Creating a cell and gene therapy is complicated, to say the least. To ensure the drug product is safe, effective, and can be manufactured consistently, the FDA and other regulatory agencies worldwide require analytical characterization methods to be established when filing an Investigational New Drug (IND) application and during the clinical trial process.
Although there are over 1,000 clinical trials for cell and gene therapy currently, the analytical methods are still very much a work in progress. On Sept 28-29, Reuters Events hosted the Cell and Gene Therapy USA virtual conference to discuss strategies around cell and gene therapy commercialization, manufacturing, and regulation. All the big names were represented including Pfizer, BMS, Novartis, Moderna, the FDA, and Mission Bio! We organized a roundtable event to discuss if our current analytical methods are sufficient for the innovative treatments in development.
A recent analysis of 149 cell and gene therapy clinical trials identified that 35% of trials report severe adverse events (treatment-emergent serious adverse events, or TESAE)[1]. This is particularly concerning given how complex cell and gene therapies can be to manufacture and characterize. We wanted to use this discussion space to explore how the field was tackling these challenges. The vast majority of our attendees were within the gene therapy space. Here are a few of the discussion points.
The lack of standardization
Given that this space is rapidly evolving with more than 1,000 clinical trials in progress, there is a need to standardize the analytical assays leveraged within the industry. Especially given the safety concerns, should and could more be done upfront, for example expanding the use of in vivo, non-human primate studies, to solidify the preclinical data prior to an IND. While this is not something that can be solved in a simple roundtable, participants questioned whether regulatory agencies have sufficient expertise to understand the increasingly complex technologies required. Given so much in cell and gene therapy is borrowed from biologics and protein therapeutics, there was hope that the field will embrace standard assays to enable the drug developers and their CDMO partners to more effectively and safely create life-changing therapies.
What are the data telling us and how far to look?
The FDA requires multiple, redundant assays to ensure the results are stable, however, the reconciliation of multiple assays with different output poses a challenge. Even relating ddPCR to qPCR data, albeit similar assays, can yield different results. This is amplified when there are many different therapeutics and techniques being used in the cell and gene therapy world, making it harder to identify ways to equate the data and ensure it is fit for purpose. In addition, how far do you want to look? When you don’t know what you don’t know, are there variables we are overlooking because we are not evaluating them? What is going too far? This line of questioning requires a corporate culture that values asking challenging questions and even harder answers to ensure the best path forward fits both the business needs of the company and the safety of patients.
There is a huge disconnect between the number of approved cell and gene therapy products on the market and the number in development — highlighting the constant evolution this field is experiencing. At Mission Bio, we are committed to accelerating the discovery, development, and delivery of advanced therapeutics. Our multi-omics analysis workflow on the Tapestri Platform enables protein and DNA to be assayed from the same single cells. This enables effective product characterization, such as transduction efficiency, genetic change verification (both on and off-target), and vector copy number.
Despite the critical need for better technologies to assess cell and gene therapies, we are hopeful for the future. Many new innovations in biotechnology are being developed to analyze these complex therapeutics better, faster, and for less money. We are committed to providing robust, precise, and reliable single-cell multi-omics capabilities so that the entire field of advanced therapeutics can move forward with confidence.
Interested in more Cell and Gene Therapy conferences? Cell & Gene Meeting on the Mesa is next week! If you are going, be sure to stop by Mission Bio’s exhibitor table and check out the presentation by our CEO, Yan Zhang.
References
- Kuzmin, D.A. et al. The clinical landscape for AAV gene therapies. Nat Rev Drug Discov. 2021 Mar;20(3):173-174.
