Mechanism of action
Bedinvetmab is a canine monoclonal antibody (mAb) targeting Nerve Growth Factor (NGF). The inhibition of NGF mediated cell signalling has demonstrated to provide relief from pain associated with osteoarthritis.
In a 6-month laboratory study of healthy, adult Beagles administered bedinvetmab every 28 days at doses ranging from 1-10 mg/kg, AUC and Cmax increased nearly in proportion to dose and steady-state was achieved after approximately 2 doses. In a laboratory pharmacokinetic study at the clinical label dose (0.5-1.0 mg/kg bw), peak serum drug levels (Cmax) of 6.10 μg/ml were observed at 2-7 days (tmax = 5.6 days) after subcutaneous dosing, the bioavailability was approximately 84%, the elimination half-life was approximately 12 days, and the mean AUC0-∞ was 141 μg x d/ml.
In a field effectiveness study at the label dose in dogs with osteoarthritis, the terminal half-life averaged 16 days. Steady state was achieved after 2 doses.
Bedinvetmab, like endogenous proteins, is expected to be degraded into small peptides and amino acids via normal catabolic pathways. Bedinvetmab is not metabolised by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely.
The presence of binding antibodies to bedinvetmab in dogs was assessed using a multitier approach. In field studies of dogs with osteoarthritis receiving bedinvetmab once monthly, the appearance of anti-bedinvetmab antibodies was infrequent. None of the dogs exhibited any adverse clinical signs considered to be associated with binding antibodies to bedinvetmab.
In field studies lasting up to 3 months, treatment of dogs with osteoarthritis was demonstrated to have a favourable effect on the reduction of pain assessed by the Canine Brief Pain Inventory (CBPI). CBPI is an assessment by the animal owner of an individual dog’s response to pain treatment as assessed by pain severity (scale of 0 to 10, where 0 = no pain and 10 = extreme pain), interference of pain with the dog’s typical activities (scale of 0 to 10, where 0 = no interference and 10 = completely interferes) and quality of life. In the pivotal EU multicentre field study, 43.5% of the Librela-treated dogs and 16.9% of the placebo-treated dogs demonstrated treatment success, defined as a reduction of ≥1 in pain severity score (PSS) and ≥2 in pain interference score (PIS), on day 28 after the first dose. An onset of efficacy was demonstrated at 7 days post administration, with treatment success demonstrated in 17.8% of the Librela-treated dogs and 3.8% of the placebo-treated dogs. Treatment with bedinvetmab has demonstrated a positive effect on all three components of the CBPI. Data from an uncontrolled follow-up study lasting up to 9 months indicated sustained efficacy of treatment.
Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements.