Laboratory safety evaluations of izenivetmab, a caninized anti-nerve growth factor monoclonal antibody, for three-month alleviation of osteoarthritic pain in dogs.

Canine osteoarthritis is a degenerative joint disease causing impaired mobility, chronic pain, and is a significant factor in euthanasia decisions in dogs. Managing pain is one of the main objectives of medical treatment of osteoarthritis. Nerve growth factor (NGF), a critical mediator of nociception, is an analgesic therapeutic target. Izenivetmab, a caninized monoclonal antibody (mAb), binds to NGF and limits its downstream signaling. As part of the pre-approval safety assessment of izenivetmab, three laboratory studies were conducted in adult laboratory Beagle dogs. Assessments were conducted on general health, body weight, body temperature, food consumption, clinical pathology, toxicokinetics, and anti-drug antibodies (ADA). Study 1 additionally included electrocardiography, neurologic and ophthalmic evaluations, radiographs of joints, routine histopathology and enhanced histopathological evaluation of joints, nervous, and immune tissues. Study 2 evaluated safety of izenivetmab at higher dose multiples, dosed at an increased frequency (monthly), and included additional joint and neurological evaluation. Study 3 was a functional immune assessment. Izenivetmab was well-tolerated when dosed once every three months for three total doses of up to 0.6 mg/kg (6X, six times the upper range of the clinical dose), and when dosed monthly for four total doses of up to 12 mg/kg (120X). Treatment-emergent immunogenicity was observed in 1/24 (4.2%), 2/24 (8.3%), and 1/16 (6.25%) of izenivetmab treated dogs in Studies 1, 2, and 3 respectively, without safety impact. The results from these studies support the safety of izenivetmab in dogs when administered subcutaneously at the intended dose (0.05-0.1 mg/kg) once every three months.