Longer lives for bigger dogs? Loyal earns third RXE acceptance from the FDA
At Loyal, our mission is to develop the first FDA-approved drugs indicated to preserve quality of life, delay frailty, and extend lifespan. Today, we’re excited to announce we’re one step closer to making that a reality: LOY-003, our drug program for large and giant-breed lifespan extension, has achieved Reasonable Expectation of Effectiveness (RXE). This is the third time that Loyal has demonstrated to the FDA that a drug can likely extend a dog’s healthy lifespan.
As a scientist at Loyal, our group is responsible for the biological work that informs our drug programs and ultimately goes into our RXE submissions. We operate at the critical intersection where aging biology meets drug discovery and development. This intersection is where ideas and hypotheses about how dogs age, and how to potentially extend their lifespans, leave the theoretical and are translated into potential therapies. Unlike traditional animal health companies and other longevity biotechs, we are developing drugs that explicitly aim to extend the healthy lifespans of our canine companions.
For more on our approach to aging → loyal.com/our-approach
Why LOY-003?
There is significant variance in the lifespans of dogs, and lifespan is very closely correlated with a dog’s size. At the most extreme, big dogs like Great Danes have an average life expectancy of 6-8 years, whereas small dogs like Chihuahuas can live up to 20 years. This is a phenomenon unique to dogs and likely a consequence of historic inbreeding.
The same biological pathway that causes big dogs to grow large and fast ultimately accelerates their aging and makes them die sooner.
Scientific evidence suggests this discrepancy is driven by two key hormones: growth hormone (GH) and insulin-like growth factor-1 (IGF-1).1-2 Both are well known regulators of size, but also play an important role in dogs’ lifespans and healthspans. Big dogs can have anywhere between ~2-30X as much IGF-1 as medium and small dogs, with higher levels being associated with 1) the final adult size of dogs but also 2) significantly shorter lifespans.3 Put simply, the same biological pathway that causes big dogs to grow large and fast ultimately accelerates their aging and makes them die sooner.
LOY-003 is a once daily oral tablet focused on addressing this “big dog, short life” problem many dog owners and vets are all too familiar with. Similar to LOY-001, which was the first drug to achieve an RXE acceptance for lifespan extension in any species, LOY-003 reduces GH and IGF-1 levels with the aim of preserving quality of life and extending lifespan in large- and giant-breed dogs. The FDA now agrees that LOY-003 can reasonably be expected to be effective at achieving this.
From the lab to the real world
The impact of GH and IGF-1 on body size and lifespan isn’t exclusive to dogs. It is among the most conserved regulators of lifespan ever discovered. In 1993, Dr. Cynthia Kenyon published a paradigm-shifting study showing that mutating the gene that regulates insulin/IGF-1 signaling in roundworms doubled their lifespan.4 Since then, decades of research have shown that lowering GH and IGF-1 signaling reproducibly leads to longer lives and delays the onset of certain chronic diseases across species. LOY-003 targets that same, conserved pathway via a therapeutic intervention.
At Loyal, we’re building on decades of research on aging and lifespan extension and are doing something novel by forging the regulatory and clinical path to translate the science on lifespan out of the laboratory. This has the potential to create a new category of therapeutics: preventive medicines developed to explicitly help our dogs live longer, healthier lives. LOY-003’s RXE is another signal that we’re on the right path to being able to do what we set out to achieve from the beginning.
What’s next
This represents the third time the scientists, veterinary, and regulatory professionals at Loyal have achieved RXE for a unique drug with lifespan as the primary indication: LOY-001 and LOY-003 for large dogs and LOY-002 for senior dogs. Our team is always pushing forward on the science, regulation, and commercialization of the first longevity drugs for dogs, and we’re excited to celebrate this accomplishment as we continue to advance our portfolio towards hopeful approval.
Even as we look to bring our first drugs to market, our science team will continue working at the intersection of aging biology, research, and drug discovery to really understand the biological processes happening in our dogs as they age. By uncovering and understanding new and specific aging pathways, we can identify new therapies and ways to help all dogs live longer, healthier lives.
References
Greer KA, Hughes LM, Masternak MM. Connecting serum IGF-1, body size, and age in the domestic dog. Age (Dordr). 2011 Sep;33(3):475-83. doi: 10.1007/s11357-010-9182-4. Epub 2010 Sep 24. PMID: 20865338; PMCID: PMC3168604.
Sutter NB, Bustamante CD, Chase K, Gray MM, Zhao K, Zhu L, Padhukasahasram B, Karlins E, Davis S, Jones PG, Quignon P, Johnson GS, Parker HG, Fretwell N, Mosher DS, Lawler DF, Satyaraj E, Nordborg M, Lark KG, Wayne RK, Ostrander EA. A single IGF1 allele is a major determinant of small size in dogs. Science. 2007 Apr 6;316(5821):112-5. doi: 10.1126/science.1137045. Erratum in: Science. 2007 Jun 1;316(5829):1284. PMID: 17412960; PMCID: PMC2789551.
Selman C, Nussey DH, Monaghan P. Ageing: it's a dog's life. Curr Biol. 2013 May 20;23(10):R451-3. doi: 10.1016/j.cub.2013.04.005. PMID: 23701689.
Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R. A C. elegans mutant that lives twice as long as wild type. Nature. 1993 Dec 2;366(6454):461-4. doi: 10.1038/366461a0. PMID: 8247153.