Putting Relaxed NIH, FDA Oversight of Gene Therapies into Perspective

Explaining the Explosion in the Dry Eye Space

The first human gene therapy trial started in 1990, and over the course of that decade a multitude of questions about the safety and efficacy of this approach emerged. In 1999, a patient died during a safety trial of a gene therapy, leading to much greater scrutiny and increased regulatory oversight. Government agencies (including the Food and Drug Administration and the National Institutes of Health), academic institutions, and commercial sponsors diligently worked together to ensure studies that followed had improved safety precautions.

Careful Work Pays Off

“There has been a fair amount of very careful work that has been done since, and that event did reset the field to demonstrate more caution in gene therapy trials,” Karl Csaky, MD, tells OIS Weekly. “And it paid off, because since that tragedy, very few – if any – unanticipated and horrific side effects have happened as a result of a gene therapy trial between 1999 and today.” Dr. Csaky is the T. Boone Pickens director/managing director and CMO of the Clinical Center of Innovation for AMD/Retina Foundation of the Southwest in Dallas.

Move forward to last year, when the FDA approved three gene therapy products, including the first to be delivered in vivo and the first to target a specific genetic condition (retinal dystrophy caused by a mutation in the RPE65 gene) – Spark Therapeutics’ Luxterna. With more than 700 clinical trials underway in a variety of disease states, “it seems reasonable to envision a day when gene therapy will be a mainstay of treatment for many diseases,” NIH Director Francis S. Collins, MD, PhD, and FDA Commissioner Scott Gottlieb, MD, wrote in the New England Journal of Medicine.1

Add to that the advent of genome editing and its possibilities, and the NIH/FDA opting to relax some of the oversight on these types of studies. In fact, “there is no longer sufficient evidence to claim that the risks of gene therapy are entirely unique and unpredictable – or that the field still requires special oversight that falls outside our existing framework for ensuring safety,” Drs. Collins and Gottlieb said. 1

Active in Ophthalmology

At OIS@AAO this year, OIS chair Emmett Cunningham Jr., MD, PhD, MPH, extolled the potential of gene therapy in ophthalmology. “If you follow this space you know gene therapy is active generally, but it’s particularly active in ophthalmology,” Dr. Cunningham stated, noting that 16 companies are pursuing gene therapy programs in the space.

Given the current safety of ongoing gene therapy studies, “it’s reasonable to relax the degree of intense oversight that has involved gene therapy clinical trials,” Dr. Csaky maintains. “I don’t feel that there is any degree of a compromising of safety that will occur by relaxing these requirements. Gene therapy is relatively simple in concept, where you have a vector and put a transgene into the vector, which is then delivered into cells.” The majority of vectors being used are AAV-based, so most of the clinical trial protocols are going to be similar in design, making it easier for the FDA to grant approval for the trial to move forward, he adds.

The NIH/FDA proposed changes (published in the August 18, 2018, Federal Register) seeking to reduce the “duplicative oversight burden by further limiting the role of the NIH and Recombinant DNA Advisory Committee in assessing gene-therapy protocols and reviewing their safety information.”1

Allowing Focus on Next Frontier

These changes “allow the NIH and the FDA now to focus on the next frontier, like gene editing, that is now more in need of oversight to review possible serious questions,” Dr. Csaky says.

For companies involved in gene therapy trials, Dr. Csaky sees little changing in terms of funding.

“Funding is really independent of the FDA’s oversight,” he points out. “The enthusiasm, especially from universities and noncommercial entities that want to fund projects moving forward, may increase even more knowing that the FDA and NIH have the confidence in the therapies.”

For questions about this article, please contact Michelle Dalton at mdalton@dalton-and-associates.com.


  1. Collins FS and Gottlieb S. The next phase of human gene-therapy oversight. N Engl J Med. 2018;379:1392-1395. DOI: 10.1056/NEJMp1810628