Monoclonal antibodies on the horizon in veterinary medicine

Two veterinary companies are making strides toward introducing monoclonal antibody therapy to the field of veterinary medicine. Nexvet Biopharma, a companion-animal-focused veterinary company with headquarters in Dublin, Ireland, is currently testing an osteoarthritis treatment, and Aratana Therapeutics, a pet therapeutics company in Kansas City, Kansas, was recently granted licensure from the U.S. Department of Agriculture (USDA) for a therapy targeting B-cell lymphoma in dogs.

Monoclonal antibodies, molecules that are engineered to mimic natural antibody proteins in the immune system, are increasingly being used in human medicine. Nexvet's first monoclonal antibody, NV-01, is in safety and effectiveness studies in the United States and Europe for the control of pain associated with osteoarthritis in dogs. Results are expected at the end of 2015, with preliminary data presented at the 2014 ACVIM Forum and in the American Journal of Veterinary Research.1-2

NV-01 works by inhibiting nerve growth factor (NGF), which acts on pain-sensing nerve fibers to increase their excitability and increase the sprouting of new nerve fibers into inflamed tissues and is elevated in the joints of dogs with osteoarthritis. Human monoclonal antibodies targeting NGF have been extensively studied in humans and have been shown to be highly effective in managing osteoarthritic pain in patients, the company says.

Nexvet uses a process called “PETization” to generate its monoclonal antibody therapies. This process utilizes proprietary libraries of genetic information and algorithms to make sure that key amino acid sequences are recognized as “self” or “native” by the target species' immune system. This reduces the chance of undesirable immune reactions, the company says.

This process also allows Nexvet to create new therapies rapidly; these therapies are customized to a particular species and designed to feature all the advantages typical of monoclonal antibodies: potency, safety and a prolonged elimination half-life-often giving therapeutic effects for weeks after a single injection, the company says. No adverse effects have been observed in any of Nexvet's studies of NV-01 to-date.

Nexvet is also working on two other biologic therapies, including NV-02, a monoclonal antibody therapy similar to NV-01 but for cats, and NV-08, a fusion protein that is a tumor necrosis factor inhibitor for the treatment of chronic inflammatory diseases, including atopic dermatitis, in dogs.

Aratana's USDA-approved AT-004 is  a canine-specific monoclonal antibody that targets CD20 as an aid in the treatment of B-cell lymphoma in dogs. B-cell lymphoma is a common cancer in dogs, Aratana representatives say, and can progress quickly if left untreated. Nearly all dogs suffer significant side effects from chemotherapy and ultimately relapse, leaving a significant need for new treatment options, Aratana says.

Aratana's portfolio also includes AT-005, a monoclonal antibody targeting CD52 as an aid in the treatment of T-cell lymphoma in dogs, which received a conditional license from the USDA in January 2014.  The company has also submitted AT-014, a novel cancer immunotherapy for canine osteosarcoma, for a product license with the USDA.

References

1. Lascelles D. Efficacy of canine anti-nerve growth factor antibody for the alleviation of degenerative joint disease-associated pain in dogs. ACVIM presentation of late-breaking abstracts, June 7, 2014.

2. Webster RP, Anderson GI, Gearing DP. Canine Brief Pain Inventory scores for dogs with osteoarthritis before and after administration of a monoclonal antibody against nerve growth factor. American Journal of Veterinary Research. 2014, 75:532-535. tinyurl.com/lhun2q3