Loyal veterinary company employees propose changes to an FDA pathway to speed approval of drugs that reduce the risk of age-related diseases

Loyal veterinary company employees propose changes to an FDA pathway to speed approval of drugs that reduce the risk of age-related diseases

In a commentary published on October 23 in GeroScience, employees and/or shareholders of Loyal Animal Health proposed linking early measurable indicators to changes in an FDA application pathway. Their proposal concerns geroprotectors, drugs intended to reduce the risk of age-related diseases and death. An accelerated approval pathway would become available only after an early indicator had been shown to predict a clinical outcome.

To establish that a drug reduces the risk of death or extends life, a trial must follow participants for years until enough cases of disease and deaths have occurred. Such a trial requires thousands of people and a large budget. For long-established drugs, market exclusivity may expire before results are available.

The authors’ first step is a surrogate endpoint: an early measurable indicator whose relationship to a later clinical outcome must be confirmed. This would allow a drug to be evaluated before the trial has collected sufficient data on all-cause mortality.

In the Nature Aging hierarchy of outcomes, these indicators rank below death, serious disease, and loss of function. The Loyal commentary considers the next step: which regulatory pathway to offer once an indicator has passed this validation.

The authors propose modifying 505(b)(2), a type of new drug application that can draw some of its supporting evidence from studies the applicant did not conduct and for which it has no right of reference. Their proposed version would allow accelerated approval of already approved drugs with evidence of an all-cause mortality benefit across several diseases and an established body of safety data. Full approval would still require the main clinical development program.

The authors suggest GLP-1 receptor agonists and SGLT2 inhibitors as the first test cases. These two drug classes are already used to treat diabetes, heart failure, and chronic kidney disease. The choice reflects evidence of reduced all-cause mortality in these patient groups and accumulated experience with their safe use.

The authors draw their procedural model from expanded conditional approval for animal drugs. The FDA allows an animal drug to be marketed once its safety has been established and there is a reasonable expectation of effectiveness, while the company collects the evidence needed for full approval. Conditional approval is renewed annually for up to five years.

Loyal itself is conducting the STAY trial in older dogs, with the primary aim of testing whether treatment extends lifespan. This veterinary experience explains why the authors use an existing FDA pathway as a model for their proposed human drug pathway.

An early indicator shortens the wait for results, existing drug data reduce the amount of work that must be repeated, and accelerated approval could generate revenue to fund a long-term study of clinical outcomes.