Another Patient Dies Following Treatment with Astellas' Experimental Gene Therapy

Astellas_Yuriko Nakao/Getty Images

Yuriko Nakao/Getty Images

A patient treated with Astellas Pharma’s experimental gene therapy for patients with X-linked Myotubular Myopathy (XLMTM) has died after reports of a serious adverse event following treatment with AT132 earlier this month. The patient’s death marks the fourth during clinical trials over the past two years.

The patient, who died on Sept. 9, is the only patient treated with the gene therapy in the ASPIRO trial following the lifting of a clinical hold in December. The clinical hold was placed on the study after Astellas and Audentes, which developed the asset, reported multiple deaths of trial patients who received the gene therapy. Three patients died following complications with sepsis and gastrointestinal bleed, all of which are consequences of liver failure.

The latest patient was treated with a lower dosing level; however, weeks after administration of the therapy, Astellas said abnormal liver functions were reported. Astellas voluntarily paused the study ahead of a regulatory agency’s decision. The U.S. Food and Drug Administration (FDA) later placed a clinical hold on the study.

When Astellas first announced the serious adverse event, the company said the patient has a history of intermittent cholestasis, which impacts bile flow from the gallbladder. According to the company, Prior to dosing, the patient received the green light to participate in the trial following an ultrasound that showed normal liver functions with normal bilirubin levels.

This morning, Astellas said the cause of death is still pending.

Japan-based Astellas said it is gathering relevant clinical information that will be included in the investigation regarding other serious adverse events observed to date in the ASPIRO trial. Despite a fourth death in the ongoing study, Nathan Bachtell, M.D., senior vice president at Astellas and head of Gene Therapy, extended condolences to the trial patient’s family. Despite the death of the latest patient at the lower dosing level, Astellas does not appear ready to scrap the experimental gene therapy.

“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,” Bachtell said in a statement.

After disclosing the serious adverse event earlier this month, Bachtell expressed confidence that AT132 has the potential to be a successful treatment for XLMTM, a life-threatening neuromuscular disease that is typically characterized by extreme muscle weakness, respiratory failure and early death. As BioSpace previously reported, Bachtell said after the discloser that any severe adverse event needs to be viewed “both individually and in the context of the broader program as we move forward.”

According to Astellas, it will review its contents and have further dialogue with regulators on the path forward.

AT132 is an AAV8 vector that contains a functional copy of the MTM1 gene. The company believes AT132 targets skeletal muscle and increases myotubularin expression in those tissues after the administration of a single dose. AT132 has been granted Regenerative Medicine and Advanced Therapy designation from the UFDA. It has also been granted Rare Pediatric Disease, Fast Track and Orphan Drug designations.

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