Skip to content

The FDA’s Response to an Increase in the Development of Gene and Cell Therapies: What It Means for Sponsors

In the last two decades, our understanding of the mechanisms behind human disease paired with significant innovation in complementary technologies has empowered our industry to develop treatments for a wide variety of previously untreatable conditions. Two such treatment categories are cell and gene therapy: intersecting fields of research that target DNA or RNA. While both therapies aim to modify genetic material, gene therapy uses DNA to manipulate a patient’s cells to compensate for abnormal genes or to make a beneficial protein, and cell therapy utilizes transfusion or implantation of human cells to repair or replace those that have been damaged. Differences between the two non-withstanding, early successes in this area have made believers in the potential of cell and gene therapies out of many of us in the industry.

As a result, the FDA has observed an unprecedented increase in the number of cell and gene therapy products entering the early stages of development. In a recent statement on new policies to advance the development of safe and effective cell and gene therapies, the FDA reports that it only expects these numbers to continue to grow. In fact, the agency predicts that by 2020, over 200 cell-based or directly administered gene therapy INDs will be submitted per year and that by 2025 it will be approving ten to twenty of these types of therapeutics per year. To further accelerate these promising innovations, the FDA is planning review group expansions that will allow for the evaluation of more cell and gene therapy product applications. It will also be focused on developing new policy guidance and making advancements in its established drug development framework in the coming year to specifically address cell and gene therapies, covering the following topics:

The Accelerated Approval Pathway
The accelerated approval pathway offers a more expedited route to approval for new treatments addressing substantial unmet medical needs. The FDA plans to work with sponsor companies to maximize the use of the regenerative medicine advanced therapy (RMAT) designation and accelerate approval for gene therapies that address serious and life-threatening diseases with a meaningful therapeutic advantage over existing treatment options. For gene therapy in particular, many of the associated risks tend to manifest in the long-term; therefore an accelerated approval pathway can get these much-needed therapies to patients faster, but also gives the FDA more oversight of postmarket follow-up studies with the goal of developing a larger data set to identify and address their potential risks in a timely fashion – data that may not be obtainable in pre-market trials alone.

Clinical Guidance Documents
The FDA has laid out plans for a series of clinical guidance documents that relate to a variety of topics around active product development. For example, guidance documents that discuss the development of gene therapy products for inherited blood disorders like hemophilia, and those that dive into the issues related to development of gene therapies for neurodegenerative diseases. Guidance in these areas and more will allow all those involved in the development process to work in a more standardized way, promoting the efficient advancement of safe, effective cell-based and gene therapy medicines that give hope to patients who’ve previously had no treatment options.

Advances in Manufacturing
Another area of guidance the FDA plans to elaborate on are the parameters for introducing new advances in manufacturing, in particular those aimed at more efficient development and application of cell therapies like CAR-T without necessitating new cost-prohibitive clinical investigations. This guidance will focus on ways to help ensure the safety and efficacy of the manufactured end product using existing technologies and methods and limited clinical bridging studies. In fact, the FDA announced that it will be holding a public meeting in the coming months to discuss ways to expedite clinical bridging studies when manufacturing process changes are made.

Gaining a Biologics License Application (BLA)
To ensure everyone has an efficient pathway by which to compliantly obtain new BLAs, the FDA intends to issue guidance outlining an innovative trial design in which individual researchers who follow a common manufacturing protocol can pool their clinical data, in turn developing a more robust data set to secure a BLA. This will help smaller sponsors and academic investigators gain the scale to conduct clinical trials on their own – a novel approach that brings our industry together around a common goal.

The industry certainly agrees that cell and gene therapies hold tremendous promise, but with their novelty also come new ambiguities and risks. The FDA has voiced its commitment to proactively addressing these challenges and providing the resources that sponsors and CROs need to safely, effectively, and compliantly accelerate development of these high-potential therapeutics.

Like the FDA, BioAgilytix is also expanding to better support our clients’ cell and gene therapy studies. We are excited to be on the forefront of innovating new best practices and methods to meet the evolving needs of the industry. Our deep NAb assay capabilities and vast experience with a variety of viral vectors, including common adeno-associated viruses (AAVs) and Lentivirus, give us the necessary insight to support this new wave of product innovations. The planned guidance from the FDA in 2019 will only help to further inform our next steps as more and more cell and gene therapy projects enter our laboratories.

Gene Therapy for Cancer Treatment Concept Cancer therapy with T-cell and DNA