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2024-01-01

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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项与 Darvadstrocel ( TiGenix) 相关的文献（医药）

2024-01-01·Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland

Mesenchymal stem cell therapy for Crohn's perianal fistula—a real‐world experience

Article

作者: White, Ian ; Naftali, Timna ; Wasserberg, Nir ; Yanai, Henit ; Slavin, Moran ; Dotan, Iris ; Avni, Irit ; Tovi, Shifra

Abstract:

Aim:

Remission rates of medically and surgically treated complex perianal fistulas in Crohn's disease are low. Recently, trials have demonstrated the potential for long‐term remission with local injection of allogeneic adipose‐derived mesenchymal stem cells (darvadstrocel). Our aim was to analyse outcomes from our real‐world experience with this new treatment.

Methods:

All patients with Crohn's disease suffering complex perianal fistulas who consecutively underwent administration of darvadstrocel at two centres were followed up and evaluated. Patients were assessed for clinical remission, response, failure, and any complications during follow‐up. The results of all patients with a minimum of 3 months’ follow‐up are presented.

Results:

Thirty‐three patients with Crohn's disease and complex perianal fistulas were included. Of these, 20 (61%) experienced clinical remission that was maintained for a mean follow‐up of 14 (3–32) months. A total of 24 of 33 (73%) experienced at least 3 months of clinical remission, with four later having recurrence (3–12 months). Among the remaining nine patients who did not experience clinical remission, two (6%) had partial remission (such as one of two fistulas closing), two (6%) showed signs of response but not remission, and five (15%) showed no signs of healing. The mean time to maintained clinical remission was 6 weeks (range 2 weeks to 6 months), and there were no severe adverse events.

Conclusion:

In this real‐world experience, treatment of Crohn's disease complex perianal fistulas with darvadstrocel had a 61% success rate for maintained clinical remission.

2023-12-01·Techniques in coloproctology

Deep remission improves the quality of life of patients with Crohn’s disease and anoperineal fistula treated with darvadstrocel: results of a French pilot study

Article

作者: Akaffou, M ; Haouari, M A ; Alam, A ; de Parades, V ; Spindler, L ; Pommaret, E ; Fathallah, N ; Fels, A ; Barré, A

BACKGROUND:

The injection of allogeneic adipose tissue-derived mesenchymal stem cells (MSC) into anal fistulas in patients with Crohn's disease has never been evaluated in "real-life" conditions in France.

METHODS:

We prospectively studied the first patients receiving MSC injections at our center and undergoing 12 months of follow-up. The primary endpoint was the clinical and radiological response rate. The secondary endpoints were symptomatic efficacy, safety, anal continence, quality of life (Crohn's anal fistula-quality of life scale, CAF-QoL), and predictive factors of success.

RESULTS:

We included 27 consecutive patients. The complete clinical and radiological response rates at M12 were 51.9% and 50%, respectively. The combined complete clinical-radiological response (deep remission) rate was 34.6%. No major adverse effects or changes in anal continence were reported. The perianal disease activity index decreased from 6.4 to 1.6 (p < 0.001) for all patients. The CAF-QoL score also decreased from 54.0 to 25.5 (p < 0.001). At the end of the study, M12, the CAF-QoL score was significantly lower only in patients with a complete combined clinical-radiological response relative to those without a complete clinical-radiological response (15.0 versus 32.8, p = 0.01). Having a multibranching fistula and infliximab treatment were associated with a combined complete clinical-radiological response.

CONCLUSIONS:

This study confirms reported efficacy data for the injection of MSC for complex anal fistulas in Crohn's disease. It also shows a positive impact on the quality of life of patients, particularly those for whom a combined clinical-radiological response was achieved.

2023-11-01·Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland

Allogenic stem cells for Crohn's anal fistulas: Treating early improves the deep remission rate

Article

作者: de Parades, Vincent ; Pommaret, Elise ; Akaffou, Mélissa ; Landemaine, Amandine ; Siproudhis, Laurent ; Fathallah, Nadia ; Bouguen, Guillaume ; Brochard, Charlène ; Haouari, Mohamed Amine ; Spindler, Lucas

Abstract:

Aim:

The aim of this study was to evaluate the real‐life clinical and radiological efficacy of darvadstrocel injection into complex perianal fistulas in Crohn's disease. Secondary endpoints were to assess symptomatic efficacy, adverse effects and factors associated with complete combined clinical‐radiological response (deep remission).

Methods:

After marketing the product in France, all first patients treated consecutively were included. A complete clinical response was defined by a complete closure of all external openings with no discharge on pressure. A complete radiological response (MRI), evaluated at least after six months of follow‐up, was defined by a completely fibrotic sequela without abscess. A deep remission was defined as the association of a complete clinical response with a complete radiological response.

Results:

A total of 43 patients were included (M/F: 22/21, median age 37 [26–45] years). The fistulas were already drained with seton(s) and were on biologic treatment. After a median follow‐up of 383 (359–505) days, 28 (65%) patients showed a clinical response (22 complete and 6 partial) and 16 (37%) achieved a deep remission. The Perineal Disease Activity Index decreased significantly after treatment: 39 (91%) patients reported symptomatic improvement in terms of discharge, pain, and induration, and 28 (65%) no longer had any perineal symptoms. No severe adverse events were reported. A short history of Crohn's disease <3 years was significantly associated with deep remission (OD 4.5 [1.0–19.1], p = 0.04).

Conclusion:

Darvadstrocel injection resulted in a clinical response for two thirds of patients and deep remission for one third. A shorter duration of Crohn's disease was associated with deep remission.

项与 Darvadstrocel ( TiGenix) 相关的新闻（医药）

2024-05-10

·药事纵横

武田2023净利润下降55%，将进行9亿美元重组

声明：因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）;本文不构成任何投资建议。5月9日，武田制药公布了2023财报（2023年4月~2024年3月）：全年营收42638亿日元，同比增长5.9%；净利润为1441亿日元，同比下降54.6%。按地区收入来看，美国收入最多，达21957亿日元；其次是欧洲和加拿大，收入9668亿日元；第三是日本本土，收入4514亿日元，其他地区收入情况如下：按产品收入来看，武田收入主要来源5大板块：消化、罕见病、血液制品、神经科学和肿瘤。其中，消化领域产品收入是最主要来源，2023年收入12162亿日元，同比增长11%。其中Entyvio(维多珠单抗)是该管线的顶梁柱支柱产品，2023年销售8009亿日元，同比增长14%。但是，武田降压药“Azilva”2023年仅销售336亿日元，同比大降54%。Azilva于2012年1月在日本上市，2021年销售额达到763亿日元。2021年6月，恒瑞医药的阿齐沙坦片获批，拿下国内首仿。而武田明星产品“Vyvanse”2023年销售4232亿日元，同比下降8%。Vyvanse于2003年首次被批准用于注意力缺陷/多动障碍。其成人适应症专利已于2023年 2 月 24 日到期，儿科适应症也于2023年 8 月 24 日到期。Sandoz、Teva 和 Mylan 等公司至少有 12 款 Vyvanse 仿制药即将推出。2023年由于武田失去了Azilva 和Vyvanse 的独家经营权，导致年利润下降超50%。再加上克罗恩病干细胞疗法 Alofisel和肺癌酪氨酸激酶抑制剂 Exkivity的研究失败，于是，武田决定对公司进行重组，提高未来几年的利润率。预计2024年将产生1400亿日元（约9亿美元）的一次性重组费用。武田表示，重组将包括优化员工、削减开支、砍管线。公司的目标是从2025开始，每年将核心利润率提高 1%~2.5%，最终达到 30%。武田研发管线财报中还提到，2023年武田共有18款药物从管线中剔除，包括：肺癌产品Exkivity、阿尔茨海默氏症药物DNL-919（ATV：TREM2）、异染性脑白质营养不良酶替代疗法TAK-611、治疗恶心和呕吐的候选药物 TAK-105、治疗伴有复杂肛瘘的克罗恩病的Cx601、针对帕金森病的TAK-071、癌症疗法TAK-981、细胞疗法 TAK-007、多发性骨髓瘤和实体瘤的TAK-573、实体瘤的TAK-102/TAK-103、多发性骨髓瘤的TAK-940以及预防寨卡病毒感染的TAK-426等。与此同时，有报道称：武田将关闭其圣地亚哥研究中心（拥有340名员工），将更多资源集中在有前途的后期研发管线上。武田首席执行官 Christophe Weber表示：“展望 2024 年，预计将有多达6个项目处于III 期开发中，通过开发将推进这些有前景的疗法，同时适度增加研发投资。”虽然 Vyvanse 等药物独家经营权的丧失对武田营收造成了影响，但该公司预计，至少在 2030 年之前，该公司面临的此类风险将有限。因此，预计2025年起能够恢复收入和利润增长。参考资料：https://www.takeda.com/newsroom/newsreleases/2024/takeda-announces-fy23-full-year-results-and-fy2024-outlook-pdf/活动推荐点击图片查看详细信息

财报临床3期专利到期

2024-05-09

·BioSpace

Takeda Lowers Profit Outlook Amid Vyvanse Loss of Exclusivity, Eyes $900M Restructuring in 2024

Pictured: Takeda's office in Cambridge, Massachusetts/iStock, hapabapa Takeda on Thursday released the business report for its 2023 fiscal year, touting a modest increase in annual revenue while forecasting a profit hit for the coming year tied to the continued sales erosion of its ADHD therapy Vyvanse (lisdexamfetamine dimesylate). For the fiscal year that ended March 31, 2024, Takeda booked more than $27 billion in revenue. This figure represents a 1.5% increase at constant exchange rates from its fiscal year 2023 revenue of $25.8 billion. Despite the revenue bump, Takeda’s net profit for the year dropped 57% to $925 million, from approximately $2 billion during the previous fiscal year. Takeda’s reported operating profit likewise took a 50.3% hit, dropping from $3.15 billion to $1.37 billion in the fiscal year 2023. According to the pharma’s investor presentation, the drop in reported operating profit could be attributed to higher operating expenditure as well as “impairments” with its Crohn’s disease stem cell therapy Alofisel (darvadstrocel) and lung cancer tyrosine kinase inhibitor Exkivity (mobocertinib). In October 2023, Alofisel failed its Phase III ADMIRE-CD II study, unable to significantly improve 24-week combined remission in patients with complex Crohn’s perianal fistulas. The company subsequently decided not to regulatory approval in the U.S., according to its presentation on Thursday. The same month, Takeda withdrew Exkivitiy globally after it failed the confirmatory Phase III EXCLAIM-2 study. Looking ahead to the rest of the current fiscal year, Takeda tempered investor expectations and lowered its core operating profit guidance by approximately 10%. The Japanese multinational now anticipates booking around $6.4 million (or ¥1 billion) in the coming year. Takeda’s forecast also includes a “flat to slightly declining” annual revenue. This annual guidance reflects the continued sales erosion that Takeda is expecting to weather as generic versions of its ADHD medicine Vyvanse hit the market. First approved in 2003, Vyvanse lost several crucial patent protections in 2023, including those that covered adult indications in February, and those for pediatric use in August. There are at least 12 impending generic version of Vyvanse from companies such as Sandoz, Teva and Mylan. Takeda has lined up several upcoming pipeline milestones to make up for Vyvanse’s loss of exclusivity. In the coming fiscal year, for instance, it is planning to launch a Phase III study of its tyrosine kinase 2 inhibitor zasocitinib in psoriatic arthritis, as well as a head-to-head study versus BMS’s Sotyktu (deucravacitinib) in psoriasis. The pharma is also awaiting a Phase III readout for its cholesterol 24-hydroxylase inhibitor soticlestat in the first half of the fiscal year. The drug candidate is being studied for Dravet syndrome or Lennox-Gastaut syndrome, two rare epileptic conditions. Aside from its promising pipeline, Takeda will also implement an “enterprise-wide efficiency program,” which will start in fiscal year 2024, according to its business report. The pharma expects this strategic initiative to cost nearly $900 million. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

临床3期上市批准财报细胞疗法

2024-02-12

·药事纵横

武田再砍6条管线

声明：因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）;本文不构成任何投资建议。武士刀起，管线落！在研发的道路上，杀伐决断，勇于放弃也是一种积极的策略。继去年半年报武田宣布砍掉4条管线后，近日又披露停止了6个管线项目。近期，多家全球知名药企纷纷揭晓了最新财报，除了各项财务数据备受瞩目外，其研发管线的战略调整同样引起了业界的广泛关注。尤其被终止的研发项目，它们背后的故事与经验教训对于整个行业而言都极具借鉴意义，有助于其他企业在研发道路上规避风险，少走弯路，减少不必要的探索。例如罗氏将从其研发管线中剔除5款神经学领域资产和3款肿瘤资产（包括2款死磕十多年的AD药物），旨在平衡整体投资组合价值并加速开发更有价值资产。辉瑞也砍掉3条管线，涉及到广谱抗真菌类，抗肿瘤药和1款B7H4/CD3双抗。除了罗氏、辉瑞等药企，武田制药在最新披露信息中显示，净利下降和管理层变动，也终止了6个研发项目。2023财年前三季度，武田全球总收入为3.21万亿日元（约合220亿美元），同比增长4.6%。净利润为1471亿日元，同比下降49%。该公司预计其2023财年营收将达到3.9万亿日元（合266亿美元）。武田公司表示，其利润的变化反映了仿制药的竞争、新冠肺炎疫苗收入的减少以及研发、数据和技术方面投资的增加。近期，武田在人事变动和对外合作方面也动作频频。CFO辞职，肿瘤学部门换帅首席财务官Costa Saroukos将于4月1日辞职，以便更接近他在澳大利亚的家人。他在这份工作上工作了六年，并帮助完成了制药史上最大的交易之一——2019 年以 620 亿美元收购夏尔。Takeda CEO Christophe Weber评价称其在此交易中发挥了重要作用。此外，武田还宣布前CRISPR Therapeutics公司首席医学官PK Morrow于1月29日接替ChrisArendt担任肿瘤学部门负责人。Christophe Weber, Takeda CEO在对外合作方面，今年2月初武田花费3亿美元购买Protagonist的PhIII罕见病药物。去年12月JCR Pharmaceuticals宣布武田决定停止与JCR合作，开发使用腺相关病毒（AAV）结合JCR J-Brain Cargo技术的基因疗法。近日有媒体报道，武田制药终止了六条研发管线。这些项目包括治疗伴有复杂肛瘘的克罗恩病的Cx601、针对帕金森病的TAK-071、多发性骨髓瘤和实体瘤的TAK-573、实体瘤的TAK-102/TAK-103、多发性骨髓瘤的TAK-940以及预防寨卡病毒感染的TAK-426。这些决策主要基于临床试验结果未达到预期、战略调整以及对市场需求和流行病学的评估。武田制药表示，这些举措是为了最大化公司价值和资源利用效率。具体项目和原因如下：研发总裁Andy Plump在更新研发管线时提到，武田在细胞治疗方面将聚焦通用型细胞治疗的研发，削减了其他处于I期临床试验阶段的3项CAR-T细胞治疗项目，分别为TAK-102、TAK-103和TAK-940。TAK-102和TAK-103针对实体肿瘤开发，而TAK-940则是为CD19针对多发性骨髓瘤。此外武田在本周四宣布，将于2024财年上半年在全球范围内启动其正在研究中的口服ORX2激动剂TAK-861在1型嗜睡症的全球三期临床试验，并放弃在2型嗜睡症中开发该候选药物的计划。在对112名NT1患者进行的具有主要和关键次要终点的P2b研究中取得积极结果后，武田开发了几种食欲素受体激动剂，并有望扩大特许经营权的规模。参考资料：https://assets-dam.takeda.com/image/upload/v1706756054/Global/Investor/Financial-Results/FY2023/Q3/q3_fy2023_press_release.pdf

财报基因疗法疫苗并购高管变更

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

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研发状态

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10 条最早获批的记录,

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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

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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	日本	Takeda Pharmaceutical Co., Ltd.	2019-03-06
克罗恩病	临床3期	美国	Tigenix SAU	2017-09-15
克罗恩病	临床3期	比利时	Tigenix SAU	2017-09-15
克罗恩病	临床3期	加拿大	Tigenix SAU	2017-09-15
克罗恩病	临床3期	捷克	Tigenix SAU	2017-09-15
克罗恩病	临床3期	丹麦	Tigenix SAU	2017-09-15
克罗恩病	临床3期	法国	Tigenix SAU	2017-09-15
克罗恩病	临床3期	德国	Tigenix SAU	2017-09-15
克罗恩病	临床3期	匈牙利	Tigenix SAU	2017-09-15
克罗恩病	临床3期	以色列	Tigenix SAU	2017-09-15

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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


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	顧艱齋夢衊積遞獵選築(鹽蓋鬱蓋觸網顧顧廠簾) = did not meet its primary endpoint of combined remission at 24 weeks, based on topline data 鑰醖顧窪範繭獵憲壓廠 (餘廠鹹壓窪繭築蓋糧艱 ) 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	遞膚糧窪窪願鏇願繭淵(淵鏇膚鹽範鏇鬱選築鑰) = 鹹觸網蓋遞餘鬱構夢鏇衊壓廠淵積積鏇願鑰艱 (壓窪鹽顧觸積壓鏇製鑰, 38.5 ~ 79.6) 更多	积极	2022-09-23
NCT03706456 (CTgov)	临床3期	克罗恩病 \| 克罗恩病引起的肛周瘘	22	Darvadstrocel	糧築衊廠壓築鹽夢淵鬱(繭齋夢衊壓窪鹽齋積醖) = 壓衊廠獵願糧艱積夢廠網獵淵壓鬱壓選鑰築窪 (製範獵顧廠齋範範繭構, 膚製鏇窪遞觸簾衊廠網 ~ 鑰艱蓋鑰襯齋簾鏇艱鏇) 更多	-	2021-10-07
NCT01541579 (Pubmed \| Lancet) 人工标引	临床3期	克罗恩病 \| 肛瘘	212	Cx601	構願艱顧醖鬱襯糧蓋構(觸構範齋鹽鏇衊淵艱遞) = 廠齋廠鏇鏇艱築顧衊獵窪築鏇簾鹽糧窪壓窪淵 (夢窪鬱構鏇繭鏇選衊夢 ) 更多	积极	2016-09-24
				Placebo	構願艱顧醖鬱襯糧蓋構(觸構範齋鹽鏇衊淵艱遞) = 壓構憲醖壓簾鏇製繭願窪築鏇簾鹽糧窪壓窪淵 (夢窪鬱構鏇繭鏇選衊夢 ) 更多