What is FDA conditional approval?
Our product strategy has always been centered on earning FDA approval. While more challenging, time intensive, and expensive than other approaches, I believe achieving FDA approval is critical to demonstrating the scientific legitimacy of lifespan extension drugs.
Our dog longevity drugs LOY-001, LOY-002, and LOY-003 are all being developed under the FDA Center for Veterinary Medicine’s expanded conditional approval (XCA) pathway. XCA is a new regulatory pathway that allows certain animal drugs to be conditionally approved based on:
Full safety data,
Full manufacturing data, and
Reasonable expectation of effectiveness.
The conditional approval period lasts up to five years while we run the additional studies necessary to demonstrate full efficacy. During that time, veterinarians may prescribe our drug as normal, with full awareness of the conditional nature of the approval. If the drug does not show full efficacy at the end of the conditional period, the drug will be taken off the market.
FDA expanded conditional approval pathway is key to bringing longevity drugs to dogs
One of the underestimated challenges of developing longevity drugs is simply the logistics of demonstrating that a drug definitively extends healthy lifespan. To show a drug is extending lifespan, you must start the dog on the drug sufficiently early and then follow them for the rest of their (hopefully very long!) life. Your study must be large and diverse to not succumb to “noise” — things like variance between dog breeds, healthcare access, environmental factors, and biological luck. As such, our pivotal lifespan extension study STAY will be one of the largest (1,000+ dogs across 55 vet clinics) and longest (~4 years) canine clinical trials ever run.
The conditional approval pathway is intended for animal drugs that address an unmet medical need and require long or complex studies to complete collection of the effectiveness data needed for full approval. It is extremely complex to run a pivotal lifespan extension study, and as such the FDA has determined that LOY-001, LOY-002, and LOY-003 all meet the criteria for using the conditional approval.
For a small company like Loyal, it has been crucial that we have a path to market while running our pivotal lifespan extension studies. The conditional approval allows us to bring new medicines as early as possible to older dogs, who need it most — without risking their safety.
The FDA drug approval process emphasizes safety and efficacy
The drugs your vet prescribes to your dog, like the Librela my senior Rottweiler takes for her osteoarthritis, have been tested extensively for their safety and efficacy before earning FDA approval.
We cannot commercialize any of our products without first earning FDA approval. To do this, we must present extensive data to the FDA in three core areas:
Efficacy — It does what it says it will do; in our case, it extends the lifespan of dogs.
Safety — It’s proven safe for dogs, and any side effects are well-understood and documented.
Manufacturing — It can be manufactured at a consistently high quality, at scale.
What data we’ll have at conditional approval
Full Target Animal Safety
Full Chemistry, Manufacturing, and Controls
Reasonable Expectation of Effectiveness (RXE)
Conditional approval has the same strict safety and manufacturing quality requirements as full approval. For a drug that will be given to relatively healthy dogs, like LOY-002, the safety bar is especially high.
Reasonable expectation of efficacy is just what it sounds like — the process consists of shorter studies that prove reasonable expectation that the drug will have the full efficacy you expect. Loyal’s accepted RXE package for LOY-001 included over 2,000 pages of evidence and analysis from various sources, including scientific literature, observational studies, and interventional studies.
Upon approval, the FDA will publish the Freedom of Information (FOI) summary, which will overview the key safety and efficacy data. This is intended for dog owners and veterinarians to educate themselves on the scientific backing of the drug and make an informed choice on whether to prescribe.
An overview of the regulatory process to conditional approval and — eventually — full marketing approval
What data we won’t have at conditional approval
Pivotal, randomized, double-blinded, placebo-controlled study showing lifespan extension.
Should the FDA grant LOY-002 conditional marketing approval, veterinarians will be able prescribe the drug. At this point, we won’t yet have full lifespan extension efficacy data. The study to get this data (STAY) will run in parallel with the conditional approval period.
We must complete and analyze the STAY study (estimated 2029) and submit to the FDA to convert our conditional approval into full approval. If we do not complete the study, or if we do not show pivotal lifespan extension in the treated dogs, the drug will be taken off market — as it should be.
Regulatory innovation
As with all medicines, the key balance is risk:reward. I’m grateful to the FDA that the conditional approval pathway exists. It allows new companies like Loyal to develop innovative drugs and get them into the hands of veterinarians to better the lives of both dogs and their owners. We take the responsibility of developing a new drug incredibly seriously and will never push forward a drug that our scientists and veterinarians do not truly believe will extend the healthy lifespan of our beloved dogs.
Resources
Learn more about expanded conditional approval and the FDA: