AKL Research and Development partner with world-leading animal health company to test novel osteoarthritis drug in dogs

Stevenage, UK, 28 July 2020AKL Research and Development (AKLRD), a pharmaceutical company developing an investigational osteoarthritis (OA) medicine, has signed an agreement with one of the world’s top five animal health companies to fund the development of its next-stage clinical trial in canine OA. Osteoarthritis is the most common form of arthritis in dogs, affecting approximately a quarter of the population.[i]


Under the terms of the agreement, AKLRD’s partner will fund a study in dogs with naturally occurring OA. The study will compare the efficacy and efficacy duration of the investigational drug APPA to the standard of care for treating canine OA. Currently, dogs with OA are usually treated with non-steroidal anti-inflammatory drugs (NSAIDs), such as meloxicam and carprofen. Common side effects of veterinary NSAIDs include vomiting, diarrhoea, not eating/eating less and lethargy while some may also be associated with gastrointestinal ulcers/perforations, and liver and kidney toxicity.[ii] 


David Miles, AKLRD CEO, says: “Just like humans, millions of dogs suffer intolerable pain and disability because of OA and the current treatments just aren’t as effective or as well tolerated as they need to be. We already know from previous canine studies that APPA reduces pain and has an excellent tolerability profile but this exciting new partnership will allow us to go one stage further and assess sustainability of response.”


APPA is an oral, patented, fixed-dose combination of two synthetic secondary metabolites of plant origin–apocynin (4-hydroxy-3-methoxyacetophenone) and its isomer paenol (2-hydroxy-4-methoxy-acetophenone). As an NFkB and Nrf2 gene transcription modulator, APPA provides its anti-inflammatory effect by harmonising the cross-talk between these two signalling molecules in the inflammatory process.


The randomised study will assess pain and duration of response as the primary endpoint. The potential for APPA to improve outcomes in dogs with OA by inhibiting inflammatory pain pathways and reducing cartilage degradation is supported by in vitro data and histologic assessment conducted in a rodent OA model.[iii]


Secondary endpoint assessment includes adverse events, quality of life, pharmacokinetics analysis and biomarkers that may enable potential identification of factors predictive of response at treatment onset, or that correlate with response magnitude.


Two separate studies on dogs have already been carried out by researchers at the University of Vienna. The first, an 11-week cross-over study of 32 canines diagnosed with established, naturally occurring OA, showed that APPA provides significant symptom relief in clinical canine OA.[i] A follow-up, five-week study of 60 dogs with OA compared APPA to the standard of care drug, meloxicam. It concluded that daily oral administration of APPA was effective as a stand-alone alternative to NSAIDs in dogs with naturally occurring OA. Significant benefits were also seen for APPA over meloxicam in orthopaedic examination as well as in lameness and function scores.[ii]

APPA’s complete lack of inhibition of COX enzymes supports the observation that vomiting occurred less in the APPA arm of this study.[iii]

The results will inform the pivotal clinical trial design and it is AKLRD’s working assumption that a 26-week field study would complete the regulatory requirements for commercialisation. If the study and future testing is successful, AKLRD estimates that APPA would be well placed to capture a significant share of the global canine OA market, which is estimated to be worth $3billion by 2028.[iv]




For more information, please contact:


David Miles

AKL Research & Development

E: dm@aklrd.com

Sarah Wolf

The Difference Collective

T: 07747 733 216

E: sarah.wolf@thedifferencecollective.com



About APPA

·       APPA is a patented fixed combination of two synthetically produced, synergistic, secondary metabolites of plant origin, which exerts its anti-inflammatory effect by modulating the pathways of intracellular signalling molecules, NFkB and Nrf2. Related to innate immune responses, APPA also inhibits the formation of neutrophil extracellular traps (NETs).

·       APPA is unique because it directly affects inflammation at its source by re-balancing NFkB and Nrf2. APPA regulates rather than blocks the immune response, allowing the body to maintain host defence mechanisms.



·       AKL Research & Development (AKLRD) Ltd’s primary focus is inflammatory diseases, particularly those related to the disruption of the immune system, such as OA.

·       It identifies secondary metabolites of plant origin with proven efficacy and safety, which are then synthesised before undergoing standard pharmaceutical clinical development. This innovative approach greatly increases the chances of success, while reducing the likelihood of unexpected side effects.

·       AKLRD is based at the Stevenage Bioscience Catalyst, Stevenage, Herts UK. http://www.aklrd.com



[i] Glasson S, Larkins N. APPA provides symptom relief in clinical canine osteoarthritis. Osteoarthritis and Cartilage. 1, S287, April 01, 2012. doi.org/10.1016/j.joca.2012.02.494

[ii] Larkins N, King C. Effectiveness of apocynin-paeonol (APPA) for the management of osteoarthritis in dogs: comparisons with placebo and meloxicam in client-owned dogs. Matters. 2017. DOI: 10.19185/matters.201608000001201608000001

[iii] AKLRD data on file

[iv] Cision. PR Newswire. NSAIDs to Treat Arthritis Canines Through 2028; Stem Cell Therapies to Invigorate Canine Arthritis Treatment Market. 6 August 2018. https://www.prnewswire.co.uk/news-releases/nsaids-to-treat-arthritic-canines-through-2028-stem-cell-therapies-to-invigorate-canine-arthritis-690140291.html [Accessed 15 July 2020]


[i] American College of Veterinary Surgeons (ACVS).

https://www.acvs.org/small-animal/osteoarthritis-in-dogs [Accessed 15 July 2020]

[ii] Veterinary Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). US Food & Drug Administration (FDA). https://www.fda.gov/animal-veterinary/product-safety-information/veterinary-non-steroidal-anti-inflammatory-drugs-nsaids [Accessed 15 July 2020]

[iii] Glasson S, Bendele A, Larkins N. APPA provides disease modification in preclinical osteoarthritis. Planta Med 2012; 78 – PI215 DOI: 10.1055/s-0032-1320902