Progressing Towards Regulatory Approval of Veterinary Therapies Targeting Aging
Veterinary medicine is typically less impeded by FDA regulatory costs than human medicine. A cynic would note that the publicity-related incentives operating on FDA staff and leadership are quite different in these two cases, with a great deal more attention given by the media to matters regarding human medicine. With the relative costs being what they are, a number of entrepreneurs in the longevity industry chose to work towards veterinary therapies targeting mechanisms of aging. One of those companies, Loyal, here reports on progress towards the FDA essentially agreeing to a regulatory framework for therapies targeting aging rather than specific diseases. On the human side of the house, you might recall that the primary analogous effort is the TAME trial and the lobbying surrounding it, a very expensive and slow-moving process that has yet to come to fruition.
Loyal's approach involves adjusting a mechanism of metabolism that operates differently in large dogs versus small dogs, and which may provide a meaningful contribution to the well-known lifespan differences between breeds of different sizes. This treatment is thus intended for large dogs only. The FDA may or may not be considering the details of the specific approach used to be an important factor in allowing treatment of aging in dogs. The regulators may or may not reject a similar path to approval for other approaches, such as implementations of SENS-style repair of molecular damage. It remains to be seen as to whether a following company will be able to point to Loyal's regulatory progress and expect the FDA to approve a different treatment intended to slow or reverse aging in dogs, or other animals, without picking a specific disease to focus on. Still, that is the goal!
Loyal was only a few months old and about five people when we decided to begin by targeting the abnormally short lifespan of large breed dogs with a drug program we code-named LOY-001. LOY-001 extends lifespan in part by reducing IGF-1 to levels seen in smaller-breed dogs. The IGF-1 axis is one of the most well-studied longevity pathways. In model organisms from C. elegans to mice, reducing IGF-1 extends healthy lifespan, and increasing IGF-1 shortens healthy lifespan. In humans, certain centenarians have been shown to have genetically lower levels of IGF-1.
Today, I'm so proud to announce that Loyal has earned what we believe to be the FDA's first-ever formal acceptance that a drug can be developed and approved to extend lifespan. In regulatory parlance, we have completed the technical effectiveness portion of our conditional approval application for LOY-001's use in large dog lifespan extension. As there was no established regulatory path for a lifespan extension drug, we had to design from scratch a scientifically strong and logistically feasible way to demonstrate efficacy of an aging drug. This process took more than four years, resulting in the 2,300+ page technical section now approved by the FDA. It included interventional studies of LOY-001 in an FDA-accepted model of canine aging and an observational (no-drug) study of 451 dogs.
Our interventional studies with LOY-001 showed that the drug improved clinically-relevant aging parameters. We assessed these in laboratory studies using a dog model that represents accelerated aging. We then correlated those results with quality of life scores in the observational study, as independently measured by dog owners, and health outcomes as measured by veterinarians. This was key to show that the biological benefits of the drug are linked to clinically relevant outcomes. From our data, the FDA believes LOY-001 is likely to be effective for large dog lifespan extension in the real world. Once we satisfactorily complete safety and manufacturing sections and other requirements, vets will be able to prescribe LOY-001 to extend the lifespan of large dogs while we complete the confirmatory pivotal lifespan extension study in parallel.