Sept. 7 Quick Takes: Parsing the BioMarin gene therapy hold

Though evidence is lacking that tumorigenic potential of AAV vectors in mice translates to humans, FDA placed a clinical hold on the Phase I/II Phearless trial of AAV5 gene therapy BMN 307 from BioMarin Pharmaceuticals Inc. (NASDAQ:BMRN) after mice developed liver tumors in a preclinical study. In an immunodeficient mouse model of phenylketonuria (PKU), six of seven animals treated with the highest dose level of the AAV5 vector delivering the phenylalanine hydroxylase (PAH) gene, 2x1014, developed liver tumors.

The hold comes four days after FDA’s Cellular, Tissue and Gene Therapies Advisory Committee held a meeting discussing the safety of AAV gene therapies highlighted the potential for AAV vectors — particularly AAV5 — to integrate into the mouse genome and lead to liver cancers; humans and non-human primates lack a key AAV integration site present in mice, and the vectors haven’t yet led to liver cancer in the larger animals and humans...