For immediate release:
Declaration of:

Author of the declaration

Leadership role

Acting Director – Center for Drug Evaluation and Research

Deputy Director of Operations Center – Center for Drug Evaluation and Research | CDER

Patrizia Cavazzoni MD

Advances in scientific knowledge and drug development technology have offered the possibility of new approaches to drug development, including the development of drugs for the treatment of rare diseases. These advances have contributed to an increase in the development and approval of drugs for the treatment of rare diseases in recent years. In fact, in the past eight years, the U.S. Food and Drug Administration has approved more than twice as many drugs for rare diseases, often referred to as orphan drugs, than in the previous eight years.

For genetic diseases, recent approaches to screening and molecular diagnosis have enabled us to identify, in some cases, the exact cause of a patient’s disease. For a patient with a very rare genetic disease, the development of a drug product tailored to that patient’s specific genetic variant may be possible. This is an important breakthrough in the treatment of people with very rare genetic diseases, especially those for whom there are no adequate therapies available to treat the disease. Often, these very rare diseases progress quickly, are debilitating, and in many cases can lead to premature death if left untreated.

The development of these products – also referred to as ‘n in 1’ therapies by some because they are designed for a one-person patient population – brings a set of challenges and considerations that are not seen with the process. typical drug development. First, as noted above, the disease often progresses rapidly, requiring prompt medical intervention. Therefore, development has to happen very quickly to have any chance of helping the individual. Second, drug discovery and development for these pharmaceuticals can be done by academic researchers, rather than biopharmaceutical or pharmaceutical companies. These investigators may be less familiar with FDA regulations, policies, and practices, and less experienced in interacting with the FDA.

At present, the development of individualized genetic pharmaceuticals is the most advanced for antisense oligonucleotide products (ASO). Therefore, we are taking the first steps to clarify this new area of ​​individualized drug development by publishing a new draft of the New Investigational Drug Submissions (IND) guidelines for individualized ASO pharmaceuticals.

The guidelines were developed to advise those who develop ASO products on an approach to interacting with the FDA and making regulatory submissions to the FDA. The guide covers the following points:

  • The approach to obtaining feedback from the FDA,
  • The expectations and process for submitting regulatory submissions to the FDA,
  • Recommendations on the requirement for Institutional Review Board (IRB) review of protocols within and
  • How to obtain informed consent.

As also discussed in a New England Journal of Medicine October 2019 editorial, we are fully aware that this new paradigm of drug discovery raises many ethical and societal questions that will need to be addressed throughout the process. For example, in these situations, individuals and their families often function more as collaborators in drug development than as traditional participants in trials. Therefore, it is important to discuss with the individual and family members how effectiveness will be measured. It is also important to ensure that the individual and family members understand the parameters of the continued administration of the investigational drug before emotions influence decisions, and to recognize that some investigational drug products may or may not fail. , worse yet, lead to unintended side effects.

The FDA understands that we will need to work with the developers of these drugs to get them safely to patients, and we are ready to engage as needed to meet the challenges. For example, for those who are developing these pharmaceuticals, it will be important to better understand the required data and information that must be submitted to the FDA so that clinical trials can begin. The FDA continues to review and further develop policy to address some of these issues.

We are also optimistic that the development of these individualized pharmaceuticals could stimulate gene sequencing that leads to the development of additional individualized pharmaceuticals for the same disease (although possibly caused by a different mutation). For this approach to drug development, we need to determine – collectively – how to effectively get these drugs to all who need them. If we have the scientific capacity to develop drugs for these rare diseases, we need to find a way to deliver them to patients while ensuring the right balance between risks and benefits. This guide, which clarifies the process of early IND development and submission, is the FDA’s first step in working with those who develop these individualized pharmaceuticals.

The FDA, an agency of the US Department of Health and Human Services, protects public health by ensuring the safety, efficacy, and safety of human and veterinary drugs, vaccines and other biologicals for human use, and medical devices . The agency is also responsible for the safety and security of the food supply, cosmetics, dietary supplements, products emitting electronic radiation and the regulation of tobacco products.

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