ASPIRO: A Phase 1/2/3, Randomized, Open-Label, Ascending-Dose, Delayed-Treatment Concurrent Control Clinical Study to Evaluate the Safety and Efficacy of AT132, an AAV8-Delivered Gene Therapy in X-Linked Myotubular Myopathy (XLMTM) Patients

X-linked myotubular myopathy (XLMTM) is a rare and serious condition present at birth where the muscles do not work properly. There are currently no therapies for this serious condition.
The protein myotubularin is needed for muscle development and movement. A gene called MTM1 tells the body to make myotubularin. XLMTM is caused by changes, or mutations, in the MTM1 gene. Changes in the MTM1 gene causes low levels of myotubularin to be made, so the muscles do not work properly. XLMTM may also affect the liver, and in some cases, this can be dangerous and threaten the patient´s life.
Gene therapy is a way of getting a healthy copy of a gene into the body. This allows the body's cells to make a normal protein that may reduce disease symptoms. AT132 is a gene therapy that gets a healthy MTM1 gene into the body to help improve muscle development and function in young children with the disease. AT132 does not treat liver disease, and because of the way the treatment works, it may make liver problems worse.
AT132 was the gene therapy treatment given to children who participated in this study and is not available to the public. In this study, AT132 was given to children for the first time. Due to the occurrence of severe complications and fatalities associated with administration of AT132, the study has been stopped and no further participants will be enrolled.
The main aim of the study is to check how long young children need machines to support breathing (ventilation support) after AT132.
Due to the occurrence of severe complications and fatalities associated with administration of AT132, the study has been stopped and no further participants will be enrolled. This study included children with XLMTM under 5 years old who had breathing problems caused by XLMTM. They couldn't take part if they were born prematurely, recently had surgery, had liver disease or other condition or disease the study doctor thought was medically important. The study did enroll participants with medically significant liver disease.
This is an open-label study. This means that young children and their caregivers, and clinic staff know that young children received AT132. This study was designed with 2 parts and is now in a long-term follow-up phase to collect information on the safety and improvements in muscle function in the children who received AT132.
In Part 1, small groups of young children were given different doses of AT132, with one group receiving a lower dose and one group receiving a higher dose of AT132. The purpose of giving the two doses was to determine which dose was best for treating the muscle disease. After receiving AT132, a medical panel of experts reviewed each child for safety and for how their muscles responded. AT132 did not demonstrate appropriate safety at either dose. Administration of AT132 was stopped. Children who received AT132 are being monitored for 10 years for safety and to understand how their muscles function over time.

开始日期2017-08-02

申办/合作机构

Astellas Gene Therapies, Inc.

100 项与 Resamirigene bilparvovec(Astellas) 相关的临床结果

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100 项与 Resamirigene bilparvovec(Astellas) 相关的转化医学

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100 项与 Resamirigene bilparvovec(Astellas) 相关的专利（医药）

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项与 Resamirigene bilparvovec(Astellas) 相关的文献（医药）

2024-09-16·RESPIRATORY RESEARCH

An algorithm for discontinuing mechanical ventilation in boys with x-linked myotubular myopathy after positive response to gene therapy: the ASPIRO experience.

Article

作者: Smith, Barbara K ; Prasad, Suyash ; Graham, Robert J ; Lilien, Charlotte ; Sawnani, Hemant ; Edel, Lisa ; MacBean, Victoria ; Perez, Geovanny F ; Demirel, Nadir ; Rafferty, Gerrard F ; Schön, Carola ; Rico, Salvador ; Amin, Reshma ; Syed, Faiza ; Sarazen, Micaela

X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital myopathy. Most (80%) children with XLMTM have profound muscle weakness and hypotonia at birth resulting in severe respiratory insufficiency, the inability to sit up, stand or walk, and early mortality. At birth, 85-90% of children with XLMTM require mechanical ventilation, with more than half requiring invasive ventilator support. Historically, ventilator-dependent children with neuromuscular-derived respiratory failure of this degree and nature, static or progressive, are not expected to achieve complete independence from mechanical ventilator support. In the ASPIRO clinical trial (NCT03199469), participants receiving a single intravenous dose of an investigational gene therapy (resamirigene bilparvovec) started showing significant improvements in daily hours of ventilation support compared with controls by 24 weeks post-dosing, and 16 of 24 dosed participants achieved ventilator independence between 14 and 97 weeks after dosing. At the time, there was no precedent or published guidance for weaning chronically ventilated children with congenital neuromuscular diseases off mechanical ventilation. When the first ASPIRO participants started showing dramatically improved respiratory function, the investigators initiated efforts to safely wean them off ventilator support, in parallel with primary protocol respiratory outcome measures. A group of experts in respiratory care and physiology and management of children with XLMTM developed an algorithm to safely wean children in the ASPIRO trial off mechanical ventilation as their respiratory muscle strength increased. The algorithm developed for this trial provides recommendations for assessing weaning readiness, a stepwise approach to weaning, and monitoring of children during and after the weaning process.

2024-01-01·EBioMedicine

Effects of gene replacement therapy with resamirigene bilparvovec (AT132) on skeletal muscle pathology in X-linked myotubular myopathy: results from a substudy of the ASPIRO open-label clinical trial

Article

作者: Meng, Hui ; Sepulveda, Bryan ; Smith, Barbara K ; Conner, Edward ; Prom, Mariah J ; Dowling, James J ; Kuntz, Nancy L ; Lawlor, Michael W ; Schoser, Benedikt ; Neuhaus, Sarah ; Blaschek, Astrid ; Seferian, Andreea M ; Margeta, Marta ; Sewry, Caroline A ; Vanden Avond, Mark ; Kumar, Suresh N ; James, Emma S ; Rico, Salvador ; Shieh, Perry B ; Danielson, Susan ; Tsuchiya, Etsuko ; Müller-Felber, Wolfgang ; Sadhu, Chanchal ; Ott, Emily ; Saade, Dimah N ; Krakau, Paul ; Beatka, Margaret ; Jones, Karra A ; Bönnemann, Carsten G ; Varfaj, Fatbardha ; Christensen, Sarah ; Prasad, Suyash ; Wells, Clive ; Foley, A Reghan ; Qasim, Ummulwara R ; Miller, Weston ; Gordish-Dressman, Heather ; Beggs, Alan H ; Lee, Jun

BACKGROUND:

X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital muscle disease caused by mutations in the MTM1 gene that result in profound muscle weakness, significant respiratory insufficiency, and high infant mortality. There is no approved disease-modifying therapy for XLMTM. Resamirigene bilparvovec (AT132; rAAV8-Des-hMTM1) is an investigational adeno-associated virus (AAV8)-mediated gene replacement therapy designed to deliver MTM1 to skeletal muscle cells and achieve long-term correction of XLMTM-related muscle pathology. The clinical trial ASPIRO (NCT03199469) investigating resamirigene bilparvovec in XLMTM is currently paused while the risk:benefit balance associated with this gene therapy is further investigated.

METHODS:

Muscle biopsies were taken before treatment and 24 and 48 weeks after treatment from ten boys with XLMTM in a clinical trial of resamirigene bilparvovec (ASPIRO; NCT03199469). Comprehensive histopathological analysis was performed.

FINDINGS:

Baseline biopsies uniformly showed findings characteristic of XLMTM, including small myofibres, increased internal or central nucleation, and central aggregates of organelles. Biopsies taken at 24 weeks post-treatment showed marked improvement of organelle localisation, without apparent increases in myofibre size in most participants. Biopsies taken at 48 weeks, however, did show statistically significant increases in myofibre size in all nine biopsies evaluated at this timepoint. Histopathological endpoints that did not demonstrate statistically significant changes with treatment included the degree of internal/central nucleation, numbers of triad structures, fibre type distributions, and numbers of satellite cells. Limited (predominantly mild) treatment-associated inflammatory changes were seen in biopsy specimens from five participants.

INTERPRETATION:

Muscle biopsies from individuals with XLMTM treated with resamirigene bilparvovec display statistically significant improvement in organelle localisation and myofibre size during a period of substantial improvements in muscle strength and respiratory function. This study identifies valuable histological endpoints for tracking treatment-related gains with resamirigene bilparvovec, as well as endpoints that did not show strong correlation with clinical improvement in this human study.

FUNDING:

Astellas Gene Therapies (formerly Audentes Therapeutics, Inc.).

2023-12-01·The Lancet. Neurology

Safety and efficacy of gene replacement therapy for X-linked myotubular myopathy (ASPIRO): a multinational, open-label, dose-escalation trial

Article

作者: Kuntz, Nancy L ; Müller-Felber, Wolfgang ; Smith, Barbara K ; Bönnemann, Carsten G ; Servais, Laurent ; Varfaj, Fatbardha ; Childers, Martin K ; Miller, Weston ; Neuhaus, Sarah ; Alfano, Lindsay N ; Muntoni, Francesco ; Beggs, Alan H ; Lawlor, Michael W ; Buj-Bello, Ana ; Shieh, Perry B ; Rico, Salvador ; Han, Cong ; Mavilio, Fulvio ; Blaschek, Astrid ; Lee, Jun ; MacBean, Vicky ; Murtagh, Michael ; Foley, A Reghan ; Graham, Robert J ; Prasad, Suyash ; Noursalehi, Mojtaba ; Saade, Dimah N ; Seferian, Andreea M ; Dowling, James J ; Duong, Tina ; James, Emma S ; Jain, Minal ; Coats, Julie

BACKGROUND:

X-linked myotubular myopathy is a rare, life-threatening, congenital muscle disease observed mostly in males, which is caused by mutations in MTM1. No therapies are approved for this disease. We aimed to assess the safety and efficacy of resamirigene bilparvovec, which is an adeno-associated viral vector serotype 8 delivering human MTM1.

METHODS:

ASPIRO is an open-label, dose-escalation trial at seven academic medical centres in Canada, France, Germany, and the USA. We included boys younger than 5 years with X-linked myotubular myopathy who required mechanical ventilator support. The trial was initially in two parts. Part 1 was planned as a safety and dose-escalation phase in which participants were randomly allocated (2:1) to either the first dose level (1·3 × 10¹⁴ vector genomes [vg]/kg bodyweight) of resamirigene bilparvovec or delayed treatment, then, for later participants, to either a higher dose (3·5 × 10¹⁴ vg/kg bodyweight) of resamirigene bilparvovec or delayed treatment. Part 2 was intended to confirm the dose selected in part 1. Resamirigene bilparvovec was administered as a single intravenous infusion. An untreated control group comprised boys who participated in a run-in study (INCEPTUS; NCT02704273) or those in the delayed treatment cohort who did not receive any dose. The primary efficacy outcome was the change from baseline to week 24 in hours of daily ventilator support. After three unexpected deaths, dosing at the higher dose was stopped and the two-part feature of the study design was eliminated. Because of changes to the study design during its implementation, analyses were done on an as-treated basis and are deemed exploratory. All treated and control participants were included in the safety analysis. The trial is registered with ClinicalTrials.gov, NCT03199469. Outcomes are reported as of Feb 28, 2022. ASPIRO is currently paused while deaths in dosed participants are investigated.

FINDINGS:

Between Aug 3, 2017 and June 1, 2021, 30 participants were screened for eligibility, of whom 26 were enrolled; six were allocated to the lower dose, 13 to the higher dose, and seven to delayed treatment. Of the seven children whose treatment was delayed, four later received the higher dose (n=17 total in the higher dose cohort), one received the lower dose (n=7 total in the lower dose cohort), and two received no dose and joined the control group (n=14 total, including 12 children from INCEPTUS). Median age at dosing or enrolment was 12·1 months (IQR 10·0-30·9; range 9·5-49·7) in the lower dose cohort, 31·1 months (16·0-64·7; 6·8-72·7) in the higher dose cohort, and 18·7 months (10·1-31·5; 5·9-39·3) in the control cohort. Median follow-up was 46·1 months (IQR 41·0-49·5; range 2·1-54·7) for lower dose participants, 27·6 months (24·6-29·1; 3·4-41·0) for higher dose participants, and 28·3 months (9·7-46·9; 5·7-32·7) for control participants. At week 24, lower dose participants had an estimated 77·7 percentage point (95% CI 40·22 to 115·24) greater reduction in least squares mean hours per day of ventilator support from baseline versus controls (p=0·0002), and higher dose participants had a 22·8 percentage point (6·15 to 39·37) greater reduction from baseline versus controls (p=0·0077). One participant in the lower dose cohort and three in the higher dose cohort died; at the time of death, all children had cholestatic liver failure following gene therapy (immediate causes of death were sepsis; hepatopathy, severe immune dysfunction, and pseudomonal sepsis; gastrointestinal haemorrhage; and septic shock). Three individuals in the control group died (haemorrhage presumed related to hepatic peliosis; aspiration pneumonia; and cardiopulmonary failure).

INTERPRETATION:

Most children with X-linked myotubular myopathy who received MTM1 gene replacement therapy had important improvements in ventilator dependence and motor function, with more than half of dosed participants achieving ventilator independence and some attaining the ability to walk independently. Investigations into the risk for underlying hepatobiliary disease in X-linked myotubular myopathy, and the need for monitoring of liver function before gene replacement therapy, are ongoing.

FUNDING:

Astellas Gene Therapies.

项与 Resamirigene bilparvovec(Astellas) 相关的新闻（医药）

2024-10-15

·同写意

基因疗法第一网红，翻盘越来越难了

本届大会以“共建创新生态共赢产业未来”为主题，聚焦生物医药出海与国际化创新、创新药投融资、医疗器械等产业发展风向标，打造“高端化、国际化、专业化、立体化”的年度盛会。提到基因疗法，蓝鸟生物是绕不开的一个存在。 1992年，两位麻省理工学院的研究人员创立了蓝鸟生物的前身Genetix Pharmaceuticals。经过近20年的坚持，蓝鸟生物在基因疗法的努力方显成效。 2010年，《nature》发布了一项临床试验结果，在蓝鸟生物Lentiglobin基因疗法的临床试验中，一位患有重型β地中海贫血的患者成功摆脱输血治疗。要知道，此前对于地中海贫血患者只有终身输血这一治疗方案，而蓝鸟生物则为地中海贫血患者带来新的希望。蓝鸟生物也由此一战成名，获得了众多投资人的青睐。2013年6月，蓝鸟生物登陆纳斯达克。此后，蓝鸟生物一路向上，不仅收获了众多荣誉，2017年被评为全球最聪明的50家公司之一，2018年被评为最有可能被收购的十大并购标的之一；公司股价更是水涨船高，2018年时市值最高曾逼近300亿美金。然而，命运总是充满波折与意想不到。2020年，蓝鸟生物首款基因疗法产品获批，这本该是其高光时刻的开始，没想到却成了其过山车式命运的最高点。自此之后，蓝鸟生物的一路向下，如今市值已不足1亿美金。更糟糕的是，当前公司负面不断，产品安全性问题争议持续，蓝鸟生物的处境变得越来越危险…… 1 7名患者患癌风波日前，发表在《新英格兰医学杂志》上的一项研究，让蓝鸟生物陷入了风波。该研究是针对基因疗法Skysona治疗脑肾上腺脑白质营养不良2-3期研究（ALD-102和 ALD-104）和一项正在进行的随访研究（LTF-304）数据。结果不容乐观：67名儿童患者中，7 名接受Skysona治疗的儿童患上了血癌。6例被诊断为骨髓增生异常综合征（MDS），在Skysona治疗后 14 至 92 个月内出现；另一名患者在57个月时被诊断出患有急性髓性白血病（AML）。目前，6 例MDS患者接受了干细胞移植治疗，1 例患者因移植物抗宿主病而死亡。AML患者仍然活着，并且对移植表现出良好的反应。导致7名儿童患癌的根源，是Skysona。 Skysona作为一种基因疗法，通过将ABCD1基因的功能性拷贝递送到患者的造血干细胞中来发挥作用，从而促进能够表达功能性ALDP蛋白的成熟单核细胞的产生。但其存在风险，Skysona疗法中的慢病毒载体整合到原癌基因中，会诱发血液瘤。Skysona的标签上带有血液系统恶性肿瘤的黑框警告，包括MDS等“危及生命的病例”。而上述7 名接受Skysona 治疗的儿童患上了血癌，大致原因也是如此。据研究人员称，新出现的血癌与与癌症相关基因中的克隆向量插入有关，同时也与某些感兴趣位点的体细胞突变累积有关，包括KRAS、WT1和CDKN2A基因中的突变。虽然患癌风波将会如何影响蓝鸟还不得而知，但这无疑再次为我们敲响了安全性警钟。 2 安全、安全、安全安全问题一直是悬在基因疗法之上的达摩克里斯之剑。 1999年，一名18岁少年在接受腺病毒基因疗法后发生严重免疫反应死亡，这是第一例因基因疗法而死亡的患者。这一事件，也使得FDA收紧了对于基因疗法的临床审批，基因疗法因此沉寂了十余年之久。直到2017年12月，美国首个基因疗法获批上市，由Spark Therapeutics开发的Luxturna基因疗法，用于治疗眼科疾病。基因疗法得以再度活跃。不过，安全问题并未随着基因疗法获批上市而消失。相反，安全问题如同一颗定时炸弹，仍然威胁着基因疗法的发展。 2021年2月，蓝鸟基因疗法bb1111对镰状细胞贫血患者的1/2期临床试验中，产生了两个疑似血液肿瘤病例，一位受试者被诊断为急性髓性白血病，另一名患者发生了骨髓增生异常综合征。因为可能存在的致癌风险，FDA叫停了蓝鸟生物bb1111的临床试验。与此同时，已经在欧洲获批上市的Zynteglo，因为与其使用了相同的慢病毒粒载体，存在潜在的安全问题，也被蓝鸟生物暂停销售。经过5个月的评判，最终证明治疗收益大于风险，Zynteglo得以重新开始销售，而bb1111临床试验也得以重启。但就在半年后，bb1111的临床试验再次遇到问题。 2021年，一名青少年患者在接受bb1111 治疗后出现了持续性非输血依赖性贫血，18岁以下镰状细胞病患者的临床研究进被部分搁置。虽然相比30年前，基因疗法的安全性有了很大的提升，但目前基因疗法仍然难言彻底安全，而这也绝非蓝鸟生物一家之忧。 2020年8月，被安斯泰来30亿美元收购的基因疗法公司Audentes，其核心产品AT132在临床试验中出现了三位患者死亡。 2020年10月，一名患者在接受Lysogene AAV基因治疗后去世。如今，Skysona的致癌风波再次发酵，告诉我们基因疗法的发展仍然如履薄冰，一不小心就会因为安全问题再次坠入深渊。 3 当然，尽管蓝鸟生物这一基因疗法的先驱坠落，但这并不会影响基因疗法仍将持续向上的事实。仅放眼国内市场，随着资金的涌入，也已经出现了一批基因疗法的新兴玩家，如博雅辑因、合生基因、纽福斯、中因科技等。其中，纽福斯的AAV基因治疗药物NR082和中因科技的基因治疗药物ZVS101e，都获得了FDA的孤儿药认证。不过，对于国内玩家来说，蓝鸟生物的经历在前，安全问题同样也是部分国内玩家，需要面临的挑战。蓝鸟生物从风光无限到无奈坠落，也不过三年多的光景。这背后，也映射了市场对于基因疗法的态度变化，从未知的担心，再到充满期待的追捧，再到如今归于平静。不少人已经意识到，虽然长远来看，基因疗法仍然具有无限的潜力、广阔的发展空间，但是短期来看，基因疗法针对适应症多为罕见病，仍属于一个小众治疗手段。基因疗法中像Zolgensma一样的只是少数，大多数都如同蓝鸟生物一样，深陷亏损的泥潭之中。从全球视角来看，基因疗法的安全性和商业化问题仍然还未完全找到答案。而在这之前，基因疗法仍是一个充满无限可能但又危险重重的地方。同写意媒体矩阵，欢迎关注↓↓↓

基因疗法并购临床结果

2024-10-08

·EndPoints

Astellas places new bet on gene therapy in $50M upfront deal with UK startup

As it works to rebuild from an earlier gene therapy setback, Astellas is doubling down on the one-and-done modality in a new deal with a London-based startup already in the clinic. Astellas said Tuesday it will pay $30 million upfront and invest $20 million in AviadoBio in exchange for the chance to exclusively develop and commercialize the startup’s AAV-based gene therapy for people with frontotemporal dementia with progranulin mutations, or FTD-GRN. Investigators dosed the first patient with the experimental medicine, codenamed AVB-101, in April. The Phase 1/2 also opened in the US in July. Astellas could deliver up to $2.18 billion in license fees and milestone payments, the companies said. Astellas could develop AVB-101 for FTD-GRN and potentially other indications, the duo added. AviadoBio mentions ALS as another focus area for the startup, according to its website. Patients with FTD, an early form of dementia, can die within three to 13 years after diagnosis, the companies said. Attention, memory, mobility, problem solving and other functions deteriorate in adults with the neurodegenerative disease. AviadoBio’s gene therapy delivers a working copy of the GRN gene into the brain with the goal of halting the disease’s progress. The Astellas investment provides a boost to AviadoBio, which does not appear to have raised another financing round since unveiling an $80 million Series A in December 2021. Leading the upstart is former Novartis Gene Therapies chief business officer Lisa Deschamps. “Together, we can further accelerate delivering this investigational medicine to families around the world who so desperately need treatment options for FTD-GRN and other neurological diseases,” Deschamps said in a press release, noting the company is completing dosing in the first cohort of the ASPIRE-FTD study. The AviadoBio tie-up marks a further bet on gene therapy for Astellas, which ran into a major setback in 2020 and 2021, when four boys died after receiving the company’s gene therapy for a rare neuromuscular disease known as X-linked myotubular myopathy. “People tend to look at the four boys’ deaths. And that’s a very unfortunate and tragic situation,” Astellas CEO Naoki Okamura told Endpoints last month . “On the other hand, there are healthier boys who received [the therapy] and survived for three to five years already. So we believe in the power of gene therapy to really make the difference.” Astellas is working with Kate Therapeutics to improve the safety of the Audentes gene therapy, which is known as resamirigene bilparvovec, or AT132. The drugmaker also has Phase 1-stage gene therapies for Pompe disease (zocaglusagene nuzaparvovec, or AT845) and ASP2016 for cardiomyopathy associated with Friedreich’s ataxia. It also took a write-down in April on a preclinical Friedreich’s ataxia gene therapy known as AT808 from the Audentes buyout. Meanwhile, multiple drugmakers are pulling back from gene therapy R&D, including Pfizer, while a small number of startups have been able to reel in large financing rounds to carry forward their work in the field. The Japanese pharmaceutical company has a gene therapy R&D and manufacturing footprint in the Bay Area; Sanford, NC; and Tsukuba, Japan.

基因疗法并购临床1期

2024-09-04

·佰傲谷BioValley

安斯泰来关闭一家基因治疗工厂

近日，根据Biospace报道，Astellas（安斯泰来）公司旗下的Astellas Gene Therapies将关闭其位于旧金山的一家基因治疗工厂，并将基因治疗生产转移至北卡罗来州的另一家工厂。受此影响，将裁员至少17人，影响数十人。根据安斯泰来发言人在一封邮件中所诉，该举动将会影响100名员工。工厂关闭原因 Astellas Gene Therapies的发言人表示，该工厂正在关闭中，预计将于2025年3月完成。在一份声明中写道，安斯泰来一直在优先考虑资源，并做出简化运营。在评估了其腺病毒的需求后，该公司决定关闭该设施，并将所有计划和项目转移至Astellas Gene Therapies位于北卡罗来州的另一家工厂。尽管位于旧金山的工厂关闭、计划转移，但是Astellas Gene Therapies在加利福尼亚州的业务仍然存在。今年5月，安斯泰来宣布在旧金山开设西海岸创新中心，占地约15万平方英尺，是安斯泰来基因治疗研究和开发业务的中心，包括Astellas Gene Therapies。为何腺病毒需求下降？在评估了其腺病毒的需求后，安斯泰来决定关闭一家大型生物制造工厂，说明安斯泰来对于腺病毒的需求下降。在了解了安斯泰来在AAV基因治疗的失败史后，就明白安斯泰来确实是对腺病毒的需求不高了。安斯泰来开始探足基因治疗可以追溯到2014年与哈佛大学的合作，到正式重点部署AAV基因治疗，是在2019年以30亿美元收购了Audentes公司。然后，安斯泰来的噩梦就来了。先是X-连锁肌小管性肌病（XLMTM）AAV基因疗法AT132，由于接连的临床死亡事件（在2020年5月、2020年6月、2020年8月、2021年9月累计报告了四例患者死亡严重不良事件），期间遭到FDA两度喊停。目前，小编还未查到AT132解除临床搁置的消息。 2022年4月，安斯泰来终止了来自Audentes的3条杜氏肌营养不良症（DMD）AAV临床前管线，AT702、AT751和AT753。 2022年6月，安斯泰来又一款AAV基因疗法AT845临床试验被FDA叫停，原因是一名接受AT845治疗的晚发型庞贝病患者报告了周围感觉神经病不良事件。该临床搁置于2023年1月解除。延伸阅读： 30亿美元收购逐渐归零，安斯泰来又一款基因疗法被喊停 30亿美元收购败笔，安斯泰来终止多项基因治疗产品开发，累计5.6亿美元损失记账 AAV基因治疗的连续失败，以及多款管线的删减，安斯泰来对30亿美元收购Audentes已经进行了资产减值评估。目前，在安斯泰来官网的管线图上，来自Audentes公司的AAV临床管线仅有3条，分别是妾身未明的AT132（临床2期）、身具前科的AT845（临床1/2期）、以及一款新提的弗里德赖希共济失调相关心肌疾病项目ASP2016（临床1期）。其它基因治疗项目还未推进临床。安斯泰来的基因治疗项目（图片来源：参考资料2）如果除去AT132，也就仅有两款AAV产品需要生产临床制剂，因为都处于早期临床，产量要求也不高，因此，对于腺病毒载体的需求就下降了。小结除了AAV基因治疗，细胞治疗也是安斯泰来看好的方向。为了加强自身在细胞治疗领域的地位，安斯泰来于2018年收购了Universal Cells，但是在2023年终止与Adaptimmune公司的合作中，似乎暴露出Universal Cells的干细胞技术平台可能存在问题。感觉安斯泰来在细胞治疗上，也岌岌可危...... 延伸阅读：终止TCR-T合作，安斯泰来艰难的CGT之旅（本文仅代表作者观点，不代表平台立场）参考资料： 1.https://www.biospace.com/job-trends/astellas-gene-therapies-to-close-biomanufacturing-facility-affecting-about-100-employees 2.https://www.astellas.com/en/innovation/pipeline 本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处 · · · · · · · ·

基因疗法并购

100 项与 Resamirigene bilparvovec(Astellas) 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15121

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
先天性肌病	临床2期	-	Astellas Gene Therapies, Inc.	-
类风湿关节炎	临床1期	中国	珠海市丽珠单抗生物技术有限公司	2014-07-08

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临床结果

适应症

分期

评价

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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


Aspiro (Biospace) 人工标引	N/A	先天性肌病	24	AT132 (high-dose)	積廠艱襯選願壓醖構範(淵膚壓鹹繭衊鏇淵醖膚) = 遞製醖積衊積衊糧構壓蓋憲餘廠鹽艱襯壓襯襯 (齋壓廠襯鑰鏇製襯構鹽 ) 更多	不佳	2023-11-16
				AT132 (lower dose)	積廠艱襯選願壓醖構範(淵膚壓鹹繭衊鏇淵醖膚) = 製夢憲襯憲糧憲廠蓋鏇蓋憲餘廠鹽艱襯壓襯襯 (齋壓廠襯鑰鏇製襯構鹽 ) 更多
NCT03199469 (ASPIRO, PRNewswire) 人工标引	临床2/3期	先天性肌病	24	AT132 1.3 x 1014 vg/kg	(鑰壓醖壓餘顧鑰餘繭築) = 鹹鹹憲製蓋製網廠衊餘鬱鬱醖製製鬱範簾鬱齋 (蓋壓鏇窪壓艱積蓋淵憲 ) 更多	积极	2023-11-15
				AT132 3.5 x 1014 vg/kg	(鑰壓醖壓餘顧鑰餘繭築) = 網糧淵構餘壓範願鹹製鬱鬱醖製製鬱範簾鬱齋 (蓋壓鏇窪壓艱積蓋淵憲 ) 更多
ADA2021	N/A	糖尿病心肌病	-	AT-001	鏇窪築範襯鑰網構網鹹(鏇範繭鏇衊鬱襯醖艱鏇) = 夢膚顧艱壓願網窪構鬱廠鑰繭衊廠遞鹹衊築願 (製窪鏇廠蓋蓋夢選廠蓋 ) 更多	-	2021-06-01
				Vehicle	鏇窪築範襯鑰網構網鹹(鏇範繭鏇衊鬱襯醖艱鏇) = 鑰衊願積蓋糧範襯遞選廠鑰繭衊廠遞鹹衊築願 (製窪鏇廠蓋蓋夢選廠蓋 ) 更多