To date, the U.S. Food and Drug Administration (FDA) has approved four gene therapy products, which insert new genetic material into a patient’s cells. The agency expects a boom in gene therapy product approvals in the coming decade as evidenced by the more than 900 investigational new drug (IND) applications for ongoing clinical studies in this area. The FDA recently issued a press release announcing they believe this will provide patients and providers with increased therapeutic choices. Consequently, the agency announced the release of a number of important policies including: six final guidelines on gene therapy manufacturing and clinical development of products and a draft guidance, Interpreting Sameness of Gene Therapy Products Under the Orphan Drug Regulations.
Overview: Guidance for Gene Therapy Manufacturers
The six final guidance issued today provide the agency’s recommendations for product developers on manufacturing issues and recommendations for those focusing on gene therapy products to address specific disease areas. The six guidance documents incorporate input from many stakeholders and take a significant step toward helping to shape the modern structure for the development and manufacture of gene therapies. The agency is issuing this suite of documents to help advance the field of gene therapy while providing recommendations to help ensure that these innovative products meet the FDA’s standards for safety and effectiveness.
Gene Therapy May Requires Robust Post-Marketing Surveillance
The scientific review of gene therapies includes the need to evaluate highly complex information on product manufacturing and quality. In addition, the clinical review of these products frequently poses more challenging questions to regulators than reviews of more conventional drugs, such as questions about the durability of response, and these questions often can’t be fully answered in pre-market trials of reasonable size and duration. For some gene therapy products, therefore, although they have met the FDA’s standards for approval, we may need to accept some level of uncertainty around questions of the duration of the response at the time of marketing authorization. Effective tools for reliable post-market follow up, such as post-market clinical trials, are going to be key to advancing this field and helping to ensure that our approach fosters safe and innovative treatments.
Current Thinking on Interpretation of Sameness of Gene Therapy Products
The draft guidance on interpreting sameness of gene therapy products under the orphan drug regulations provides the FDA’s proposed current thinking on an interpretation of sameness between gene therapy products for the purposes of obtaining orphan-drug designation and eligibility for orphan-drug exclusivity. The draft guidance focuses on how the FDA will evaluate differences between gene therapy products when they are intended to treat the same disease. As laid out in the draft guidance and our regulations, the agency’s determination will consider the principal molecular structural features of the gene therapy products, which includes transgenes (the transferred gene) and vectors (the vehicle for delivering the transgene to a cell).
With the large volume of products currently being studied, gene therapy product developers have asked the agency important questions about orphan-drug designation incentives to develop products for rare diseases with very small patient populations. The draft guidance has potential positive implications both for product developers and patients by providing insight into the agency’s most current thinking on the sameness of products, and thus, not discourage the development of multiple gene therapy products to treat the same disease or condition. For patients, this policy could help lead to the development and approval of multiple treatments, creating a more competitive market with choices. We encourage stakeholders to provide their comments.
FDA Encourages Drug Developers to Utilize Expedited Programs
In sum, these policy documents are representative of efforts to help advance product development in the field of gene therapy. We will continue to work with product innovators, sponsors, researchers, patients, and other stakeholders to help make the development and review of these products more efficient, while putting in place the regulatory controls needed to ensure that the resulting therapies are both safe and effective. We also encourage developers of new gene therapy products to make full use of our expedited programs available for products intended to address unmet medical needs in the treatment of serious or life-threatening conditions. These programs include breakthrough therapy designation, regenerative medicine advanced therapy designation, and fast track designation, as well as priority review and accelerated approval. Developers should pursue these programs whenever possible to help bring the benefits of important advances to patients as soon as possible. We believe our work will help advance innovations in a way that assures their safety and effectiveness, provides new therapeutic choices to patients and providers and continues to build confidence in this novel and emerging area of medicine.
Call to Action: See the link for associated guidance information.