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更新于：2025-01-22

Darvadstrocel ( TiGenix)

更新于：2025-01-22

概要

概要

基本信息

药物类型

间充质干细胞疗法

别名

Darvadstrocel、CX601、Alofisel

+ [1]

靶点-

作用机制

细胞替代物

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

Takeda Pharmaceutical Co., Ltd.

TiGenix NV

+ [1]

非在研机构

Hospital Universitario La Paz

Takeda Canada, Inc.

最高研发阶段批准上市

首次获批日期

欧盟 (2018-03-23),

肛瘘

最高研发阶段(中国)-

特殊审评-

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关联

项与 Darvadstrocel ( TiGenix) 相关的临床试验

NCT05974280

/ RecruitingN/AIIT

Pilot Study on the Treatment of Anal Fistulas in Crohn's Disease Patients Using Alofisel Versus Fat Autologous Stem Cells

One of the newest and most innovative medicinal approaches is cell therapy. Several clinical trials and experimental investigations have looked into the feasibility of treating CD-related fistulas with stem cells.
The current indication for ALOFISEL® (active ingredient: Darvadstrocel) is the treatment of difficult perianal Crohn's fistulas that have not responded well to at least one conventional therapy or biotherapy.
This brand-new cell therapy medication is created using amplified allogeneic human adult mesenchymal stem cells from adipose tissue (ADSC). The supplier mandates that two patients be booked for a single dose of ALOFISEL® due to the medication's expensive price-roughly €54,000 for a single dose of 120 million-which cannot be stored once thawed.
Only one of the two patients receives therapy; the other serves as the backup patient. By doing this, another "back-up" patient who might receive no care at all is avoided.
An developing alternate approach to allogeneic ADSC injection for the treatment of complicated anal fistulas in CD is autologous fat injection. In recent years, autologous fat grafts have been the subject of in-depth research. They are popular because it is simple to get clinical samples (lipoaspirate, adipose tissue), and because there are a lot of ADSCs in adipose tissue. Additionally, ADSCs show strong immunomodulatory and regenerative capacities.
We would wish to compare the effectiveness of these two injection kinds on perianal fistulas as part of our care of CD.

开始日期2024-01-02

申办/合作机构

Nantes University Hospital

NCT05113095

/ RecruitingN/A

Postmarketing Surveillance Registry to Evaluate Safety and Efficacy of Darvadstrocel for the Treatment of Complex Perianal Fistulas in Crohn's Disease Patients (J-INSPIRE) (All-case Surveillance)

This study is a survey in Japan of Darvadstrocel injection used to treat Crohn's disease people with complicated anal fistula. The study sponsor will not be involved in how the participants are treated but will provide instructions on how the clinics will record what happens during the study.
The main aim of the study is to check for side effects related from Darvadstrocel injection and to check if Darvadstrocel injection improves symptoms of Crohn's disease. During the study, participants with Crohn's disease will take Darvadstrocel injection according to their clinic's standard practice. The study doctors will check for side effects from Darvadstrocel for 36 months.

开始日期2021-11-30

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

NCT04701411

/ Recruiting临床3期

A Phase 3, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of Darvadstrocel in the Treatment of Complex Perianal Fistula in Pediatric Subjects With Crohn's Disease Over a Period of 24 Weeks and an Extended Follow-up Period for a Total of up to 52 Weeks

A perianal fistula is an abnormal passageway that develops between the rectum and the skin near the anus. The fistula is considered complex if it branches into several openings or an abscess is also present.
The main aim of this study is to learn if complex perianal fistulas in children and teenagers close after treatment with darvadstrocel.
2 to 3 weeks before treatment with darvadstrocel, each participant will have surgery to clean the fistula and to drain any abscesses. On the day of treatment, each participant will have the fistula cleaned and will receive an injection of darvadstrocel near the fistula, under anesthetic.
For up to 1 year after treatment, participants will regularly visit the clinic for follow-up. The fistula will be examined and any side effects from the treatment will be recorded. Participants will have an MRI at one clinic visit (about 24 weeks after treatment).

开始日期2021-06-30

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

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100 项与 Darvadstrocel ( TiGenix) 相关的临床结果

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100 项与 Darvadstrocel ( TiGenix) 相关的转化医学

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100 项与 Darvadstrocel ( TiGenix) 相关的专利（医药）

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项与 Darvadstrocel ( TiGenix) 相关的文献（医药）

2024-11-01·Clinics and Research in Hepatology and Gastroenterology

Real-life effectiveness of allogeneic expanded adipose-derived mesenchymal stem cell therapy for perianal fistulizing refractory Crohn's disease

Article

作者: Altwegg, Romain ; Nancey, Stéphane ; Danion, Pauline ; Cotte, Eddy ; Boschetti, Gilles ; Charlois, Anne Laure ; Gay, Claire ; Alonso-Gomez, Maria ; Malezieux, Emilie

BACKGROUND:

Real life data about the long-term efficacy of darvadstrocel for treating perianal fistulas in Crohn's disease (CD) remain scarce.

AIM:

To report the effectiveness and safety of darvadstrocel therapy to close perianal fistula in a real-life cohort of CD patients.

METHODS:

All patients with CD suffering complex draining perianal fistulas who consecutively underwent administration of a single local injection of darvadstrocel at two centres were followed up and evaluated. The primary endpoint was clinical remission (closure of all external openings with no discharge at pressure) at week 24. Combined remission (defined as clinically plus MRI-assessed fistula closure) were also assessed at week 24 and 52.

RESULTS:

A total of 36 CD patients (19 Male, mean age 38.5 years) were included with a median follow up of 16 months. Clinical remission was achieved in 17 out of 36 patients (47.2 %) and combined remission in 15 out of 36 patients (41.6 %) at week 24. At week 52, clinical and combined remission was achieved in 17 out of 36 patients (47.2 %) and in 15 out of 33 evaluable patients (45.4 %), respectively.

CONCLUSION:

In this real-world setting, a successful response to darvadstrocel therapy based on clinical remission was reported in around half of the patients and combined remission including radiological assessment in more than 4 out of 10 patients.

2024-08-02·EXPERT OPINION ON BIOLOGICAL THERAPY

The potential for medical therapies to address fistulizing Crohn’s disease: a state-of-the-art review

Review

作者: Bessissow, Talat ; Lakatos, Peter L. ; Shehab, Mohammad ; De Marco, Davide

INTRODUCTION:

Crohn's disease (CD) is a chronic, relapsing immune mediated disease, which is one of the two major types of inflammatory bowel disease (IBD). Fistulizing CD poses a significant clinical challenge for physicians. Effective management of CD requires a multidisciplinary approach, involving a gastroenterologist and a GI surgeon while tailoring treatment to each patient's unique risk factors, clinical representations, and preferences.

AREAS COVERED:

This comprehensive review explores the intricacies of fistulizing CD including its manifestations, types, impact on quality of life, management strategies, and novel therapies under investigation.

EXPERT OPINION:

Antibiotics are often used as first-line therapy to treat symptoms. Biologics that selectively target TNF-α, such infliximab (IFX), have shown high efficacy in randomized controlled trials. However, more than 50% of patients lose response to IFX, prompting them to explore alternative strategies. Current options include adalimumab and certolizumab pegol combination therapies, as well as small-molecule drugs targeting Janus kinases such as Upadacitinib. Furthermore, a promising treatment for complex fistulas is mesenchymal stem cells such as Darvadstrocel (Alofisel), an allogeneic stem cell-based therapy. However, surgical interventions are necessary for complex cases or intra-abdominal complications. Setons and LIFT procedures are the most common surgical options.

2024-05-01·Wiener klinische Wochenschrift

Efficacy of cx601 (darvadstrocel) for the treatment of perianal fistulizing Crohn’s disease—A prospective nationwide multicenter cohort study

Article

作者: Riss, Stefan ; Harpain, Felix ; Czipin, Sascha ; Pramhas, Michael ; Scharitzer, Martina ; Dawoud, Christopher ; Stift, Anton ; Widmann, Kerstin Melanie

Summary:

Background:

The use of mesenchymal stem cells is considered a novel and promising therapeutic option for patients with perianal fistulizing Crohn’s disease; however, data on its clinical application remain scarce. This multicenter nationwide study aimed to assess the clinical efficacy of mesenchymal stem cells in closing complex anal fistulas.

Methods:

In this study 14 Crohn’s disease patients (3 males, 11 females) with complex anal fistulas treated in 3 tertiary hospitals in Austria were included between October 2018 and April 2021.Injection of 120 million allogeneic expanded adipose-derived mesenchymal stem cells (Cx601—darvadstrocel) was performed in each patient. Closure of the external fistula opening without secretion by external manual compression was defined as treatment success.

Results:

The median age of the patient population at the time of surgery was 32 years (range 26–53 years) with a median body mass index of 21.7 kg/m2 (range 16.7–26.6 kg/m2). Of the patients 12 (86%) received monoclonal antibodies (infliximab, adalimumab, ustekinumab, vedolizumab) at the time of surgery.The median number of complex fistulas was 1.4 (range 1–2), The median operative time was 20 min (range 6–50 min) with no perioperative complications.After a median follow-up of 92 weeks, we found successful fistula closure in 57.1% (n = 8) of treated patients. The perianal disease activity index did not improve significantly from initially 7 to a median of 6 after 52 weeks (p = 0.495).

Conclusion:

Darvadstrocel is a safe, minimally invasive surgical technique without significant perioperative complications. Clinical success can be expected in about half of the treated patients.

项与 Darvadstrocel ( TiGenix) 相关的新闻（医药）

2025-01-10

·Business Wire

Clinical and Commercial Developments in MSCs: 1,670+ Trials Highlight Versatile Applications and Emerging Opportunities - ResearchAndMarkets.com

DUBLIN--( BUSINESS WIRE )--The "Mesenchymal Stem Cells / Medicinal Signaling Cells (MSCs) - Advances & Applications, 2025" report has been added to ResearchAndMarkets.com's offering. MSCs are multipotent cells that have been referred to as mesenchymal stem cells, medicinal signaling cells, and mesenchymal stromal cells, reflecting their versatility and diverse applications. MSCs can differentiate into a variety of cell types, such as osteoblasts, chondrocytes, myocytes, and adipocytes. Their unique ability to secrete factors that promote tissue repair and modulate their microenvironment with anti-inflammatory and anti-fibrotic effects makes them essential in regenerative medicine. Furthermore, their immuno-evasive properties make MSCs particularly suitable for allogenic transplantation. MSCs serve as vital raw materials across numerous industries, including regenerative medicine, cosmeceuticals, and cultured meat production. Key applications include: Cell-based therapies for musculoskeletal diseases, spinal injuries, and cardiovascular conditions. Engineered tissues and organs, such as skin, bone, blood vessels, and liver. Cell-derived products, such as exosomes and growth factors, utilized in cosmetics and skincare. Cultured meat production, leveraging MSCs' role in muscle development and their ability to differentiate into muscle and fat cells. Globally, 12 MSC-based therapies have been approved for various indications, with the majority concentrated in South Korea, Japan, and the EU. Specifically, the Republic of Korea has approved five products: Queencell from Anterogen, Cellgram AMI from Pharmicell, Cupistem from Anterogen, Cartistem from Medipost, and NeuroNataR from Corestem. Japan has approved two products: Temcell HS from JCR Pharmaceuticals and Stemirac from Nipro Corporation. The EMA in Europe has approved two products: Holoclar from Chiesi Farmaceutici and Alofisel from TiGenix/Takeda. India has approved one product: Stempeucel from Stempeutics. Iran has approved one product: MesestroCell developed by Cell Tech Pharmed. Finally, Australia has approved one product: Remestemcel-L from Mesoblast. Despite this progress, no MSC-based therapeutic have yet received U.S. FDA approval, although the FDA is actively reviewing Mesoblast's Remestemcel-L. The cosmeceutical market is also rapidly adopting MSC-derived products, particularly exosomes, to leverage their anti-aging and regenerative properties, with companies like L'Oreal and Johnson & Johnson investing heavily in this space. Similarly, cultured meat companies are utilizing MSCs for producing muscle and fat cells, enhancing taste and texture. Groundbreaking approvals, such as lab-grown chicken by Upside Foods and Good Meat, have paved the way for further growth in this industry. MSC-based gene editing is expanding, enabling the overexpression of antitumor genes and therapeutic factors. Researchers are also exploring the use of MSCs in 3D printing and engineered organ production, with breakthroughs anticipated in the next decade. Importantly, companies like Cynata Therapeutics are pioneering iPSC-derived MSC production technologies, enabling large-scale therapeutic development. Today there are at least eight companies who are involved with the development of iPSC-derived MSCs therapeutics (iMSCs), including Cynata Therapeutics, Eterna Therapeutics, Implant Therapeutics, Bone Therapeutics, Brooklyn ImmunoTherapeutics, Fujifilm CDI, Citius Pharmaceuticals, and Kiji Therapeutics. There are also over 1,670 clinical trials involving MSCs are registered on ClinicalTrials.gov. Nearly 75% of these clinical studies are using MSCs for the development of regenerative medicine (RM) products. Approximately 14% of the studies are using MSCs for disease modeling. The remaining 11% of the studies are using MSCs for drug discovery and cytotoxicity testing applications. Challenges in these trials include maintaining MSC phenotype and functionality during expansion. However, ongoing advancements suggest a promising future, with projections for at least 50 globally approved MSC-based products by 2040, averaging 3-4 new approvals annually. Key Players in MSC Research Products The demand for MSC-based research products has surged in recent years, with major suppliers expanding their portfolios. Companies like RoosterBio have increased the access to quality MSCs through supply chain industrialization, standardized cell bank product forms, and fit-for-purpose cGMP-compatible cells and media systems. Other leading MSC research product suppliers include PromoCell, Lonza, Thermo Fisher Scientific, STEMCELL Technologies, Miltenyi Biotec, Bio-Techne (R&D Systems), ScienCell Research Laboratories, and the ATCC. Challenges and Opportunities While MSC commercialization faces hurdles-such as scalability and regulatory approval-opportunities abound. The market for MSC-based products is poised for notable growth across the research, therapeutic, cosmetic, and food industries. Within this rapidly changing landscape, having a thorough understanding of the competition is essential. This global strategic report presents rates of MSC clinical trials, scientific publications, patents, funding events, and collaborations. It presents the pipeline for MSC-based therapeutics, identifies market opportunities and threats, and explores future directions and emerging applications. It reveals innovative MSC products, services, and technologies offered by 125 leading competitors. Finally, it presents detailed market size figures for the global MSC market, segmented by geography and business segment with future forecasts through 2031. Key Topics Covered: MESENCHYMAL STEM CELLS (MSCs): AN OVERVIEW Stabilization of hMSCs as a Technology The Impact of MSCs on Regenerative Medicine Timeline of MSC Nomenclature Sources of MSCs Cell Surface Markers in MSCs In vitro Differentiation Potentials of MSCs Soluble Factors Secreted by MSCs Stemness Genes Present in MSCs Types of MSCs and their Biomedical Applications Genes that are Pivotal for MSC's Properties MSC-BASED CLINICAL TRIAL LANDSCAPE MSC-Based Clinical Studies by Geography Sources of MSCs used in Current Clinical Trials Share of Autologous & Allogeneic MSCs Clinical Trials MSC-Based Clinical Trials by Disease Indication MSC-Based Clinical Trials by Phase of Study Select MSC-Based Clinical Trials MESENCHYMAL STEM CELLS (MSCS): PATENT LANDSCAPE MSC Patent Publications by Jurisdiction MSC Patent Applicants MSC Patent Inventors MSC Patent Owners Legal Status of MSC Patent Applications MSC-Derived Exosome Patents Patents for iPSC-Derived MSCs MSC Patents by Therapy Type PUBLISHED SCIENTIFIC PAPERS ON MSCS MSC MANUFACTURING PLATFORMS: AN OVERVIEW Methods of Isolations of MSCs Cell Expansion: Conventional Cultures to Bioreactors Downstream Processing of MSCs Autologous & Allogeneic MSC Manufacturing: A Comparison MSC Manufacturing Economics in Small Scale Large Scale Manufacturing of MSCs CELL & GENE THERAPY CONTRACT MANUFACTURING Staff Shortage Need for Automation Capacity Constraints CDMO Platforms with Greater Potentials CMOs/CDMOs Geographic Distribution of Manufacturing Facilities Continued Rise of Outsourcing Major CDMOs in the U.S Major Cell & Gene Therapy CDMOs in Europe U.K.'s Domination in European Contract Manufacturing BIOENGINEERING SOLUTIONS TO BOOST MSC'S FUNCTIONS Small Molecule Priming of MSCs Particle Engineering of MSCs Genetic Engineering of MSCs Examples of Bioengineered MSCs to Produce Anticancer Therapeutics Engineered MSCs for Neurological Conditions Engineered MSCs for Cardiovascular Diseases Engineered MSCs for Lung Injury Engineered MSCs for Diabetes Bioengineering Approaches to Improve MSC Administration MAJOR DISEASES ADDRESSED BY MSCS Studies Using MSCs for Autoimmune Diseases Studies using MSCs for Cardiovascular Diseases Studies using MSCs for Neurodegenerative Diseases Studies using MSCs for Bone & Cartilage Diseases Studies using MSCs in GvHD Studies using MSCs in Crohn's Disease Studies using MSCs in Type 1 Diabetes Studies using MSCs in Systemic Lupus Erythematosus (SLE) Studies using MSCs in Parkinson's Disease Studies using MSCs in Alzheimer's Disease Studies using MSCs in Kidney Failure Studies using MSCs in Spinal Cord Injury Studies using MSCs for Wound Healing RECENT COLLABORATIONS IN MSC SECTOR, 2020-2024 Collaboration between BioSolution Designs & RoosterBio Collaboration between CytoMed Therapeutics, Ltd. & Sengkang General Hospital Collaboration between REPROCELL & Histocell Collaboration between FUJIFILM Dyosynth & RoosterBio RoosterBio's Collaboration with AGC Biologics RoosterBio's Partnership with ShiftBio RoosterBio's Partnership with Univercells Technologies Collaboration between Cynata & Fujifilm Collaboration between American CryoStem Corp. & BioTherapeutic Lab Corp. RoosterBio's Collaboration with Sartorius Collaboration between American CryoStem and CRADA RoosterBio's Collaboration with Sartorius Korea Biotech Collaboration between Catalent & BrainStorm Collaboration between Cipla & Stempeutics Aethlon's Collaboration with University of Pittsburgh RoosterBio's Collaboration with Senti Biosciences MSC-BASED PRODUCTS IN THE MARKET Approved MSC Therapies Queencell Cellgram AMI Cupistem Cartistem NeuroNataR Holoclar Remestemcel-L Temcell HS Stempeucel Alifosel MesestroCell Stemirac Marketed Biomaterial Carrier-Based MSCs & MSC Progenitors Osteocel AlloStem Grafix Cellentra VCBM Trinity ELITE Map3 BIO4 Trinity Evolution Carticel Chondron DeNovo NT Chondrocelect Ossron JACC MACI Ortho-ACI Ossgrow Cartigrow Topical Cosmetic Products Containing MSCs/MSC-Derived Exosomes MARKET ANALYSIS Market Size for MSC Therapies Global Demand for Mesenchymal Stem Cells (MSCs) COMPANY PROFILES Advancells Aegle Therapeutics AGC Biologics AlloSource, Inc. Ambulero American CryoStem Corporation American Type Culture Collection (ATCC) Amniotics Andelyn Biosciences Anemocyte S.r.l Anterogen, Co., Ltd. Avid Bioservices, Inc. Bacthera Baylx, Inc BioCardia BioCentriq BioEden, Inc Bioinova s.r.o BioRestorative Therapies Bioscience Institute S.p.A Blue Horizon International Boehringer Ingelheim BioXellence Bonus Biogroup, Ltd BrainStorm Cell Therapeutics, Inc. Catalent CCRM Cell2Cure ApS Cell Care Therapeutics Cellcolabs CELLeBRAIN Cellipont Bioservices Celprogen, Inc CellProthera CellResearch Corporation, Pte, Ltd. Cell Surgical Network (CSN) Celltex Therapeutics Corporation CellTherapies Cellular Biomedicine Group Charless River Laboratories CHIESI Farmaceutici S.p.A Citius Pharmaceuticals, Inc CorestemChemon, Inc. Creative Bioarray Creative Medical Technology Holdings, Inc Curia Global, Inc Cynata Therapeutics, Ltd. Cytovance Biologics Defined Bioscience, Inc Direct Biologics eQcell, Inc. Excellos Exosla Therapeutics EXOSOMEplus Exothera Fujifilm Diosynth Biotechnologies Future Cell Japan, Co., Ltd. Genezen GenScript Biotech Corporation Hope Biosciences, Implant Therapeutics, Inc INCELL Corporation InGeneron Invitrx Therapeutics Japan Tissue Engineering, Co., Ltd. (J-TEC) JCR Pharmaceuticals, Co., Ltd. Jointechlabs Kangstem Biotech, Co., Ltd. Kimera Labs LifeCell Longeveron Lonza Group, Ltd Lorem Cytori USA, Inc. MEDPOST Mesoblast, Ltd Millipore Sigma NecstGen NextCell NIPRO Corporation Novadip Biosciences Novus Biologicals NuVasive OCT Therapies & Research Pvt., Ltd OmniaBio, Inc Orthocell, Ltd Orthofix Medical, Inc. Ossium Health Personal Cell Sciences Corporation Personalized Stem Cells, Inc. Pfizer CentreOne Pluri Biotech, Ltd. Porton Advanced Prometheus Life Technologies PromoCell PuREC, Co., Ltd Regrow Biosciences Reliance Life Sciences Remedy Cell Rentschler Biopharma REPROCELL USA Resilence RESTEM RHEACELL Richter-HELM RoosterBio RTI Surgical RoslinCT Samsung Biologics San Bio, Co., Ltd. Smith & Nephew, Inc StemBioSys, Inc STEMCELL Technologies, Inc Stemedica Cell Technologies, Inc Stemmatters StemMedical Stempeutics Research Pvt., Ltd StromaBio TaiwanBio Therapeutics, Co., Ltd Takeda Pharmaceutical, Co., Ltd Tempo Bioscience ThermoFisher Scientific Vericel Corporation Wuxi App Tec Xintela For more information about this report visit https://www.researchandmarkets.com/r/upnyhu About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

上市批准临床研究

2024-12-18

·同写意

干细胞疗法，“永生”之舟？

生老病死是任何人都无法逃脱的自然法则。无数帝王为了实现永生的夙愿，不惜炼丹试药，但最终都只不过是过眼云烟。尽管目前的科技水平无法使人类达到长生不老的地步，但科学的进步促使人类寿命不断增加也是不争的事实。如果科技带来的延寿速度快于自然衰老的速度，那么就相当于达到了“生命逃逸速度”，也就是说人类将在不断延寿的过程中达到永生。一场关于“永生”的全球竞赛，其实早已拉开序幕。 1 重建生命的神奇“魔法” 干细胞是一类具有自我复制和多向分化潜能的细胞群体，被医学界称为“万用细胞”，主要来源于脐带血、骨髓、外周血、胚胎及牙髓等，在特定的条件或者特定的信号诱导下能够分化成多种功能细胞或组织器官。追根溯源，最早提出“干细胞”一词的是德国生物学家Ernst Haeckel，他于1868年首次用其来描述受精卵产生生物体所有细胞的特性。基于此，医学界逐渐开始尝试利用干细胞进行治疗，也就是利用干细胞或干细胞衍生的细胞，以特殊技术移植到体内替代或分泌活性因子修复病人受损的细胞、组织或器官。尽管人类很早就进行了尝试，但直至90年后才真正地取得了实质性的进展。1958年，法国肿瘤学家George Mathe首次进行了一次异体干细胞移植，使用骨髓移植治疗了6名意外暴露于放射性物质的研究人员，其中有5例获得成功。正是这一里程碑式的案例，让业界看到了干细胞疗法的真正价值。十年后的1968年，Gatti等人成功地为一位重症联合免疫缺陷患儿实施了HLA相合的同胞间骨髓移植，自此之后干细胞疗法便开始驶入发展快车道。然而，干细胞疗法一直因伦理问题而受到大众的质疑。一些人认为人类胚胎从受精那一刻起就拥有与成人相同的权利，因此使用人类胚胎进行研究是不道德的。直到2007年，日本科学家山中伸弥使用人皮肤细胞经重编程获得了具有分化潜能的诱导多能干细胞（iPSCs），该研究一定程度缓和了胚胎干细胞研究涉及的宗教、伦理问题，并于2012年获得了诺贝尔医学或生理学奖。由于干细胞种类繁多，与之对应的治疗机理也各不相同，大体可以分为以下三类： ◆ 体内分化，体内治疗在体外进行简单分离后，将干细胞直接移植入体内修复损伤部位。临床上主要用于放/化疗之后补充造血干细胞，进而重塑整个造血系统和免疫系统。 ◆ 体外分化，替代治疗通过体外大量扩增并诱导分化，将干细胞变成特定的功能细胞，再移植入体内，对损伤部位修复。最具代表性的是多能干细胞治疗，如利用诱导多能干细胞治疗视网膜黄斑变性、帕森病、心脏衰竭、脊髓损伤等疾病。此外，这一原理还应用在很多干细胞衍生技术，如3D细胞打印技术、3D培养技术，微组织技术、类器官技术等。图：干细胞疗法简单示意图 ◆ 分泌效应，信号引导大部分干细胞进入体内并不会分化成损伤部位的细胞，而是通过分泌活性因（包括细胞因子、外囊泡等信号分子），调节免疫或促进组织修复。例如，间充质干细胞通过静脉输注后，一开始绝大部分都会滞留在肺部，之后部分细胞迁移至其他组织器官以及损伤部位，在过程中释放各种活性因子（包括细胞因子，外囊泡等）。以结果而论，干细胞疗法无疑是成功的，为一些传统医学难以治愈的疑难病症带来了新的曙光。如神经系统疾病的帕金森病和阿尔茨海默病，就有希望通过干细胞分化为神经细胞，替代受损的神经元，有望改善患者的认知和运动功能；再比如心血管疾病领域，干细胞能够分化为心肌细胞，修复受损的心肌组织；在糖尿病治疗中，干细胞可分化为胰岛细胞，分泌胰岛素，为1型糖尿病患者提供一种潜在的根治方法，同时也有助于改善2型糖尿病患者的胰岛功能。干细胞，相当于对人体细胞的一次重构，如果将人体的细胞全部替换，那是否就相当于一次新生呢？ 2 全球研发热潮基于干细胞疗法强大的应用潜力，这一赛道的关注度也在持续升高。目前，根据发育阶段来源可将干细胞分为胚胎干细胞、成体干细胞以及iPS干细胞三类。同时，根据分化潜能的大小，干细胞又可分为全能干细胞、多能干细胞和单能干细胞三类。图：干细胞疗法分类，来源：民生证券全能干细胞（如胚胎干细胞）可分化成为机体的任何细胞，分化潜力最大，无疑是人体最佳的修复材料。然而，却受限于潜在的胚胎瘤风险和社会伦理问题。因此，多能干细胞疗法是当下干细胞研发的重点。虽然多能干细胞并没有全能干细胞那样强大的分化能力，但也具有多向分化潜能，尤其是间充质干细胞更是现阶段科学研究与临床应用最多的干细胞。据不完全统计，目前全球已上市的干细胞疗法药物共25款，其中有8款属于间充质干细胞疗法，11款属于造血干细胞疗法，其中美国上市的药品数量最多，共10款。在我国，造血干细胞被视为器官移植监管，而不是作为药物监管，因此我们寻找这一原则，并不将造血干细胞疗法计算在内。在研产品方面，根据智慧芽数据，截至2023年2月底，全球正在开发的干细胞疗法药物1041款，全球开展的临床试验1811项，其中临床前246项，临床I期95项，临床II期76项，临床III期26项。药物类型上，间充质干细胞疗法占比高达60%，造血干细胞疗法占比11.5%，诱导多能干细胞疗法占比1.9%，神经干细胞疗法占比1.9%，其余干细胞疗法占比24.7%。从覆盖的适应症方面，目前的临床研究涉及适应症包括自身免疫性疾病（类风湿关节炎、强直性脊柱炎、银屑病、移植物抗宿主病）、代谢性疾病（糖尿病足溃疡）、骨关节病（骨关节炎）、呼吸系统疾病（肺纤维化、肺损伤）、消化系统疾病（肝衰竭、克罗恩病）、心脑血管疾病（脑卒中）等病种，并仍在不断扩展边界。从地区分布来看，美国拥有世界顶尖水平的高校、研究机构及医疗机构，是全球干细胞医疗第一大技术来源国，专利申请量占全球干细胞医疗专利总申请量的28%，一直占据着主导地位。同时，由于美国的私人医疗市场发达，为干细胞疗法的商业化应用提供了广阔的空间，全球获批的脐血造血干细胞产品中，80％来自美国。不过，由于严格的FDA审核要求，至今还没有批准任何间充质干细胞疗法上市。相反欧洲、日本、韩国等国家和地区对于新兴医疗技术和治疗方法秉持着开放的态度，越来越多的干细胞产品成功上市。今年7月，Mesoblast公司向FDA重新提交了Ryoncil的上市申请，用于治疗类固醇难治性急性移植物抗宿主病（SR-aGVHD）的儿童，该申请的PDUFA日期为2025年1月7日。Ryoncil是一种间充质干细胞，通过抑制T细胞增殖，和下调促炎细胞因子和干扰素的产生，来调节T细胞介导的炎症反应。如果Ryoncil顺利获批，那么将成为美国第一类获批的干细胞创新疗法。美国市场之外，韩国已经批准5款间充质干细胞疗法，包括Queencell、Cupistem等；日本作为iPSC的开创者也紧随其后，批准了3款间充质干细胞疗法，包括Temcell、Stemirac等；欧洲也批准了Holoclar和Alofisel两款干细胞药物。以全球干细胞产业发展速度看，其并没有遵循创新药FDA“唯我独尊”的趋势，从原本美国一家独大的局面开始朝着其他国家和地区均衡化的方向发展。这也从侧面表明，全球各国对于干细胞疗法的重视程度。 3 下一个必争之地？如果说未来有什么产业会如同“芯片”一样成为大国博弈的焦点，干细胞疗法在内的生物技术绝对占有一席之地。干细胞曾经连续两次被《科学》（Science）杂志列为世界十大科学问题之首，干细胞研究还曾在2007年和2011年获得诺贝尔生理学和医学奖。通过研究干细胞不仅能够攻克各种疾病、延缓衰老、增强免疫的潜力，而且还有助于深入了解生命的起源、发育以及疾病的发生发展过程，从而推动基础医学的发展，促进医学技术的创新。同时，干细胞产业涉及生物医药、医疗器械、健康管理等多个领域，是一个具有高附加值的产业。发展干细胞产业可以带动相关产业的发展，提升国家的产业竞争力，促进经济的可持续发展。因此，干细胞疗法作为体现国家意志、服务国家需求、代表国家科技创新最高水平的战略科技力量，越来越受到全球各个大国的重视。美国为了维持其在干细胞疗法领域的优势地位，曾在2022年9月，签署《关于促进生物技术和生物制造创新以建立可持续、安全和有保障的美国生物经济的行政命令》，旨在保护核心技术，号召生物制造回流美国本土，以减少对外部的依赖。特朗普的胜选，更是为干细胞疗法在美国的发展打下一剂强心针。2018年，特朗普签署了《尝试权法案》，该法案旨在帮助绝症患者获得未经美国 FDA 完全批准的药物治疗，其中也包括一些处于试验阶段的干细胞疗法。在其首个总统任期内，特朗普就通过国会演讲等多种途径表达了对干细胞治疗的支持与认可。他还强调，FDA漫长且繁琐的审批流程会阻碍许多研究成果应用到真正有需要的领域。如今特朗普再次上台，或将进一步提升干细胞疗法的战略地位，为其设置更为宽松的政策环境，同时可能继续强化自身在医院产业的霸主地位。我国对干细胞疗法也高度重视。早在2016年，就已经把重点发展 “干细胞与再生医学” 纳入《“健康中国 2030”规划纲要》之中。不仅如此，在《十四五规划》里也清晰地将免疫细胞治疗、干细胞治疗、基因治疗产品等列入了规划内容。从科研资金支持上看，2016年—2022年，中央财政连续多年拨款总计近40亿元，支持了众多干细胞研究项目，涉及干细胞的基础研究、临床应用研究等多个方面，推动了干细胞疗法的科研进展。在监管制度层面，为了激励干细胞产业发展，我国干细胞政策实行了“双轨制”，直接对标美国相关制度。在这种模式下，干细胞既能够以医疗技术的形式申报备案，也可以当作药品来申请上市，这大大加快了干细胞临床转化的速度。政策和市场的双向推动下，近年来，我国干细胞研究已跃居世界前列，在该领域论文发表数量及专利申请量已连续5年位居世界第二，干细胞备案项目和干细胞IND注册受理项目数量成倍增长，通过新药注册申报途径研发的干细胞临床管线持续增加。截至2023年底，我国已有106款干细胞药物的临床试验申请获得CDE受理，其中79款为默认许可。2024年8月底，北京药监局核发了全国首张干细胞药物的《药品生产许可证》，干细胞疗法迈出了从研发到生产的关键一步。干细胞疗法正站在时代的风口浪尖，它承载着人类对健康和生命延续的无限憧憬。在全球竞争与合作的大舞台上，各国都在这片充满希望的领域里奋勇前行。无论是美国的战略保护与推进，还是中国的积极投入与发展，都预示着干细胞疗法将在未来全球生物医药版图中占据关键地位。同写意媒体矩阵，欢迎关注↓↓↓

细胞疗法

2024-12-16

·PipelineReview

Takeda Provides an Update on Alofisel® (darvadstrocel)

OSAKA, Japan and CAMBRIDGE, MA, USA I December 13, 2024 I Takeda ( TSE:4502/NYSE:TAK ) today announced that the company is working with the European Medicines Agency (EMA) to voluntarily withdraw the marketing authorization of Alofisel® (darvadstrocel), a treatment for complex perianal fistulas in patients with Crohn’s disease, in the European Union (EU). Alofisel is an allogeneic stem cell therapy that is approved in the EU for the treatment of complex perianal fistulas in adult patients with non-active/mildly active luminal Crohn’s disease, when fistulas have shown an inadequate response to at least one conventional or biologic therapy. 1 Alofisel should be used only after conditioning of the fistulas. The initial authorization of Alofisel in the EU was based on results from the Phase 3 ADMIRE-CD placebo-controlled registrational study. 1 Given the small population size (n = 212) and modest benefit observed in the ADMIRE-CD study (a difference of 15.8% between the modified intention-to-treat population versus placebo at 24 weeks), Takeda agreed to provide results from ADMIRE-CD II, a study that was underway, to confirm Alofisel’s efficacy. 1-3 In October 2023, Takeda communicated ADMIRE-CD II , a randomized placebo-controlled study of 568 patients with complex CPF, did not meet its primary endpoint of combined remission at 24 weeks. 3-5 Additional results, which were presented at the European Crohn’s and Colitis Organisation Congress 2024 in February, showed no statistical differences in any of the secondary endpoints. 5 The safety profile for Alofisel was consistent with prior studies as no new, emerging safety signals were identified. 2,4,5 “Guided by our values and the needs of patients living with this difficult-to-treat condition, we engaged the EMA, as well as health care professionals and others in the community, to review the totality of data and the role of our medicine,” said Ramona Sequeira, president, Global Portfolio Division, at Takeda. “Those valuable discussions indicated that despite the conflicting results across our data, the clinical benefit of Alofisel is no longer sufficient to justify its continued use in the EU. We recognize the difficulty of this outcome for patients and will work closely with the Crohn’s Perianal Fistulas (CPF) community during this transition.” In addition to the EU, Takeda is engaging health authorities about this outcome in countries where Alofisel is currently approved, keeping the best interest of patients at the forefront. Takeda is committed to continuing to share data from clinical and observational studies for the benefit of patients and the entire health care community, with the hope that these insights can contribute to scientific advancements in complex CPF. Health care professionals with medical-related questions about Alofisel should contact Takeda Medical Information at medinfoEMEA@takeda.com or medinfoAPAC@takeda.com . Patients should consult their treating health care professional if they have questions. About Alofisel® Alofisel® (darvadstrocel) is a dispersion for injection of expanded human allogeneic mesenchymal adult stem cells extracted from adipose tissue (expanded adipose stem cells – eASC) for the treatment of complex perianal fistulas in adult patients with non-active/mildly active luminal Crohn’s disease. Therapeutic Indications Alofisel is indicated for the treatment of complex perianal fistulas in adult patients with non-active/mildly active luminal Crohn’s disease, when fistulas have shown an inadequate response to at least one conventional or biologic therapy. Alofisel should be used only after conditioning of the fistulas. Important Safety Information Contraindications Hypersensitivity to the active substance, bovine serum or to any of the excipients. Special warnings and special precautions for use Alofisel may contain trace amounts of either gentamicin or benzylpenicillin and streptomycin. This should be considered in patients with known hypersensitivity to these classes of antibiotics. Local anaesthesia is not recommended due to the unknown effect of local anaesthetics on the injected cells. The injection of any substance other than sodium chloride 9 mg/mL (0.9%) solution (e.g. hydrogen peroxide, methylene blue, iodine solutions or hypertonic glucose solutions) through the fistula tracts is not allowed before, during, or after the injection of Alofisel as these may compromise the viability of the cells. Alofisel must not be administered using a needle thinner than 22G. Thinner gauge needles can cause cell disruption during injection and may compromise cell viability and, therefore, may affect efficacy of treatment. As Alofisel is a living stem cell therapy it cannot be sterilised, a risk of transmission of infectious agents exists, although the risk is considered to be low and controlled in the manufacturing process. Healthcare professionals administering darvadstrocel must, therefore, monitor patients for signs and symptoms of infections after treatment and treat appropriately, if needed. Alofisel should only be administered by specialist physicians experienced in the diagnosis and treatment of conditions for which darvadstrocel is indicated. Patients treated with Alofisel must not donate blood, organs, tissues and cells for transplantation. The traceability requirements of cell-based therapy medicinal products must apply. Fertility, Pregnancy & Lactation No data is available from the use of darvadstrocel in pregnant women. Darvadstrocel is not recommended during pregnancy and in women of childbearing potential who are not using contraception. As a precautionary measure, darvadstrocel is not recommended for administration during breast-feeding. Undesirable effects Based on clinical trial and post-marketing data, the most commonly reported adverse drug reactions were anal abscess, proctalgia and anal fistula with the most commonly reported serious adverse drug reactions of anal abscess and anal fistula. Procedural pain is associated to conditioning reactions occurring up to seven days after the fistula preparation for treatment administration. For EU audiences, please see the Summary of Product Characteristics (SmPC) for Alofisel®. Please consult with your local regulatory agency for approved labeling in your country. Takeda in Gastroenterology Takeda is committed to meeting the very real needs of those living with gastrointestinal (GI) diseases. We believe that GI and liver diseases are life-disrupting conditions. Beyond a fundamental need for effective treatment options, we understand that improving patients’ lives also depends on their needs being recognized. With more than 35 years of experience in gastroenterology, Takeda has made significant strides in addressing patient needs with treatments for inflammatory bowel disease, eosinophilic esophagitis, acid-related diseases, short bowel syndrome and motility disorders. We are making significant strides toward closing the gap on new areas of unmet need. Together with researchers, patient groups and others, we are working to advance scientific research and clinical medicine in GI. About Takeda Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit www.takeda.com . References SOURCE: Takeda Pharmaceutical Co

临床结果临床3期上市批准细胞疗法

100 项与 Darvadstrocel ( TiGenix) 相关的药物交易

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研发状态

批准上市

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适应症	国家/地区	公司	日期
直肠瘘	瑞士	Takeda Pharmaceutical Co., Ltd.	2019-02-15
肛瘘	欧盟	Takeda Pharma A/S	2018-03-23
肛瘘	冰岛	Takeda Pharma A/S	2018-03-23
肛瘘	列支敦士登	Takeda Pharma A/S	2018-03-23
肛瘘	挪威	Takeda Pharma A/S	2018-03-23

未上市

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适应症	最高研发状态	国家/地区	公司	日期
克罗恩病引起的肛周瘘	临床3期	奥地利	Tigenix SAU	2012-07-01
克罗恩病引起的肛周瘘	临床3期	比利时	Tigenix SAU	2012-07-01
克罗恩病引起的肛周瘘	临床3期	法国	Tigenix SAU	2012-07-01
克罗恩病引起的肛周瘘	临床3期	德国	Tigenix SAU	2012-07-01
克罗恩病引起的肛周瘘	临床3期	以色列	Tigenix SAU	2012-07-01
克罗恩病引起的肛周瘘	临床3期	意大利	Tigenix SAU	2012-07-01
克罗恩病引起的肛周瘘	临床3期	荷兰	Tigenix SAU	2012-07-01
克罗恩病引起的肛周瘘	临床3期	西班牙	Tigenix SAU	2012-07-01
克罗恩病	临床3期	美国	Tigenix SAU	-
溃疡性结肠炎	临床2期	西班牙	Hospital Universitario La Paz	-

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临床结果

适应症

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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


NCT03279081 (ADMIRE-CD II \| ADMIRE-CD-II, CTgov)	临床3期	克罗恩病引起的肛周瘘	568	Placebo (Placebo)	餘鑰簾壓壓遞糧鏇網糧(淵憲夢窪齋壓鹽齋繭範) = 膚憲製襯製鑰襯構餘鹹衊憲製衊膚鬱醖範積構 (築構憲窪繭膚積網觸衊, 窪廠簾夢網獵製廠廠艱 ~ 鹹網襯夢構衊襯艱蓋齋) 更多	-	2024-09-19
				Cx601 (Cx601)	餘鑰簾壓壓遞糧鏇網糧(淵憲夢窪齋壓鹽齋繭範) = 膚觸夢膚鏇願鬱廠襯窪衊憲製衊膚鬱醖範積構 (築構憲窪繭膚積網觸衊, 夢顧遞鏇艱製構醖簾夢 ~ 獵蓋齋鏇蓋膚齋餘網鹽) 更多
DDW2024	N/A	克罗恩病引起的肛周瘘	-	Darvastrocel	簾廠蓋願簾蓋鏇壓構壓(膚願製窪憲夢選選淵鏇) = The Perianal Crohn's Disease Index was significantly lower 3, 6, and 12 months after application in the healed compared to failed group - 1 (0-9), 0 (0-8) and 0 (0-9) vs. 7 (1-13, 8 (0-12) and 6 (0-12), p<0.005 遞糧鹹夢壓壓艱淵獵積 (獵觸鬱選鹽襯構鏇遞鑰 )	-	2024-05-21
NCT05742100 (PRIME, Pubmed \| Dis Colon Rectum) 人工标引	N/A	克罗恩病引起的肛周瘘	73	Darvadstrocel	鏇築鑰齋襯鹽簾蓋鹹顧(廠醖製積鬱顧憲廠遞醖) = No serious adverse events were reported 糧遞範蓋糧餘餘鏇淵觸 (夢襯鏇繭廠選遞夢簾鑰 )	积极	2024-04-11
NCT03279081 (ADMIRE-CD II, Corporate Publications) 人工标引	临床3期	克罗恩病引起的肛周瘘	-	Alofisel	壓壓選鹹鬱醖獵糧糧襯(顧構齋憲鬱觸膚窪糧鏇) = did not meet its primary endpoint of combined remission at 24 weeks, based on topline data 窪襯獵襯衊淵繭淵憲獵 (壓製顧構齋鑰鹹鹽齋衊 ) 未达到	不佳	2023-10-17
				Placebo
NCT03706456 (Pubmed) 人工标引	临床3期	克罗恩病 \| 肛瘘	22	Darvadstrocel	廠壓糧糧範壓餘獵窪憲(艱廠憲夢簾齋範鑰繭範) = 網淵願齋壓蓋網窪顧觸鹹襯膚範鬱鬱積艱糧選 (膚網艱範淵鹹廠夢積願, 38.5 ~ 79.6) 更多	积极	2022-09-23
NCT01541579 (ADMIRE-CD, Pubmed \| Dis Colon Rectum)	临床3期	克罗恩病引起的肛周瘘	40	Darvadstrocel	構顧積艱憲餘鹹遞鏇顧(淵鏇積構網鑰簾窪衊繭) = Through Week 104, 7 treatment-emergent serious adverse events were reported, of which 4 occurred between Weeks 52 and 104 簾糧構鹹製壓觸範膚構 (遞範構範願顧鑰選壓齋 )	-	2021-12-07
				Control (saline solution)
NCT03706456 (CTgov)	临床3期	克罗恩病引起的肛周瘘	22	Darvadstrocel	選構餘醖夢壓顧構壓鹽(艱淵鑰壓淵築廠積築鏇) = 鹽糧夢醖壓構衊製餘壓襯積醖糧鏇願膚選製積 (醖蓋觸壓鏇鏇範遞齋襯, 艱膚鑰膚糧遞構憲觸壓 ~ 膚夢築齋壓廠糧艱憲襯) 更多	-	2021-10-07
UEGW2020	N/A	肛瘘	-	Darvadstrocel	齋鏇網簾網衊積網淵壓(淵艱簾淵窪壓窪蓋夢鹹) = One AESI in each group (DVS: benign tumor not product related and control: malignant tumor) was reported during the study period. 獵壓鏇願觸艱窪顧蓋鏇 (網壓鏇鑰膚獵觸選選鏇 ) 更多	-	2020-10-01
				Darvadstrocel (Control)
NCT01541579 (Pubmed \| Lancet) 人工标引	临床3期	克罗恩病 \| 肛瘘	212	Cx601	顧選繭衊繭選簾齋獵膚(鏇齋簾鹽鑰淵艱壓餘製) = 夢簾繭簾顧壓選壓夢憲膚衊夢衊窪衊製憲網夢 (衊築範齋選餘鏇廠憲廠 ) 更多	积极	2016-09-24
				Placebo	顧選繭衊繭選簾齋獵膚(鏇齋簾鹽鑰淵艱壓餘製) = 積醖築鹹積齋鑰繭膚鹽膚衊夢衊窪衊製憲網夢 (衊築範齋選餘鏇廠憲廠 ) 更多