Background: Nerve growth factor (NGF) plays a key role in osteoarthritis (OA) pain. Although anti-NGF therapies are effective in canine OA, biologic strategies that provide durable analgesia with reduced dosing frequency remain to be explored.
Objectives: To evaluate the efficacy, safety, and immunogenicity of two lead NGF-targeting Fc-fusion proteins for pain relief in dogs with naturally-occurring OA, compared with Librela™. Animals: Fifteen aged laboratory Beagle dogs with radiographically confirmed osteoarthritis OA and clinical evidence of OA pain. Materials and methods: In a randomized, parallel-group study, dogs received AKS-548d (90 µg), AKS-734 (90 µg), or Librela™ (0.5 mg/kg; n = 5/group). Pain and function were assessed using a modified Canine Brief Pain Inventory (mCBPI) at baseline and after treatment. Orthopedic examinations, body weight, clinical pathology, and immunogenicity assessments were performed at predefined intervals. General health and injection site observations were conducted throughout the study.
Results: All treatment groups showed reductions in pain and improvements in function from baseline. Most dogs achieved clinically meaningful improvement thresholds (≥ 1-point reduction in pain and ≥ 2-point reduction in function scores), with no statistically significant differences between groups. Safety profiles were acceptable, with no treatment-related hematologic or serum chemistry trends.
Conclusions: NGF-targeting Fc-fusion proteins provided clinically meaningful pain relief comparable to Librela™ and induced sustained NGF-neutralizing antibody responses. In parallel laboratory dog studies, neutralizing titers persisted for > 3 months after the final dose, supporting a long-acting immunotherapeutic approach with the goal of reducing injection frequency to approximately twice yearly for canine OA management.
