Zoetis Librela® (bedinvetmab injection) and Solensia® (frunevetmab injection)

The Problem

Osteoarthritis (OA) is a painful, progressive, incurable degenerative disease prevalent in dogs and cats. Studies show that as many as 40% of dogs screened for OA had clinical signs, and more than 60% of cats 6 years or older are affected.^1,2

OA is a disease of the joint that impacts the entire wellbeing of the patient, including cognitive function, sleep patterns, sensitivity to environmental stimuli and relationships with humans and other animals.^3,4 Nonsteroidal anti-inflammatory drugs (NSAIDs) were established as a cornerstone of canine OA pain management, yet while these drugs improved the quality of life for millions of dogs, their use has limitations, including:

• Safety concerns — NSAIDs can cause liver and kidney damage and are not well-tolerated by some animals.^5,6
• Availability — No NSAIDs are labeled for chronic OA in the feline species in the United States.
• Compliance — Administering oral medications daily can interfere with the human-animal bond and lapse in compliance.⁷

The Solution

OA is a complex disorder affecting the structure and function of the joint. For dogs, risk factors include poor conformation, genetics, trauma, obestity and age.⁸  The etiology of feline OA is less understood; idiopathic, primary OA is the most common form without an obvious risk factor, while secondary OA results from a risk factor like trauma.⁹  When a risk factor affects a joint, tissue damage triggers the immune system’s inflammatory response. As the condition progresses, the joint is eventually exposed to low-grade inflammation and a chronic catabolic state.

As a consequence of the inflammatory response, many  inflammation mediators and cytokines are released into the joint. One of these is nerve growth factor (NGF), a powerful driver of pain and inflammation. NGF modulates pain and inflammation by interacting with the tropomyosin receptor kinase A (TrkA). TrkA receptors are found on sensory nerves and immune cells.¹⁰ When NGF binds to TrkA, the complex travels to the cell nucleus in the dorsal root ganglion, resulting in peripheral and central sensitization.¹⁰ Further, NGF stimulates the release of inflammatory mediators, substance P and calcitonin gene-related peptide, back to the joint leading to neurogenic inflammation.¹⁰ Other actions of NGF include binding to TrkA receptors on immune cells, causing release of more inflammatory mediators and NGF, angiogenesis and neuronal sprouting. These actions contribute to the cycle of pain, inflammation and joint destruction.¹⁰

The development teams behind Librela and Solensia saw potential in targeting NGF for controlling OA pain in dogs and cats with species-specific anti-NGF monoclonal antibodies (mAbs). Anti-NGF mAbs could sequester excess NGF, preventing its binding to TrkA receptors and therefore reduce the NGF cycle.

The Innovation

The mAbs from one species can induce an immune response when used in another species, so for therapeutic purposes, mAbs need to be species-specific to reduce the risk of reactions to the antibody.

To develop the canine-specific anti-NGF therapy for OA, Zoetis researchers immunized dogs with NGF and tested their serum to determine if anti-NGF mAbs were effectively produced. They collected samples from the dogs who produced anti-NGF mAbs and isolated the B cells that produced the antibodies to NGF. Using advanced technology, large amounts of the monovalent anti-NGF mAbs were produced and purified, creating the master bank, which is used to produce therapeutic batches of the mAbs.

The process to develop feline-specific anti-NGF therapy for OA was similar, but the researchers started by immunizing a mouse rather than a cat. They then replaced parts of the mAbs with feline material until the mAbs were mostly feline.¹⁰

Librela and Solensia are innovative treatment options for controlling OA pain. Given as a once-monthly injection, this route of administration can overcome the challenges of other OA pain medications, such as reduced compliance and disruption in the human-animal bond.⁷

Solensia IMPORTANT SAFETY INFORMATION: For use in cats only. Women who are pregnant, trying to conceive or breastfeeding should take extreme care to avoid self-injection. Hypersensitivity reactions, including anaphylaxis, could potentially occur with self-injection. SOLENSIA should not be used in breeding cats or in pregnant or lactating queens. SOLENSIA should not be administered to cats with known hypersensitivity to frunevetmab. The most common adverse events reported in a clinical study were vomiting and injection site pain. See full Prescribing Information at SolensiaPI.com

Librela IMPORTANT SAFETY INFORMATION: For use in dogs only. Women who are pregnant, trying to conceive or breastfeeding should take extreme care to avoid self-injection. Hypersensitivity reactions, including anaphylaxis, could potentially occur with self-injection. LIBRELA should not be used in breeding, pregnant or lactating dogs. LIBRELA should not be administered to dogs with known hypersensitivity to bedinvetmab. The most common adverse events reported in a clinical study were urinary tract infections, bacterial skin infections and dermatitis. See full Prescribing Information at LibrelaPI.com