Astellas has seen a fourth death of a young child in its gene therapy trial of an experimental drug gained through the pharma’s $3 billion buyout of biotech Audentes.
The so-called ASPIRO trial had been testing the gene therapy AT132 in a rare neuromuscular disease, X-linked myotubular myopathy (XLMTM), but has been hit by three deaths from that test, leading to a clinical hold (but this was lifted by the FDA late last year), and then, earlier this month, Astellas was forced to pause work on the test.
This came after it saw abnormal liver function test results in a patient who received the low dose. The patient had a history of intermittent liver disease, but the organ appeared to be normal at the start of the study.
Tuesday morning, the Japanese pharma said this patient has now died. It did not give a cause of death.
Going into 2020, Astellas planned to file for approval of AT132 in a rare neuromuscular disease by the end of the year. Instead, three deaths linked to liver failure among the 17 patients who received the high dose of the AAV8 vector gene therapy led to a clinical hold.
The FDA lifted the hold in December after Astellas dropped the high dose, though this latest death coming from a low-dose patient will raise further safety concerns. Astellas said in its latest update that the FDA has now issued a new clinical hold for the trial.
“Astellas is gathering the relevant clinical information and incorporating such information into the ongoing investigation regarding other serious adverse events observed to date in the ASPIRO trial,” the company said in a statement.
“This was the first and only participant dosed following the December 23, 2020, release of the earlier FDA clinical hold.”
Having already switched to the low dose, which contains less than half the vector genomes per kilogram of body weight of the high dose, it is unclear whether Astellas has room to go lower. The AT132 dose at which the latest serious adverse event occurred is the lowest tested in the clinical trial, although other gene therapies have worked at lower doses.
The latest setback raises further doubts about Astellas’ chances of generating a return on its $3 billion takeover of Audentes. In April, Astellas took a $540 million impairment loss related to AT132, and the continued woes of the gene therapy could have further financial consequences.
“On behalf of Astellas, we extend our deepest sympathies to the participant's family,” said Nathan Bachtell, M.D., senior vice president and head of gene therapy, medical and development, at Astellas. “We will investigate and review all findings with our independent data monitoring committee, our expert liver advisory panel and the Aspiro site investigators. We remain committed to the development of AT132 and the XLMTM patient community.”