Pharmaceutical companies call for greater flexibility in assessing the toxicity of AAV-mediated gene therapy

The question of the duration of clinical and biological monitoring after gene therapy remains under debate, particularly beyond 18 months:

• a survey was conducted among thirteen laboratories involved in clinical gene therapy protocols using adeno-associated viruses (AAV« adeno-associated virus » , ou virus adéno-associé est un petit virus à ADN simple brin. Il fait partie de la famille des Parvoviridae et appartient au genre des Dependovirus. La particule virale est constituée d’un brin d’ADN de polarité positive ou négative protégé par une capside. La taille moyenne d’une particule d’AAV et de 18 à 22 nm. Les AAV sont les seuls parvovirus non autonomes. Lorsqu’on emploie « rAAV » , il s’agit du virus AAV recombinant, c’est-à-dire qu’il a été modifié pour devenir un vecteur (et n’est donc plus virulent).),
• out of 24 programmes listed, the vast majority of adverse effects were noted and documented in the first three months after administration,
• and extending monitoring to longer periods was not always dictated by regulatory considerations.

The authors therefore argue for a relaxation and harmonisation of the rules in this area, which would reduce the costs of toxicity studies and increase the attractiveness of AAV-mediated gene therapies.

Nonclinical toxicity study duration in AAV gene therapy development: Evidence from industry survey supports adequacy of short-term assessments. Assaf BT, Edwards D, Berens SJ et al. Mol Ther Methods Clin Dev. 2025 Nov.