The FDA continues to advance new policies, modernize programs and advance opportunities for developing more targeted therapies. Using new technology platforms such as cell and gene therapies and small molecule drugs that target the genomic basis of disease, there are more opportunities to intervene in the underlying mechanisms that cause a disease, and potentially arrest and even reverse its progress.
The scientific opportunities demand that we make sure our policies are as sophisticated as the treatments that are being developed. As the nature of drug discovery and development has become more focused on basic mechanisms of disease, targeted at specific genetic or molecular dysfunctions, science is bringing forward more novel opportunities to meaningfully address human disease.
These new treatments are offering new hope for improved quality of life, and in some cases, improved chances of surviving life-threatening illnesses. To continue this kind of novel innovation, we’re focused on advancing new efforts to modernize the drug development process.
This impressive field of new therapies reflects the fact that more diseases are being redefined based on their molecular underpinning, creating more opportunities to intervene in more diseases and at different points in the disease process. As researchers unlock the molecular basis of disease, they are developing new and more highly effective targets for intervention. At the same time, these new treatments are, in more cases, showing a robust treatment effect—allowing scientists to more quickly bring these products through the development process and demonstrate efficacy and safety in more efficient trials.
One of the most promising ways to make drug development more efficient—while enabling providers and patients to get better information about how a new medicine works—is by developing the science around innovative approaches to the design of clinical trials. These are approaches that can show more quickly and efficiently how a treatment will impact a specific patient population.
FDA identified a need to provide sponsors with guidance on the use of MRD as a biomarker in regulatory submissions. MRD as a general measure of tumor burden has multiple potential regulatory and clinical uses as a biomarker to help with more informed drug development. Depending upon the clinical setting, MRD may reflect a patient’s response to treatment or it may be used as a prognostic tool to assess the risk of future relapse. As such, it may be considered for use to enrich clinical trial populations, or to guide allocation into specific treatment arms in clinical trials and could be developed as a potential surrogate endpoint.
By providing clarity on the regulatory and scientific frameworks for product developers, safe and effective targeted treatments can be identified with scientifically valid tests and ultimately, made available to patients more efficiently. The guidance provides medical product developers with greater clarity on the FDA’s recommendations for researching and developing the next generation of individualized therapies. The guidance discusses an approach for drug developers to enroll patients based on the identification of rare variants into clinical trials for targeted therapies when reasonable scientific evidence suggests the drug could be effective in patients with these genomic findings. The guidance also discusses the evidence needed to demonstrate effectiveness for a variety of molecular subsets within a particular disease. This approach could lead to more consistent development and approval of targeted therapies for patients who are likely to benefit from them.
Understanding the molecular basis of many diseases has paved the way for the development of targeted therapies. For instance, the FDA has already approved a cancer therapy based upon whether the patient’s tumor shows a specific biomarker, rather than based upon the tissue of origin of the tumor—a so-called “tissue agnostic” indication for the drug.
