The DNA double-helix was first postulated to be the building blocks of life by Watson and Crick in a seminal paper in 1953. Their discovery spawned a revolution in molecular biology in the 65 years that have followed, and led to the understanding of human biology, human disease and our manipulation of it. However, just several years ago, even with significant advances in the field, the idea of gene therapy to treat or cure a disorder was thought to be a distant science fiction dream. Well, welcome to the future.
Three different gene therapy products have been approved by the FDA in the last year. With gene therapies in pursuit for autoimmune diseases, heart disease, cancer, HIV/AIDs as well as genetic disorders, and continued advances with new genetic manipulation technologies such as CRISPR, the FDA is expanding how to handle gene therapy as a new and innovative approach to medicine. On July 11, 2018, Scott Gottlieb, MD, Commissioner of the FDA, announced new FDA guidances aimed at standardizing the approach companies should take as they develop and progress gene therapy programs. The FDA acknowledges that challenges exist for gene therapy that haven’t existed for prior medicines and have committed to modernizing their approach to gene therapies to accommodate these new challenges.
The FDA’s main purpose is to ensure that products that reach the market are both safe and effective. Even with the 3 initial successes in treating disorders with gene therapy, there is a lot to learn, especially about the long-term impacts like durability, side-effects and potential off-target effects, which will only come with time. For gene therapy development programs long-term uncertainty is a new dilemma, but the FDA is taking a fresh look at how to accommodate that not everything can be known in a reasonable time-frame for a market approval request without stifling development. Robust long-term follow-up can be addressed by requiring continued development for safety and efficacy optimization with additional clinical trials after market approval. Regardless of how FDA chooses to address long-term follow-up, they remain committed to promoting safe and effective product development through a regulatory path that maintains the gold standard in gene therapy as it has for other types of medicines.
One of the new draft guidances is directed at gene therapy for rare disorders, which would apply to Rett Syndrome. More than 25 million Americans are affected by a rare disease, 80% of them are caused by single-gene disorders, half of rare diseases affect children, and almost none have effective treatments. The guidance outlines the FDA’s current thinking on non-clinical studies (non-human studies) manufacturing, and clinical trial designs, and a draft version has been provided to the public for comment to ensure every angle of gene therapy development has been considered and the guidance will be thorough enough to encompass as much gene therapy development as currently possible. In the draft guidance FDA acknowledges some of the unique issues facing rare disorders such as a limited patient population, feasibility, safety, and how to measure efficacy, and the guidance is intended to assist companies in how to approach these key issues.
In the face of uncertainty and the unique known and unknown challenges posed by gene therapy the FDA is not only present, but has embraced this innovative field and is committed to its success, as clearly stated by Dr. Gottlieb, “Gene therapy represents one of the most promising opportunities for developing highly effective and even curative treatments for many vexing disorders. Some of these products are almost certainly going to change the contours of medical practice, and the destiny of patients with some debilitating diseases.”
We are in a new era of medicine. Are you ready?