We are one step closer to two drugs to increase longevity in dogs. One of them could be available as early as late 2025.

A recent announcement by the company Loyal, shared exciting news that they received RXE approval from the FDA for their code-named drug LOY-002.

RXE stands for Reasonable Expectation of Effectiveness, and is a big part of the conditional approval process to get a new animal drug approved in the US. RXE allows a drug to move forward based on preliminary data that suggests it will likely be effective.

This FDA conditional drug approval process allows companies to bring medications to market and to patients sooner, while conducting longer effectiveness studies.

The drugs must still meet the same safety and manufacturing standards as drugs that are fully approved. To stay on the market beyond the five-year conditional approval period, Loyal must demonstrate full efficacy — in this case lifespan extension — in a large study.

The FDA’s Expanded Conditional Approval steps (image Loyal.com)

This is pretty cool news.

This will be the first longevity drug on the market.

Ever.

But this isn’t Loyal’s only RXE approval!

They are also developing a longevity drug specifically for large breed dogs, that targets the mechanism that causes large and giant dogs to live shorter lives, compared to small dogs. That drug is called LOY-001. That was the first FDA RXE approval for a longevity drug.

Is this a big deal?

Heck, ya.

The FDA is essentially saying, “We’ve looked at your research, and we think you’re onto something real here.”

This has never been done before for any species (including humans)
It validates the scientific approach of targeting aging as a treatable condition
It potentially opens the pathway for similar approaches in human medicine

The sciency nerd in me is getting chills.

The senior dog owner in me wishes this had come along 5 years ago…

LOY-002 and the STAY Study

The LOY-002 research (the STAY study) is the largest clinical study for drug approval in veterinary history. There are 1,000 client-owned dogs enrolled, through various vet clinics in the US.

The actual drug in question is hush-hush while they are still in the pre-approval stage.

But we know what aging problem they are targeting.

Loyal has stated that this drug will increase healthy lifespan through improving metabolic health.

“The one thing that has consistently shown lifespan and healthspan extension in any complex organism is caloric restriction. A successfully completed lifespan extension study in dogs, carried out by Purina in the 1990s, had a 25% caloric restriction in Labradors and showed a two-year lifespan extension, and an approximate two-year delay in osteoarthritis and cancer incidence.

LOY-002 emulates what we believe is biologically activated when a dog is calorically restricted. The dogs don’t lose weight and it’s not a weight loss drug – it activates a downstream mechanism. “

-Quote from Loyal founder and CEO Celine Halioua

Why Metabolic Dysfunction Matters

Metabolic dysfunction is the silent enemy of healthy aging in dogs (and people too).

As we get older, the ability to regulate blood sugar, process insulin, and maintain healthy fat distribution declines, leading to a cascade of health problems.

Metabolic dysfunction, and resulting whole body inflammation, is thought to be the underlying cause of so many of the chronic diseases of people and pets.

This dysfunction is characterized by:

Insulin Resistance: When cells don’t respond properly to insulin, blood sugar remains elevated, forcing the pancreas to work overtime.
Chronic Inflammation: Dysfunctional fat tissue releases inflammatory compounds throughout the body.
Cellular Damage: Poor metabolic health accelerates cellular aging and reduces the body’s ability to repair itself.
Disease Progression: Metabolic dysfunction increases risk for diabetes, cancer, cognitive decline, and heart problems.

Now we know, in general terms, what LOY-002 is trying to slow or reverse.

How Does LOY-002 Work?

LOY-002 is a Caloric-Restriction Mimetic.

Caloric restriction mimetics fool your body’s sensors into thinking you’re eating less, shifting cells from growth to maintenance mode while triggering protective stress responses.

These drugs essentially trick your metabolism into operating as if you’re fasting—activating cellular cleanup systems that remove damaged components and recycle them, similar to how spring cleaning refreshes your home.

These mechanisms help explain why these drugs might slow aging – they basically trigger the same beneficial cellular responses as eating less, without the hunger!

We know that caloric restriction and fasting leads to longer lives. For more info on how this was proven, read my article here. (HINT- my favorite study of all time, done with my favorite breed).

A new study from the Dog Aging Project showed that once a day feeding was associated with less disease in dogs. Read the article here.

Can We Make Any Guesses About LOY-002?

With a little detective work (read wild *ss guess), knowing the primary pathway activated by caloric restriction is AMPK, I think the drug will be an AMPK activator like metformin.

Metformin is one of the most commonly prescribed drugs in human medicine. It is the number 1 choice to treat type 2 diabetes.

How this might relate to a longevity drug:

It was found that Metformin users with diabetes often live as long as or longer than people without diabetes, which is surprising since diabetes typically shortens lifespan
Multiple studies have found associations between metformin use and reduced risks of cancer, heart disease, and cognitive decline
The TAME (Targeting Aging with MEtformin) trial is currently studying whether metformin can extend healthy lifespan in humans

Is LOY-002 likely to be metformin?

No, it probably isn’t.

It is easier to get approval for a new drug, than to repurpose an old one.

Plus, as an older drug, metformin can be produced as a generic drug. A drug company makes their largest profits by patenting a drug, and having exclusive rights to manufacture and sell for the first 15- 20 years. After this time, other companies can produce and sell it, undercutting the original producer.

It is possible that LOY-002 is a synthetic derivative of metformin, created specifically for dogs, with a longer action and less side effects. LOY-002 is a once daily pill—metformin that needs to be given more frequently.

Interestingly, the drug may be made from natural plant compounds that activate the same pathway.

Possibilities include:

Berberine– from many plants, used in traditional medicine
Pterostilbene– a very healthy component of blueberries and grapes

I am interested to see, when more information comes out about LOY-002 later this year, if I was wildly off-base!

What does this mean for pet owners?

With any luck, the drug will be granted conditional approval this year and be available for vets to prescribe to dogs in the USA.

It will likely be for dogs over 14 lbs, and older than 10 years (like the dogs in the STAY study), as a once a day flavoured chewable.

What can we do now to improve our dog’s health?

Do we need to wait for a drug to be approved to get the benefits of improving metabolic health?

Of course not!

Simple steps to take:

Get your pet to a Healthy Weight – read article about weight loss in pets
Get out and get some exercise – read article about how activity trackers use is changing pet health (and ours too!)
Routine Veterinary Care to catch problems early
Nutritional Supplements: Omega 3 Fatty Acids can decrease the inflammation associated with metabolic dysfunction and improve lipid metabolism
Stress Management – environmental enrichment, positive training and exercise are great
Medication Review: If your dog is on long-term medications like corticosteroids, consult with your vet about the risks of insulin resistance and explore alternative treatments if possible.
Good Nutrition – avoid excessively high fat and high glycemic carb diets
Consider Once a day feeding– read article about this feeding technique in dogs

I will update my newsletter readers with any news on the approval process of this drug and Loyal’s other longevity drug for big dogs! Don’t miss out-subscribe to the free weekly newsletter.