Four Tips for Successful Development of Cell and Gene Therapies

Developing a cell or gene therapy (CGT) involves a range of regulatory considerations and challenges. Emily Marden and Jaclyn Fonteyne point to some key factors that are currently the focus of FDA attention and may merit consideration by sponsors early in the development process.

The FDA’s Center for Biologics Evaluation and Research (CBER) has indicated that it would like to pick up the pace of approvals of CGT approvals, which is good news for sponsors. Sponsors would also be well advised to note the following factors which can help in a successful pathway towards approval:

  1. Manufacturing Strategies for Clinical and Commercial Supply. It has been widely acknowledged – including by the FDA – that manufacturing is a key challenge for the approval and widespread availability of CGTs. Manufacturing issues – including the transition from clinical supply to commercial supply, and ensuring quality – have led to a number of clinical holds and delays in approval. The FDA has repeatedly made it clear – including in new draft guidance published this month – that it is open to innovative approaches in manufacturing CGTs and that it acknowledges that manufacturing processes may be subject to modification even after approval. Notably, the new draft guidance focuses on establishing “a robust framework” for managing such manufacturing changes, one which incorporates risk management, product stability, and comparability studies. Sponsors should be aware of the FDA’s expectations and work collaboratively and transparently with the agency to mitigate the risk of manufacturing issues posing an obstacle to the development and/or approval of a CGT.
  2. Potential for Accelerated Approval. CBER has recently signalled that the FDA’s Accelerated Approval pathway – which allows for accelerated approval based on a surrogate endpoint or endpoints – may provide an avenue for speeding up the availability of CGTs. CBER also indicated that, for such products, extended follow-up of clinical subjects might suffice as confirmatory evidence which could lead to a full approval. This is a potentially significant development, one which indicates that sponsors should – early in the development process – carefully consider surrogate endpoints for discussion with the agency.
  3. Availability of Orphan Drug Exclusivity. A seven year period of marketing exclusivity may be available for CGTs treating a “rare disease or condition”. The scope and availability of such exclusivity for CGTs has long been the subject of discussion and debate. In 2021, the FDA published a final guidance document on this issue with respect to gene therapies, which addressed certain scenarios. However, significant questions remain about the scope and blocking effect of orphan exclusivity with respect to cell Sponsors should therefore carefully monitor the agency’s current position when setting expectations on orphan exclusivity.
  4. Attention to Long-Term Safety Throughout Development. The FDA has released a series of guidance documents covering numerous aspects of CGT development. Although they address differing phases of development, these guidance documents collectively make it clear that the long-term safety of a proposed therapeutic must be considered throughout every step of preclinical and clinical development. Building such questions into testing protocols should therefore be a focus of early stage strategy.

This post is as of the posting date stated above. Sidley Austin LLP assumes no duty to update this post or post about any subsequent developments having a bearing on this post.