1.3 billion acquisition of CinCor Pharma in 2023 . The deal also involved regulatory milestones involving baxdrostat that could kick the total value up to $1.8 billion—a gamble for shareholders as baxdrostat had flunked a previous Phase II trial run by CinCor after failing to reduce blood pressure in patients with uncontrolled hypertension. Data from a subgroup, however, kept hopes alive that the drug could address the condition. AstraZeneca did not go into specific details of the results, only saying that both doses met the primary endpoint, which was the difference in seated systolic blood pressure (SBP) after 12 weeks. The trial also met secondary endpoints in specific patient subpopulations and other measures of hypertension. AstraZeneca said that the drug was “generally well tolerated with a favorable safety profile.” AstraZeneca plans to reveal more details at the European Society of Cardiology Congress in August 2025. Baxdrostat works by blocking aldosterone synthase, a protein responsible for synthesizing aldosterone, a steroid involved in sodium retention and maintaining homeostatic blood pressure in the body. AstraZeneca is also testing baxdrostat in a Phase III trial in combination with dapagliflozin for treating chronic kidney disease progression in patients with both kidney disease and high blood pressure. Baxdrostat is part of a spate of drugs that AstraZeneca is hoping will help the company hit $80 billion in revenue by 2030, according to analysts at Leerink Partners, writing in a note to investors in April. Those also include ceralasertib, currently in a Phase I trial for solid tumors; gefurulimab for treating myasthenia gravis; and efzimfotase alfa, currently in Phase III trials for hypophosphatasia.

临床3期临床结果临床2期并购临床1期

2025-01-15

·Pharmaceutical Technology

JP Morgan 2025: AstraZeneca promises a ‘catalyst-rich’ year ahead

AstraZeneca CFO Aradhana Sarin promised Phase III readouts and revenue growth in 2025 despite ongoing investigations of its Chinese operations. Credit: Bloomberg/ Getty Images AstraZeneca says a strong 2024 and stacked pipeline spells potential for further growth in 2025 as the company aims to bring in $80bn in revenue by 2030. CFO Aradhana Sarin outlined AstraZeneca’s plans at the 2025 JP Morgan Healthcare Conference in San Francisco on 15 January. The company maintains a confident outlook for the new year, said Sarin, despite its share price decline in the latter half of 2024. During her presentation, Sarin focussed on the company’s performance during the first nine months of 2024, during which AstraZeneca increased total revenue by 19% against the same period in 2023 . Additionally, cash flow rose by almost $1bn over the prior year. The company’s growth was largely attributed to its expanded clinical pipeline, which includes late-stage trials that have increased in number from 77 in 2022 to 91 in 2024. This year promises to be a “catalyst-rich” year for AstraZeneca, according to Sarin, with 21 new molecular entities (NMEs) in late-stage development, seven of which are expected to yield Phase III readouts within the next year. Among these are gefurulimab, being trialled in myasthenia gravis (NCT05556096), and efzimfotase alfa, trialled in hypophosphatasia (NCT06079281), the progress of which Sarin attributed to accelerated recruitment rates. Sarin did, however, note negatively impacted revenues in China given ongoing investigations of AstraZeneca’s operations in the country by authorities. On 30 October 2024, AstraZeneca’s Chinese operations president Leon Wang stood down and was detained along with other current and former employees amidst accusations of insurance fraud, data breaches, and import of unlicenced medicines. Revenues for AstraZeneca in the US, in comparison, increased by 20% in the first nine months of 2024, comprising 43% of total revenue and are expected to account for half of the company’s revenues by 2030 according to Sarin. She identified respiratory and immunology as the company’s foremost sectors, growing by 39% in Q4 of 2024. Additionally, she said assets like Breztri (budesonide + formoterol fumarate + glycopyrrolate) and Fasenra (benralizumab) are positioned for indication expansion into severe asthma and chronic obstructive pulmonary disorder (COPD), respectively, during 2025. Sarin said AstraZeneca’s capital allocation priorities are unchanged for the coming year and that the company remains focussed on antibody-drug conjugates, bispecific antibodies, and cell therapies, in addition to continuing its foray into the metabolic and gene editing space. Like many other companies that rose to prominence during the Covid-19 pandemic, AstraZeneca has made concerted efforts to break into the obesity market, and has tried going through the deal rout with its potential acquisition agreement with SixPeaks Bio , announced in May 2024.

并购临床3期

2024-12-11

·蒲公英Ouryao

又一药品纳入“关爱计划”

转自：国家药监局审评中心编辑：随风飞舞 2024年12月11日，国家药监局审评中心发布了关爱计划项目公告，涉及品种为ALXN1850注射液，拟用于治疗低磷酸酯酶症。关于《以患者为中心的罕见疾病药物研发试点工作（“关爱计划”）申报指南》，请点击：CDE:关爱计划发布、即日起执行！依据《以患者为中心的罕见疾病药物研发试点工作计划（“关爱计划”）申报指南》，现将ALXN1850注射液纳入“关爱计划”，试点项目的基本信息如下：品种名称：ALXN1850注射液申报单位：阿斯利康全球研发（中国）有限公司适应症：拟用于治疗低磷酸酯酶症（HPP）。申报阶段：C阶段-关键研究前阶段。工作要点：在中国参与的关键性国际多中心临床试验中，选择多个COA指标作为研究终点评估本品的临床获益。往期信息： 01 Fitusiran注射液依据《以患者为中心的罕见疾病药物研发试点工作（“关爱计划”）申报指南》，现将Fitusiran注射液纳入“关爱计划”，试点项目的基本信息如下：品种名称：Fitusiran注射液申报单位：GenzymeCorporation 适应症：本品适用于作为常规预防治疗，用于有或无凝血因子VIII或IX抑制物的血友病A或B的成人患者和≥12岁青少年患者，以预防或减少出血的发生频率。申报阶段：D阶段-上市申请前/上市申请阶段。工作要点：计划在临床试验中开展患者定性访谈研究，在上市后研究阶段收集与评估安全性、有效性及在使用fitusiran前后血友病治疗体验等相关的患者体验数据。 02 羟钴胺注射液依据《以患者为中心的罕见疾病药物研发试点工作（“关爱计划”）申报指南》，现将羟钴胺注射液纳入“关爱计划”，试点项目的基本信息如下：品种名称：羟钴胺注射液申报单位：华润双鹤药业股份有限公司适应症：本药物适用于儿童甲基丙二酸血症（MethylmalonicAcidemia，MMA）伴或不伴同型半胱氨酸血症患者代谢紊乱的治疗。申报阶段：A阶段-研发立项阶段。工作要点：在研发立项阶段，进行患者详细调研问卷收集，为后续药物的开发、剂型等提供依据；同时进一步丰富MMA疾病自然史的数据。

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100 项与 Efzimfotase alfa 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
低碱性磷酸酶血症	临床3期	中国	Alexion Pharmaceuticals, Inc.	2024-01-03
低碱性磷酸酶血症	临床3期	日本	Alexion Pharmaceuticals, Inc.	2024-01-03
低碱性磷酸酶血症	临床3期	阿根廷	Alexion Pharmaceuticals, Inc.	2024-01-03
低碱性磷酸酶血症	临床3期	澳大利亚	Alexion Pharmaceuticals, Inc.	2024-01-03
低碱性磷酸酶血症	临床3期	巴西	Alexion Pharmaceuticals, Inc.	2024-01-03
低碱性磷酸酶血症	临床3期	加拿大	Alexion Pharmaceuticals, Inc.	2024-01-03
低碱性磷酸酶血症	临床3期	法国	Alexion Pharmaceuticals, Inc.	2024-01-03
低碱性磷酸酶血症	临床3期	德国	Alexion Pharmaceuticals, Inc.	2024-01-03
低碱性磷酸酶血症	临床3期	以色列	Alexion Pharmaceuticals, Inc.	2024-01-03
低碱性磷酸酶血症	临床3期	意大利	Alexion Pharmaceuticals, Inc.	2024-01-03

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04980248 (Pubmed \| J Bone Miner Res) 人工标引	临床1期	低碱性磷酸酶血症 inorganic pyrophosphate \| pyridoxal 5'-phosphate	15	Efzimfotase alfa 15 mg	製窪夢夢膚壓窪夢壓積(築廠積膚淵顧顧選積壓) = 積壓構憲壓簾築窪蓋簾觸醖膚窪襯窪襯繭齋顧 (窪襯襯網製鏇壓淵鹽襯 ) 更多	积极	2024-08-13