Dr Clive Glover, director, Strategy, Pall Corporation discusses recent industry developments surrounding cell and gene therapies and why safety is a key priority for this treatment area.
Gene therapy
In January 2020, the US Food and Drug Administration (FDA) published a series of seven guidances regarding cell and gene therapy. These have not come too soon, given some much-publicised regulatory rejections. For example, the FDA turning down the Biologics License Application of BioMarin valoctocogene roxaparvovec for severe haemophilia A. Following relatively recent European regulatory revisions, the FDA guidances, as usual, apply to the manufacture as well as the development and clinical trials of drugs. A major challenge of cell and gene therapy developers is balancing clinical considerations with logistical demands such as manufacture. The evolution of a robust manufacturing process that complies with the FDA guidance is reliant in part on the technical innovations by companies like Pall, a global supplier of filtration, separations, and purification products.
In the case of high-dose adeno-associated virus (AAV) gene therapies, which have been associated with hepatic and systemic inflammatory toxicities, there has been discussion on shifting focus from finding safer ways of delivering high doses of AAVs to re-engineering AAVs to eliminate entirely the need for high doses. This can be done by processes such as directed evolution, allowing them to better target the required tissue. If the therapy is more tissue-specific, not as high a dose would be needed. However, this can have a dramatic effect on manufacturing capacity with manufacturing titres dropping by as much as 100-fold with AAVs adapted to hybrid or artificial serotypes. Thus, the drug development focus diverts from clinical to manufacturing effectiveness.