A Randomized, Double-blind, Multicenter Study to Demonstrate Equivalent Efficacy and to Compare Safety and Immunogenicity of a Biosimilar Ustekinumab (AVT04) and Stelara® in Patients With Moderate to Severe Chronic Plaque-type Psoriasis

Safety and Efficacy study of AVT04 (Alvotech Biosimilar to Ustekinumab), in patients with moderate to severe plaque psoriasis

开始日期2021-06-03

申办/合作机构

Alvotech Swiss AG

NCT04744363 / Completed临床1期

Phase 1, FIH, Randomized, Double-blind, Single-dose, Parallel-group, 3-arm Study Comparing the PK, Safety, Tolerability, and Immunogenicity Profiles of AVT04, EU-approved Stelara®, and US-licensed Stelara® in Healthy Adult Subjects

Protocol Title:
A Phase 1, first-in-human, randomized, double-blind, single-dose, parallel-group, 3-arm study comparing the pharmacokinetic, safety, tolerability, and immunogenicity profiles of AVT04, EU approved Stelara®, and US-licensed Stelara® in healthy adult subjects
Short Title:
A first-in-human randomized, double-blind study to compare AVT04 with EU-approved Stelara and US-licensed Stelara as a single-dose subcutaneous injection in healthy adult subjects
Rationale:
Alvotech (hereafter, the Sponsor) is developing AVT04 globally as a proposed biosimilar to the reference product Stelara (ustekinumab) for subcutaneous (SC) use. This is a first-in-human (FIH) clinical study with AVT04. The study aims to demonstrate pharmacokinetic (PK) similarity of the proposed biosimilar test product AVT04 and the reference products EU approved Stelara and US-licensed Stelara, in addition to evaluating the safety and tolerability of AVT04, when administered as a single 45 mg/0.5 mL SC dose.

开始日期2021-05-25

申办/合作机构

Alvotech Swiss AG

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100 项与乌司奴单抗生物类似药（Alvotech）相关的临床结果

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100 项与乌司奴单抗生物类似药（Alvotech）相关的转化医学

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100 项与乌司奴单抗生物类似药（Alvotech）相关的专利（医药）

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项与乌司奴单抗生物类似药（Alvotech）相关的文献（医药）

2023-08-03·Expert opinion on biological therapy

Randomized, double-blind, multicenter study to evaluate efficacy, safety, tolerability, and immunogenicity between AVT04 and the reference product ustekinumab in patients with moderate-to-severe chronic plaque psoriasis

Article

作者: Otto, Hendrik ; Berti, Fausto ; Stroissnig, Heimo ; Feldman, Steven R ; Haliduola, Halimu N ; Duijzings, Paul ; Leutz, Steffen ; Ruffieux, Ruth ; Reznichenko, Nataliya

BACKGROUND:

This study compared efficacy, safety, tolerability, pharmacokinetics (PK), and immunogenicity between AVT04 and reference product (RP) ustekinumab (Stelara®) in patients with moderate-to-severe chronic plaque psoriasis (PsO).

PATIENTS AND METHODS:

This multicenter, double-blind, 52-week study randomized patients in 1:2 ratio to AVT04 or RP. At week 16, responsive patients (≥50% improvement in psoriasis area and severity index (PASI)) previously on AVT04 continued on AVT04, while those on RP were re-randomized 1:1 to switch to AVT04 or stay on RP. The primary endpoint was a percent improvement in PASI from baseline to week 12. Therapeutic equivalence was demonstrated if the confidence interval (CI) for the adjusted difference in means was contained within the equivalence margins; ±10% (90%CI).

RESULTS:

Of the 581 patients initially randomized (AVT04:RP, 194:387), 575 completed week 16 and 544 completed end of study visit. The percent PASI improvement for AVT04 vs RP was 87.3% vs 86.8% (CI: -2.14%, 3.01%); study met its primary endpoint. Efficacy, safety and PK profiles were comparable across treatment arms throughout the entire study duration, and the incidence of antibodies to ustekinumab had no clinically meaningful impact.

CONCLUSION:

This study demonstrates the therapeutic equivalence between AVT04 and RP in patients with moderate-to-severe chronic PsO, with similar safety and tolerability.

TRIAL REGISTRATION:

NCT04930042; EudraCT Number: 2020-004,493-22.

2023-05-04·Expert opinion on investigational drugs

A randomized, double-blind, 3-arm, parallel study assessing the pharmacokinetics, safety, tolerability and immunogenicity of AVT04, an ustekinumab candidate biosimilar, in healthy adults

Article

作者: Otto, Hendrik ; Hamilton, Paul ; Haliduola, Halimu N ; Wynne, Christopher ; Duijzings, Paul ; McLendon, Kristi ; Smith, Matthew ; Berti, Fausto ; Stroissnig, Heimo ; Sattar, Abid ; Leutz, Steffen ; Ruffieux, Ruth

BACKGROUND:

This study assessed pharmacokinetic (PK) similarity, safety, and immunogenicity of AVT04, a candidate biosimilar, compared with reference product (RP) ustekinumab (EU-approved and US-licensed Stelara®).

METHODS:

Healthy subjects (N = 298) were randomized 1:1:1 to receive one 45 mg dose of AVT04, EU-RP, or US-RP. The primary PK parameters were Cmax and AUC0-inf. PK similarity was demonstrated if the 90% confidence intervals (CI) for the ratio of geometric means were all contained within the prespecified margins of 80% and 125%. Additional PK parameters, including AUC0-t, were also assessed. Safety and immunogenicity were also assessed until Day 92.

RESULTS:

After pre-specified protein content normalization, the 90% CI for the ratio of geometric means for primary PK parameters were all contained within the pre-specified bioequivalence margins of 80% and 125%, supporting demonstration of PK similarity between AVT04 and both EU- and US-RP. Secondary PK parameters supported the analysis. Safety and immunogenicity profiles were comparable across all three treatment arms, although the study was not powered to detect small differences in these parameters.

CONCLUSION:

Results supported a demonstration of PK similarity between candidate biosimilar AVT04, US-RP and EU-RP. Similar safety and immunogenicity were also shown.Clinical trial registration: www.clinicaltrials.gov identifier is NCT04744363.

项与乌司奴单抗生物类似药（Alvotech）相关的新闻（医药）

2024-06-11

·BioSpace

Stada Bags European Rights from Alvotech to Biosimilar of Amgen Blockbusters

Pictured: Businessmen shaking hands after closing a deal/iStock, Tippapatt Alvotech and Stada have expanded their alliance to include a clinical-stage biosimilar of Amgen’s blockbuster bone drugs Prolia and Xgeva, the companies announced Tuesday. Prolia and Xgeva have the same active ingredient, denosumab, but are approved in different indications. Amgen provides Prolia as a treatment for osteoporosis, both in postmenopausal women at high risk of fracture and in men who need to increase bone mass. Physicians mainly use Xgeva to prevent fractures and other skeletal events in patients with bone metastases from solid tumors and multiple myeloma. The products are among Amgen’s best-selling drugs, with the company reporting Prolia and Xgeva sales of $4 billion and $2.1 billion, respectively, in 2023. Both products are still growing. Prolia sales grew 8% in the first quarter of 2024, while revenues from Xgeva rose 5%. Alvotech and Stada are preparing to provide patients and physicians with biosimilar alternatives to Prolia and Xgeva. Tuesday, Alvotech said Stada has gained semi-exclusive commercial rights for its proposed biosimilar copy of the Amgen drugs in Europe, including Switzerland and the U.K. Stada has also secured exclusive rights to the biosimilar candidate in some markets in Central Asia and the Middle East. Investigators are comparing Alvotech’s AVT03 biosimilar candidate to denosumab in postmenopausal women with osteoporosis in a Phase III clinical trial. The study is scheduled to finish this year. Alvotech remains responsible for developing and manufacturing AVT03. The patents protecting Prolia and Xgeva in Europe expired in 2022 and Sandoz received approval for the first biosimilar copies in the region in May 2024. Sandoz could launch its denosumab biosimilar in the U.S. in May 2025. Organon, which is partnered with Shanghai Henlius Biotech, has applied for approval of another denosumab biosimilar in the European Union. Stada secured rights to AVT03 as part of a broader set of changes to its partnership with Alvotech. The companies partnered to commercialize seven biosimilars in Europe in 2019, leading to the approval of the Humira (adalimumab) biosimilar Hukyndra in 2021. Stada extended its rights to Hukyndra to include countries in Central Asia in parallel to the AVT03 deal. Alvotech also granted Stada rights to a biosimilar of Stelara (ustekinumab) in parts of Central Asia. Stada already had rights to the product, Uzpruvo, in the E.U., where it received authorization earlier this year. Alvotech and Stada are preparing to launch Uzpruvo in Europe. Stada is returning rights to a proposed biosimilar to the eye disease drug Eylea (aflibercept) to Alvotech. The action follows Stada’s launch of a biosimilar of Lucentis (ranibizumab), a drug that competes with Eylea. Nick Paul Taylor is a freelance pharmaceutical and biotech writer based in London. He can be reached on LinkedIn.

上市批准临床3期生物类似药引进/卖出临床结果

2024-06-01

·药融圈

一年做95项license交易，全球仿制药巨头也有春天

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。任何文章转载需得到授权。来自德国🇩🇪史达德（STADA）集团，承载着严谨的德国药剂师基因的制药企业。公司始于1895年，一群远见卓识的药剂师携手在德累斯顿创立德国药剂师协会，这标志着史达德的诞生。该集团名字源自“Standardpr ParateDeutscher Apotheker”，即药剂师所制造的标准产品的代称。 STADA目前拥有11466名员工，其中7000+名技术研发人员，在1903年就首次制定了从药用原料、生产工艺到药品包装全过程的标准化生产法规。公司聚焦于仿制药、特药、消费者健康三大模块。史达德在2023年保持增长势头，销售额和利润均实现两位数增长。集团销售额增长14%，达37.3亿欧元。得益于通胀压力之下商品成本的改善以及稳定可靠的供应，调整后息税折旧及摊销前利润（EBITDA）增长19%，达8.02亿欧元。公司在2023财年做了95项许可交易（licensing deals）来促进业务纵深。2023年仿制药业务部门同比增加6%业绩，达15亿欧元。贡献业绩的产品有抗凝药物阿哌沙班、糖尿病药物西格列汀、止痛领域的他喷他多、用于移植患者的他克莫司，以及用于逆转肌肉松弛剂效果的舒更葡糖钠。新特药领域在2023年增长25%，增速为几大业务之最；目前为7.49亿欧元。产品包括多款生物类似药（biosimilar）（雷珠单抗、阿达木单抗、贝伐珠单抗、特立帕肽）。Uzpruvo（乌司奴单抗，Ustekinumab）的生物类似药即将上市，目前已经获批，等待欧洲市场原研药物专利过期。2023年上半年，史达德在药品可及性方面取得重大进展。美国食品药品监督管理局批准（FDA）从史达德位于德国尤特森的一家工厂向美国出口重组人红细胞生成素（EPO）。欧盟也几近同时确认位于越南绥和的新工厂符合要求严格的欧洲《药品生产质量管理规范》（GMP）标准，这为向欧洲出口提供了持续可靠的供应保障。与此同时，位于罗马尼亚图尔达供应链中心建设进展顺利；该中心投资超过5000万欧元，将大幅提升史达德在欧洲的供应链网络能力。在帕金森疾病（PD）领域，史达德的Lecigon pump成功结合三种经过验证的活性药物成分（levodopa + carbidopa + entacapone），用于治疗晚期帕金森病。该药品近期已在保加利亚、爱尔兰、西班牙和瑞士等更多国家上市，已有超千名患者使用；本品最早由LobSor Pharmaceuticals AB开发，相关专利WO-2016036308。药融云数据www.pharnexcloud.com；改良新药新复方在肾脏病学领域，欧盟批准的首个用于治疗罕见、慢性和致残性肾病IgA肾病的药物Kinpeygo（其他商品名Nefecon/Tarpeyo，4mg布地奈德靶向迟释胶囊）正在惠及更多患者。药融云数据www.pharnexcloud.com显示：Kinpeygo/Nefecon/Tarpeyo采用肠溶包衣，Nefecon/Tarpeyo这种改良新药的新剂型，可将布地奈德特异性递送至回肠的派尔集合淋巴结（负责产生分泌性免疫球蛋白A）处。胶囊溶解后，三层包衣微丸持续稳定释放布地奈德，高浓度覆盖整个靶区域。本品首创的瑞典公司Calliditas成立于2004年，产品最早购买权益于瑞典乌普萨拉大学（Uppsala University）两位教授那里。（中国等市场，云顶新耀持有相关权益，IgA肾病亟需新药：布地奈德改良新药美国加速获批）在2022年第4季度首次成为德国市场第一大OTC供应商。2020年从葛兰素史克（GSK）手中收购15个在欧销售的药品与保健品牌，2023年从赛诺菲收购多个欧洲国家的知名消费者健康品牌(Antistax、Lomudal、Omnivit和Opticrom滴眼液等)，构建多元化营养矩阵。1996年首度进入中国大陆。2021年，史达德在上海设立大中华区总部，显示出对中国大陆市场的高度重视。2024年5月28日，再来一单交易！来自中国的百奥泰生物制药股份有限公司（上交所代码：688177）与STADA Arzneimittel AG就BAT2506（一款参照欣普尼®戈利木单抗开发的生物类似药）签署授权许可及商业化协议，STADA将拥有BAT2506在欧盟、英国、瑞士以及其他部分欧洲国家市场的独占的商业化权益。根据协议条款，百奥泰将负责BAT2506的研发、生产以及商业化供应，STADA将负责BAT2506在欧盟、英国、瑞士以及其他部分欧洲国家市场的商业化。在达到相应的里程碑事件后，百奥泰可获得首付款加上里程碑款总金额最高至1.575亿美元，以及净销售额的两位数百分比作为收入分成。附，分享：此前3月底，公开了STADA集团年报。发送仿制药（请正确复制）至下方药融圈微信公众号后台可获得原文件。仅供学习交流分享！参考：NMPA/CDE；药融云数据www.pharnexcloud.com；FDA/EMA/PMDA；相关公司公开披露；https://www.stada.com/;2023年财报，https://www.stada.com/media/8669/fy2023-annual-report-stada.pdf；https://www.stadabeijing.com/；Pharmaceutical Executive, Pharma 50 Insight: The Accelerating Growth of Specialty Markets. Waseem Noor and Michael Kleinrock, 2022. https://www.pharmexec.com/；史达德2023年销售额和利润继续保持两位数增长，https://mp.weixin.qq.com/s/32m0q02jGSjblg7tk7f_Ow；www.bio-thera.com；本稿中不再涵盖其俄罗斯业务，该业务由史达德在其前俄罗斯子公司（AO Nizhpharm、OOO Aqualor、Dialogfarma LLC和OOO Hemofarm）中的股权组成，这些股权已于2023年9月转让给史达德集团之外的另一家公司；等等。本文仅用于向医疗卫生专业人士提供科学信息，不代表平台立场，不作任何用药推荐活动推荐 8月 • NDC2024生物医药创新者峰会关键词：小分子，XDC，多肽及GLP-1热点话题，200+行业专家（点击下方图片查看详情）▼【关于药融圈】药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。

生物类似药专利到期引进/卖出

2024-05-22

·Pharmaceutical Technology

Alvotech and Dr Reddy’s partner to commercialise AVT03

Prolia and Xgeva are used to prevent skeletal-related events in adults with advanced cancers. Credit: Perfect Wave/ Shutterstock.com Alvotech has entered a collaboration with Dr Reddy’s Laboratories for the commercialisation of AVT03 in the US, Europe and the UK. AVT03 is a biosimilar candidate to the reference products Prolia and Xgeva (denosumab). Prolia and Xgeva are used to treat conditions including osteoporosis in postmenopausal women and to prevent skeletal-related events in adults with advanced cancers. The agreement will leverage Dr Reddy’s global commercial reach and Alvotech’s biosimilar development expertise. Alvotech will be tasked with the development and manufacturing of AVT03. See Also: S-95024 by Les Laboratoires Servier for Esophageal Squamous Cell Carcinoma (ESCC): Likelihood of Approval S-95024 by Les Laboratoires Servier for Non-Small Cell Lung Carcinoma: Likelihood of Approval Dr Reddy’s Laboratories will handle the registration and commercialisation of the product in the designated markets. The strategic collaboration comes with an undisclosed upfront payment to Alvotech, followed by regulatory and commercial milestone payments, as well as payments based on product sales. The commercialisation rights granted to Dr Reddy’s are solely for the US market and semi-exclusive for the UK and European markets. AVT03 is currently an investigational product and not approved by any regulatory agency. In January 2024 Alvotech reported positive top-line data from a pharmacokinetic study of AVT03 against Prolia in healthy adults. The study focused on the biosimilar’s pharmacokinetics, safety and tolerability. Further trials are in progress, including a confirmatory efficacy and safety study in patients and a pharmacokinetic study comparing AVT03 to Xgeva. Dr. Reddy’s CEO Erez Israeli stated: “Over the years, we have created a portfolio of biosimilar products, which are marketed in several emerging markets. Most recently, we launched bevacizumab, our first biosimilar in the UK. “This strategic collaboration augments our growing portfolio of biosimilar offerings, and progresses our biosimilar journey further into the highly regulated markets.” The latest development comes after Alvotech and Teva Pharmaceuticals obtained US Food and Drug Administration approval for Selarsdi (ustekinumab-aekn) via subcutaneous injection.

引进/卖出上市批准

100 项与乌司奴单抗生物类似药（Alvotech）相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
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研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
银屑病	欧盟	Alvotech	2024-01-10
银屑病	冰岛	Alvotech	2024-01-10
银屑病	列支敦士登	Alvotech	2024-01-10
银屑病	挪威	Alvotech	2024-01-10
银屑病关节炎	欧盟	STADA Arzneimittel AG	2024-01-05
银屑病关节炎	冰岛	STADA Arzneimittel AG	2024-01-05
银屑病关节炎	列支敦士登	STADA Arzneimittel AG	2024-01-05
银屑病关节炎	挪威	STADA Arzneimittel AG	2024-01-05
克罗恩病	欧盟	STADA Arzneimittel AG	2024-01-05
克罗恩病	冰岛	STADA Arzneimittel AG	2024-01-05
克罗恩病	列支敦士登	STADA Arzneimittel AG	2024-01-05
克罗恩病	挪威	STADA Arzneimittel AG	2024-01-05
活动性中度克罗恩病	欧盟	STADA Arzneimittel AG	2024-01-05
活动性中度克罗恩病	冰岛	STADA Arzneimittel AG	2024-01-05
活动性中度克罗恩病	列支敦士登	STADA Arzneimittel AG	2024-01-05
活动性中度克罗恩病	挪威	STADA Arzneimittel AG	2024-01-05
活动性重度克罗恩病	欧盟	STADA Arzneimittel AG	2024-01-05
活动性重度克罗恩病	冰岛	STADA Arzneimittel AG	2024-01-05
活动性重度克罗恩病	列支敦士登	STADA Arzneimittel AG	2024-01-05
活动性重度克罗恩病	挪威	STADA Arzneimittel AG	2024-01-05

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临床结果

适应症

分期

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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


NCT04930042 (AVT04-GL-301, FDA_CDER) 人工标引	临床3期	斑块状银屑病	2,069	Placebo (Ps STUDY 1 + Adult)	獵製鹽淵簾願膚鑰衊膚(蓋壓壓壓獵鏇範鑰繭壓) = 願齋顧願顧網遞憲衊淵廠鑰範積範顧範網構衊 (積網觸顧襯壓製簾鏇顧 ) 更多	积极	2024-04-16
				Ustekinumab 45 mg (Ps STUDY 1 + Adult)	獵製鹽淵簾願膚鑰衊膚(蓋壓壓壓獵鏇範鑰繭壓) = 餘淵齋構鑰襯繭選鹽鏇廠鑰範積範顧範網構衊 (積網觸顧襯壓製簾鏇顧 ) 更多
NCT04930042 (AVT04-GL-301, FDA_CDER) 人工标引	临床3期	银屑病关节炎	927	Ustekinumab 45 mg (PsA STUDY 1)	選鏇窪淵鏇艱積衊鬱鏇(廠願襯遞壓憲夢繭鏇糧) = 築齋艱構齋齋顧醖窪齋壓夢壓襯糧願餘膚範淵 (壓淵製鹹廠築衊網積範 ) 更多	积极	2024-04-16
				Ustekinumab90 mg (PsA STUDY 1)	選鏇窪淵鏇艱積衊鬱鏇(廠願襯遞壓憲夢繭鏇糧) = 鹹艱膚衊襯淵積鹽遞鹹壓夢壓襯糧願餘膚範淵 (壓淵製鹹廠築衊網積範 ) 更多
EADV 12023 \| EADV 22023	N/A	斑块状银屑病	581	AVT04	願襯觸齋淵廠艱壓膚網(鬱膚窪廠齋鬱積鑰願壓) = 齋鏇積積獵範築鹽齋夢製鬱醖顧簾齋鬱鏇製夢 (鹹簾窪齋衊醖構鹹夢鹹 )	积极	2023-10-11
				Reference Product Ustekinumab	願襯觸齋淵廠艱壓膚網(鬱膚窪廠齋鬱積鑰願壓) = 簾築簾醖蓋餘淵範艱製製鬱醖顧簾齋鬱鏇製夢 (鹹簾窪齋衊醖構鹹夢鹹 )
NCT04930042 (Pubmed)	临床3期	斑块状银屑病	581	AVT04	願齋繭遞衊衊壓顧獵廠(積憲製顧襯築齋壓衊網) = 鹹艱鑰憲遞構鑰窪壓鹹顧鏇壓鏇夢鏇艱顧選鬱 (鹹蓋鏇顧觸獵鹽構顧遞 )	积极	2023-07-12
				Reference product ustekinumab (Stelara®)	願齋繭遞衊衊壓顧獵廠(積憲製顧襯築齋壓衊網) = 淵蓋網鬱鑰選顧鹽鏇範顧鏇壓鏇夢鏇艱顧選鬱 (鹹蓋鏇顧觸獵鹽構顧遞 )
NCT04930042 (AAD2023)	临床3期	银屑病	581	AVT04	鹽繭齋觸鹹膚鹽醖鑰襯(鑰窪鏇衊繭憲醖壓壓襯) = 壓襯鹽鹽窪餘夢積蓋廠顧鬱鑰網鏇醖鹹夢餘鹹 (廠築簾醖蓋窪鬱糧築膚 ) 更多	-	2023-03-17
				Reference Ustekinumab	鹽繭齋觸鹹膚鹽醖鑰襯(鑰窪鏇衊繭憲醖壓壓襯) = 鏇繭積鹽糧網齋築繭獵顧鬱鑰網鏇醖鹹夢餘鹹 (廠築簾醖蓋窪鬱糧築膚 ) 更多