astellas gene therapeutics

Rare Daily Staff

Astellas Pharma said that a fourth child died in its trial of AT132, its experimental gene therapy in patients with X-linked myotubular myopathy, a rare, neuromuscular disease, after developing a serious adverse event.

The child died September 9 and the company said the cause of death is still pending. He was the only patient dosed following the U.S. Food and Drug Administration’s lifting of a clinical hold on the study at the end of December.

XLMTM is a serious, life-threatening, rare neuromuscular disease that is characterized by extreme muscle weakness, respiratory failure, and early death. Mortality rates are estimated to be 50 percent in the first 18 months of life. For those patients who survive past infancy, there is an estimated additional 25 percent mortality by the age of 10. XLMTM is caused by mutations in the MTM1 gene that lead to a lack or dysfunction of myotubularin, a protein that is needed for normal development, maturation, and function of skeletal muscle cells. The disease affects approximately 1 in 40,000 to 50,000 newborn males.

Astellas took over the AT132 program following its $3 billion acquisition of Audentes. AT132 is an AAV8 vector containing a functional copy of the MTM1 gene, for the treatment of XLMTM. AT132 may provide patients with significantly improved outcomes based on the ability of AAV8 to target skeletal muscle and increase myotubularin expression in targeted tissues following a single intravenous administration. The preclinical development of AT132 was conducted in collaboration with Genethon.

ASPIRO is a two-part, multinational, randomized, open-label ascending dose trial to evaluate the safety and preliminary efficacy of AT132 in XLMTM patients less than five years of age. Primary endpoints include safety (adverse events and certain laboratory measures) and efficacy (assessments of neuromuscular and respiratory function). Secondary endpoints include the burden of disease and health-related quality-of-life, and muscle tissue histology and biomarkers.

“On behalf of Astellas, we extend our deepest sympathies to the participant’s family, said Nathan Bachtell, 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.”  

Photo: Nathan Bachtell, senior vice president and head of gene therapy medical & development at Astellas.  

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