G(&)T Without the Headache – Making Nonclinical Safety Studies of Gene Therapy Manageable

Abstract

Since the concept of gene therapy was first discussed in the 1960’s and 70’s, the area has gone through various highs and lows. However, gene therapy is now a therapeutic area experiencing huge investment, development and clinical success. Unsurprisingly, this has led to a surge in nonclinical development of gene therapies spanning small biotech’s and large pharma. Although the goals of nonclinical safety studies of gene therapies are similar compared to traditional biopharmaceuticals, the approach is very different for gene therapies as they are complex biological products. Due to the fast evolving and growing innovation of the gene therapy environment, definitive regulatory guidelines for nonclinical safety assessment do not exist. The available regulatory guidance provides a general framework for the nonclinical safety assessment. Ultimately, the nonclinical safety assessment requires a case-by-case approach that is driven by experience and knowledge of the available regulatory guidelines, previous gene therapy development programmes and product specifications. This presentation will cover the considerations necessary for planning the nonclinical safety assessment of a gene therapy. These considerations include the quality of the test article used, appropriate species selection, bioanalytical assays, toxicity assessments and biodistribution assessments. Nonclinical safety studies of gene therapies that are planned on a case-by-case basis with these considerations and appropriate communication with regulators, where necessary, will typically have a much smoother and efficient process into clinical trials.