EXCERPT:
REGENXBIO reported a clinical hold following detection of an AAV vector genome integration event associated with overexpression of PLAG1, a proto-oncogene. The finding adds to a growing body of evidence that integration risk in AAV programs warrants deeper characterization.
CONTENT:
REGENXBIO has disclosed a clinical hold on one of its AAV programs following a troubling finding: preliminary genetic analysis of a tumor detected an AAV vector genome integration event associated with overexpression of PLAG1, a proto-oncogene.
AAV vectors have long been considered episomal — meaning they generally don’t integrate into the host genome. That assumption has been the basis for decades of safety arguments in favor of AAV over lentiviral approaches. Events like this one challenge that narrative and will likely intensify regulatory scrutiny of long-term genotoxicity assessments in AAV programs.
For sponsors and CROs working in this space, the practical implication is clear: integration site analysis and long-term follow-up data are no longer optional considerations for late-phase AAV programs. They are becoming table stakes for regulatory discussions.