With every major advancement in the field of aging biology, humankind is one step closer to turning back the clock and restoring our youth. In our previous longevity blog, we highlighted several novel therapeutics that have shown promise in extending lifespan and increasing healthspan (the amount of time spent in life free of disease) in animal models. If science is advancing us towards the “fountain of youth”, why are there no FDA approved anti-aging therapies on the market? In this second installment of our “Longevity Series”, we discuss regulatory, scientific, and practical hurdles that scientists in the longevity community must overcome to bring their new drugs to the general population. 

According to the CFR - Code of Federal Regulations Title 21, the FDA defines a disease as “damage to an organ part, structure, or system of the body such that it does not function properly”. Currently, the FDA does not recognize aging as a disease, but rather considers it a natural process. Herein poses a conundrum, the FDA approves drugs on an indication-specific basis to treat a specific disease, however, aging is not considered a disease in the eyes of the FDA. Given the FDA’s stance on not defining aging as a disease, scientists do not have a regulatory pathway forward for the approval of their therapies or drugs designed to specifically target aging. The tides may be shifting in favor of scientists, as other regulatory agencies, namely the World Health Organization, take a different stance on whether aging is a disease. In fact, “Ageing associated decline in intrinsic capacity” was recently added to the 11th Edition of the International Classification of Diseases (ICD), the universal coding system for diseases and medical conditions. There is potential, that with the addition of aging into the ICD, that the FDA may revisit their stance on defining aging as a disease rather than a natural process.

Given the FDA’s stance on not defining aging as a disease, scientists do not have a regulatory pathway forward for the approval of their therapies or drugs designed to specifically target aging. The tides may be shifting in favor of scientists, as other regulatory agencies, namely the World Health Organization, take a different stance on whether aging is a disease.

While hope may be on the horizon for a regulatory pathway for anti-aging therapies, scientific hurdles still pose an obstacle before the general population will have access to these drugs. For example, a well-defined and clinically validated biomarker that accurately defines aging is still lacking. This is in stark contrast to other diseases that have symptoms with clinically validated biomarkers to evaluate efficacy of therapeutics. The field of aging not having a clinically validated biomarker of aging poses a significant barrier, because the FDA would have no way of assessing the efficacy or success of anti-aging drugs in clinical trials. Scientists are investing tremendous amounts of resources at identifying and characterizing a clinically validated biomarker specific to aging. Once candidate biomarkers of aging are identified, a scientific consensus will need to be reached as to the most clinically relevant ones that can be measured in clinical trials. Until that consensus is reached, how do scientists plan to advance their scientific discoveries? One potential strategy is to design clinical trials around the use of surrogate biomarkers/endpoints (a biomarker that is used in substitute of a clinical biomarker). These surrogate biomarkers/endpoints consist of laboratory or physical measurements that have not yet been proven to be a direct measurement of clinical benefit. In fact, the FDA has a history of advancing drugs to the market through the use of surrogate biomarkers/endpoints (Table of Surrogate Endpoints That Were the Basis of Drug Approval or Licensure). This type of clinical trial design may hold viability in advancing anti-aging therapeutics to the market.

Beyond the scientific and regulatory hurdles associated with gaining market approval for anti-aging therapies, there are practical obstacles that must be overcome. In particular, the design and costs of conducting clinical trials specifically aimed at reversing aging pose a substantial barrier in the longevity community. Clinical trials are aimed at getting novel therapies to treat diseases approved. This entails enrolling patients with the disease of interest into the clinical trial and determining how well a new drug works at reversing or curing that disease. As stated above, aging is not currently considered a disease by the FDA. As such, the design of clinical trials to study the impact of anti-aging therapies would consist solely of healthy participants. This is not an ethical problem, as healthy participants are enrolled in Phase I clinical trials. However, for the FDA to approve a therapy intended for use in the general population rather than population defined by the presence of a disease, clinical trials would have to demonstrate not only is the therapy effective at reversing the aging process but is nearly completely safe as well. Recruiting only healthy participants for a clinical trial results in a need for a higher number of participants than what is traditionally needed for a clinical trial in order to detect differences between groups. Additionally, the question arises of how long an anti-aging trial should be conducted to observe an appreciable difference in lifespan extension. The potentially extended nature of the design coupled with the large number of participants needed to observe differences in lifespan extension trials poses significant cost barriers in the longevity field.

Scientific progress is continually being made in understanding the aging process and how to manipulate it in our favor. We have described some of the hurdles scientists within the longevity field have to overcome to commercialize their scientific discoveries. In the next installment of our blog series, we will detail some of the innovative ways scientists are traversing the regulatory landscape in an effort to combat aging and age-related diseases in the United States.