The lowdown: Back in July 2007, Targeted Genetics announced that their gene-therapy trial involving intra-articular delivery of tgAAC94 — a recombinant adeno-associated virus serotype 2 (AAV2) vector containing the cDNA for a human tumour necrosis factor receptor (TNFR)–immunoglobulin G1 Fc fusion (TNFR–Fc) gene — was placed on hold while the death of a trial participant was investigated by the National Institutes of Health (NIH) Recombinant DNA Advisory Committee (RAC) (Nature Rev. Drug Discov. 6, 690–691; 2007). When the FDA reviewed the autopsy reports in September it was unclear whether the gene therapy played a role in the participant's death, which was primarily caused by a fungal (Histoplasma capsulatum) infection. The study's independent data safety monitoring board presented findings at the American College of Rheumatology Annual Meeting in November, concluding that the death was not related to tgAAC94. Following these results, the FDA allowed the trial to restart.
On 3 December, the RAC concluded that the opportunistic fungal infection caused the participant to experience a retroperitoneal haematoma and multi-organ failure. They observed that the participant may have been at risk of infection due to her prior long-term use of the TNF antagonist adalimumab (Humira; Abbott Laboratories) and that intra-articular injection of tgAAC94 was unlikely to have contributed to her death.
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