新闻速递：Audentes公司罕见病基因治疗计划在第三位患者死亡后无限期推迟
ASPIRO临床试验第三例患者死亡事件发生后，美国Audentes Therapeutics公司宣布无限期推迟其寻求监管部门批准罕见病基因疗法的计划。
ASPIRO临床试验旨在评估针对X连锁肌管肌病（XLTM）患者的AT132基因疗法。XLTM是一种罕见的神经肌肉疾病，主要影响男性，导致肌肉无力，严重者可能呼吸困难，因呼吸衰竭而致命。这种遗传性疾病在10岁时的死亡率约为25%。AT132是一种以腺嘌呤相关病毒（AAV）为基础的基因疗法，旨在传递XLMTM中缺失的MTM1基因。
据Audentes说，初步调查结果显示，第三名患者的直接死因是胃肠道出血。死亡的三名患者都在初次给药后的3到4周内开始出现肝功能不全的症状。
Audentes去年被日本制药公司Astellas收购，在披露前两名患者死亡后，于6月被迫搁置了ASPIRO试验。Audentes与ASPIRO研究人员和独立数据监测委员会一起，继续密切监测所有参与研究的患者。Audentes正在调查这三名患者为什么会出现进展性肝功能不全。尽管这项研究目前仍在进行中，但Audentes坚持认为，没有其他参与试验的患者出现类似的肝功能不全。
原文：https://www.pmlive.com/pharma_news/audentes_rare_disease_gene_therapy_programme_indefinitely_delayed_after_third_patient_death_1347266#.X0RTjjlkfZ8.twitter?SQ_DESIGN_NAME=2&
Audentes’ rare disease gene therapy programme delayed after third patient deathThird patient death caused by gastrointestinal bleeding
Audentes Therapeutics has indefinitely delayed plans to seek regulatory approval for its rare disease gene therapy after the death of a third patient involved in a clinical trial of the drug.
This was the third death of a patient involved in the Audentes’ ASPIRO clinical trial, which is evaluating its AT132 gene therapy in patients with X-linked myotubular myopathy (XLTM), a rare neuromuscular disease.
XLTM mainly affects males and causes muscle weakness that ranges in severity from mild to life-threatening. In severe forms of the disease, the weakened muscle make breathing difficult and can lead to respiratory failure. The genetic disorder has a mortality rate of around 25% by the age of ten.
AT132 is an aden-associated virus (AAV) based gene therapy that is designed to deliver the MTM1 gene deficient in XLMTM. According to Audentes, preliminary findings show that the immediate cause of death of the third patient was gastrointestinal bleeding.
The patient ws one of three study participants who had received AT132 at a dose of 3x1014 vg/kg, the higher dose, who subsequently began to demonstrate signs of liver dysfunction within three to four weeks after initial dosing.
The three patients also demonstrated evidence of pre-existing hepatobiliary disease, although over half of the patients enrolled in the study also showed evidence of the same pre-existing conditions.
Audentes, which was bought by Japanese pharma company Astellas last year, was forced to put the ASPIRO trial on hold in June after disclosing the first two patient deaths.
“Audentes, together with the ASPIRO investigators and independent Data Monitoring Committee, continues to closely monitor all patients enrolled in the study. Additionally, Audentes’ investigation into why these three patients developed progressive liver dysfunction is ongoing,” the company said in a statement.
Although the study is currently on hold, Audentes maintained that there are no other patients involved in the trial that are known to be experiencing similar liver disfunction.
The company plans to provide further information on the ASPIRO programme based on both ongoing data collection and future regulatory status updates.
ASPIRO临床试验旨在评估针对X连锁肌管肌病（XLTM）患者的AT132基因疗法。XLTM是一种罕见的神经肌肉疾病，主要影响男性，导致肌肉无力，严重者可能呼吸困难，因呼吸衰竭而致命。这种遗传性疾病在10岁时的死亡率约为25%。AT132是一种以腺嘌呤相关病毒（AAV）为基础的基因疗法，旨在传递XLMTM中缺失的MTM1基因。
据Audentes说，初步调查结果显示，第三名患者的直接死因是胃肠道出血。死亡的三名患者都在初次给药后的3到4周内开始出现肝功能不全的症状。
Audentes去年被日本制药公司Astellas收购，在披露前两名患者死亡后，于6月被迫搁置了ASPIRO试验。Audentes与ASPIRO研究人员和独立数据监测委员会一起，继续密切监测所有参与研究的患者。Audentes正在调查这三名患者为什么会出现进展性肝功能不全。尽管这项研究目前仍在进行中，但Audentes坚持认为，没有其他参与试验的患者出现类似的肝功能不全。
原文：https://www.pmlive.com/pharma_news/audentes_rare_disease_gene_therapy_programme_indefinitely_delayed_after_third_patient_death_1347266#.X0RTjjlkfZ8.twitter?SQ_DESIGN_NAME=2&
Audentes’ rare disease gene therapy programme delayed after third patient deathThird patient death caused by gastrointestinal bleeding
Audentes Therapeutics has indefinitely delayed plans to seek regulatory approval for its rare disease gene therapy after the death of a third patient involved in a clinical trial of the drug.
This was the third death of a patient involved in the Audentes’ ASPIRO clinical trial, which is evaluating its AT132 gene therapy in patients with X-linked myotubular myopathy (XLTM), a rare neuromuscular disease.
XLTM mainly affects males and causes muscle weakness that ranges in severity from mild to life-threatening. In severe forms of the disease, the weakened muscle make breathing difficult and can lead to respiratory failure. The genetic disorder has a mortality rate of around 25% by the age of ten.
AT132 is an aden-associated virus (AAV) based gene therapy that is designed to deliver the MTM1 gene deficient in XLMTM. According to Audentes, preliminary findings show that the immediate cause of death of the third patient was gastrointestinal bleeding.
The patient ws one of three study participants who had received AT132 at a dose of 3x1014 vg/kg, the higher dose, who subsequently began to demonstrate signs of liver dysfunction within three to four weeks after initial dosing.
The three patients also demonstrated evidence of pre-existing hepatobiliary disease, although over half of the patients enrolled in the study also showed evidence of the same pre-existing conditions.
Audentes, which was bought by Japanese pharma company Astellas last year, was forced to put the ASPIRO trial on hold in June after disclosing the first two patient deaths.
“Audentes, together with the ASPIRO investigators and independent Data Monitoring Committee, continues to closely monitor all patients enrolled in the study. Additionally, Audentes’ investigation into why these three patients developed progressive liver dysfunction is ongoing,” the company said in a statement.
Although the study is currently on hold, Audentes maintained that there are no other patients involved in the trial that are known to be experiencing similar liver disfunction.
The company plans to provide further information on the ASPIRO programme based on both ongoing data collection and future regulatory status updates.
