Astellas said Tuesday that a participant in a study of its experimental gene therapy AT132 who developed a serious adverse event (SAE) has now died, bringing the number of fatalities in the trial to four. The company, which paused dosing in the Phase I/II ASPIRO study earlier this month, indicated that the cause of death is still pending.
The trial of AT132 for patients with X-linked myotubular myopathy (XLMTM) had been placed on clinical hold by the FDA in 2020 following the deaths of two participants, with a third death announced in August of last year. Following the SAE earlier this month, Astellas said that the FDA again placed the trial on hold, but the company still awaiting written confirmation from the agency.
Once it receives the official letter, the drugmaker said it plans more discussions with regulators on a path forward for the treatment, which it acquired through its purchase of Audentes Therapeutics for around $3 billion. Astellas noted that the latest death occurred in the only patient dosed after the earlier FDA clinical hold was lifted in December 2020 with study protocol changes. These included reducing the dose to less than half the level given to the three previous participants who had died.
Nathan Bachtell, head of gene therapy, medical and development at Astellas, said "we will investigate and review all findings with our independent data monitoring committee, our expert liver advisory panel and the ASPIRO site investigators." AT132 comprises an AAV8 vector containing a functional copy of the MTM1 gene (for related analysis, see ViewPoints: Astellas' big Audentes bet in peril of a timely fizzle).
Last week, the FDA placed a clinical hold on BioMarin Pharmaceutical's Phase I/II Phearless study investigating the experimental AAV5-phenylalanine hydroxylase gene therapy BMN 307 in adults with phenylketonuria after liver tumours were seen in preclinical studies (see ViewPoints: BioMarin bookends FDA's gene therapy safety meeting).
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