In the Age of Individualized Medicine, the U.S. FDA Provides Clarity

Innovative testing and molecular diagnosis have empowered the pinpointing of rare diseases
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Maryland (Precision Vaccinations)

“Advances in scientific knowledge and drug development technology have provided an opportunity for new approaches to drug development, including the development of drugs for the treatment of rare diseases,’ said Patrizia Cavazzoni M.D., Acting Director of the U.S. FDA’s Center for Drug Evaluation and Research.

“In fact, in the past eight years, the FDA has approved more than twice as many drugs for rare diseases, often referred to as orphan drugs, as in the previous eight years.”

Excerpts from Dr. Cavazzoni’s press statement on January 4, 2021, are inserted below.

‘For genetic diseases, recent approaches to testing and molecular diagnosis have allowed us to pinpoint, in some cases, the exact cause of a patient’s condition. For a patient with a rare genetic disease, the development of a drug product tailored to that patient’s specific genetic variant may be possible. 

This is an important advance in treating those with rare genetic diseases, especially those with no adequate therapies available to treat the condition. These sporadic diseases are often rapidly progressing, debilitating, and in many cases, can lead to premature death if left untreated.

Developing these products – also referred to as “n of 1” therapies by some because they are designed for a patient population of one person – brings a set of challenges and considerations not seen with the typical drug development process. 

First, as noted above, the disease is often rapidly progressing, requiring prompt medical intervention. Therefore, development needs to proceed very quickly to have a chance at helping the individual. 

Second, academic investigators may carry out drug discovery and development for these drug products rather than biopharmaceutical or pharmaceutical companies. These investigators may be less familiar with the FDA’s regulations, policies, and practices and less experienced interacting with the FDA. 

At this time, the development of individualized genetic drug products is most advanced for antisense oligonucleotide (ASO) products. 

Therefore, we are taking the first steps in bringing clarity to this emerging area of individualized drug development by releasing new draft guidance on investigational new drug (IND) submissions for individualized ASO drug products.  

The guidance was developed to advise those developing ASO products to interact with and make regulatory submissions to the FDA. The guidance addresses the following points: The path to obtaining feedback from the FDA; The expectations and process for making regulatory submissions to the FDA; Recommendations about the requirement for Institutional Review Board (IRB) review of the protocols within, and How to obtain informed consent.

As also discussed in a New England Journal of Medicine editorial in October 2019, we are fully aware that this new drug-discovery paradigm raises many ethical and societal issues that will need to be addressed throughout the process. 

For example, in these situations, the individuals and their families often function more like drug development collaborators than traditional trial participants. 

Therefore, it is important to discuss with the individual and family members how effectiveness will be measured. It is also vital to ensure that the individual and family members understand the parameters for continuing administration of the investigational drug product before emotions influence decisions and recognize that some investigational drug products may fail, or worse, lead to unforeseen side effects.

The FDA understands that we’ll need to work together with the developers of these drug products to bring them safely to patients, and we are willing to engage as necessary to address the challenges. 

For example, it will be necessary for those developing these drug products to understand further the required data and information that must be submitted to the FDA so that clinical testing can begin. The FDA is continuing to consider and further develop policies to address some of these issues.

We also are optimistic that the development of these individualized drug products may spur gene sequencing, leading to the development of additional individualized drug products for the same disease (though perhaps caused by a different mutation). 

For this approach to drug development, we need to determine – collectively – how to bring these drug products to all who need them effectively. If we have the scientific ability to develop drug products for these rare diseases, we need to find a way to bring them to patients while ensuring there is the right balance of risk to benefit. 

This guidance, which provides clarity on the early development and IND submission process, is the FDA’s first step in working with those who are developing these individualized drug products.

The FDA is an agency within the U.S. Department of Health and Human Services that protect public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices.

PrecisionVaccinations publishes research-based news.