The Food and Drug Administration (FDA) considers aging to be a natural process. This makes it difficult to get FDA approval for drugs that seek to slow or reverse the biological process of aging. Instead, drugs intended to target aging must target a disease that often results from the aging process in order to demonstrate efficacy and gain approval.
But there is growing consensus and effort among scientists to convince the FDA that aging itself should be classified as a disease and an appropriate target for drug development.
This could be a major milestone for not just industry, but society. If the FDA is swayed, the resulting regulatory shift could mean approval of drugs or treatments that slow or reverse the aging process generally, before a patient develops disease.
Researchers who view aging as a medical condition aren’t referring only to the inevitable passage of time. Instead, they view aging as a process of deterioration of our structure and function at the cellular level; the hallmark characteristics of which are genomic instability and damage to our DNA.
And the World Health Organization (WHO) supports this view – WHO describes the process of aging as “… the impact of the accumulation of a wide variety of molecular and cellular damage over time.”
Advanced chronological age is widely acknowledged to be the biggest risk factor for developing disease, but the process of aging itself results in fragility and mental decline, even absent any disease. As the WHO describes it, aging is “a gradual decrease in physical and mental capacity.” In fact, the WHO recently included “ageing associated decline in intrinsic capacity” as a disease code in the 11th edition of International Classification of Diseases (ICD).
This is particularly significant, because diseases are conditions that can be treated, or are at least worthy of the effort, which implies that the WHO views aging-related decline as a treatable condition.
The FDA likely will revisit this issue, as scientific pressure mounts to declare aging a drug target. Part of the problem is that the FDA needs more guidance to determine how “aging” should be measured, and needs to see evidence that targeting “aging” biomarkers actually has a beneficial effect.
In addition to industry pressure, the FDA faces pressure from Congress to clarify the regulatory pathway for emerging regenerative therapies. Seven years have passed since the FDA gave its blessing for the Targeting Aging with Metformin (TAME) clinical trial, the first trial to target the effects of aging. TAME is a double blind, placebo-controlled, multi-center study designed to evaluate whether the diabetes drug Metformin can protect against age-related conditions such as cancer, dementia or cardiovascular disease in non-diabetic study participants. The goal of the trial is to establish an indication for aging, which the American Federation of Aging Research refers to as a “proof of concept” that aging is an appropriate drug target. In this way, the goal of TAME is more political than scientific.
The scientific community continues to discuss its next steps, including potential aging-related biomarkers that should serve as acceptable targets for regenerative therapies. The acceptance of biomarkers to represent the aging process is not as big of a regulatory jump as it might seem. For example, the FDA recently expressed a willingness to consider biomarkers for the identification of early-stage Alzheimer’s disease.
We may be a few well-designed studies away from FDA acceptance of aging as a drug target, particularly as researchers bridge the divide between the TAME target and better-accepted disease targets. The looming possibility of a regulatory pathway for anti-aging therapies warrants an evaluation of how a new regulatory pathway will affect the market.
Here’s what we could expect:
- The market for regenerative therapies will expand to nearly the entire adult population. Regenerative therapy companies targeting the biological process of aging are currently limited to addressing specific diseases or medical conditions to obtain FDA approval. Drugs or therapies that get to market are typically limited in approved use for one disease; approval for additional diseases often comes years later.
- Removal of the disease-specific regulatory barriers would make regenerative therapies available as preventative care solutions. According to David Sinclair, a professor of genetics at Harvard Medical School and leader in the field of regenerative medicine, work to develop medicines that could prevent many diseases is going far slower than it should be, because aging is not recognized as a medical condition.
Simply put, therapies that target the process of aging itself will enjoy a nearly unlimited market, compared to therapies with the same mechanism that target a single disease.
- “There is little doubt that approval of drugs and therapies to treat aging in general would have a significant impact on research funding,” says Mark Mirkin, a corporate and securities lawyer at Rimon PC, the firm where I work. “For example, the venture capital industry would be very receptive to entrepreneurial ventures addressing diagnostics, therapeutics and devices directed toward the broad markets resulting from an FDA-approved aging-related disease sector. Start-ups, especially university spin-outs, with federal grant funding will be attractive seed capital financing opportunities for individual angel investors, angel funds and family offices, etc. … Early-stage venture capital funds, hungry for exciting new pathways, will follow. Such financing is certain to attract attention from strategic investors, including Big Pharma.”
Lastly, let’s talk about the prospect of democratized access to preventative care and better manufacturer-clinician communication in the process.
Disease-specific drug approvals force clinicians to grapple on their own with the off-label use of a drug in addressing any disease or medical condition not approved by the FDA. Except to warn of contraindications, manufacturers cannot communicate with clinicians about off-label use. As a result, many patients outside the class for whom a drug was approved are not able to receive the drug until years have passed and millions more dollars have been spent on clinical trials in a disease-by-disease evaluation.
FDA approval of regenerative therapies for the treatment of aging ultimately would put important safety information in the hands of community clinicians, allow access to reimbursement through health insurance, and therefore put the therapy within reach of the general population.
It’s an unfortunate truth of health care in America that wealthy patients have better access to both preventative and disease care than less-privileged patients. This economic dichotomy would be alleviated, to a degree, with a regulatory shift to target aging as a treatment indication.
Amy Baker is a partner in the Orlando office of Rimon PC, with clients in the life sciences industry, including legal issues regarding emerging technologies, regulatory compliance and Food and Drug Administration and Federal Trade Commission regulations.