ATCvet code: QN02BG92
Pharmacodynamics
Mechanism of action:
Relfovetmab is a felinised monoclonal antibody (mAb) targeting nerve growth factor (NGF). NGF has been found to be elevated in the osteoarthritic joints of cats. Following a noxious stimulus, inflammatory cytokines and NGF are released by tissues of the joint. NGF binds to TrkA receptors located on immune cells to elicit the release of additional proinflammatory mediators, including NGF itself.
These inflammatory mediators lead to further peripheral sensitisation involved in pain perception. The inhibition of NGF mediated cell signalling reduces neurite outgrowth, neurogenic inflammation, inflammatory degradation mediators such as matrix metalloproteinases and has demonstrated to provide relief from pain associated with osteoarthritis (OA).
Clinical trials:
In a randomised, double masked, multi-centre clinical trial, the efficacy of relfovetmab was evaluated in cats with naturally occurring OA that were treated every three months at the approved label dose (0.5 - 1.25 mg/kg). Relfovetmab significantly reduced pain as assessed by cat owners using Client-Specific Outcome Measures (CSOM), by veterinarians using a categorical pain assessment and improved subjective scores of quality of life, temperament and happiness of the cats.
A total of 153 animals were enrolled in the relfovetmab treatment group and 154
animals were included in the placebo group. Treatment success, defined as a
reduction of ≥ 2 in the total CSOM score and no increase in any individual score, was achieved in 73.0%, 79.5% and 81.6% of the relfovetmab-treated cats and in 46.8%, 41.5% and 42.2% of placebo-treated cats assessed three months after one, two and three treatments, respectively. Statistically significant difference (p < 0.05) compared to placebo-treatment was demonstrated after all three treatments. Relfovetmab was demonstrated to provide analgesic effect within 3 days in a clinical trial in cats with naturally occurring OA.
Pharmacokinetics
In laboratory cats with naturally occurring OA, when relfovetmab was administered at the approved label dose (0.5 – 1.25 mg/kg), maximum serum drug concentration (Cmax) following subcutaneous administration was 2.95 mcg/ml and occurred on
average 3.6 days post-dosing. Bioavailability by the subcutaneous route was 41.8% and the elimination half-life was 5.4 days.
In a 6-month single dose clinical trial for safety and efficacy of relfovetmab in cats with OA, the elimination half-life was approximately 9 days. However, due to the infrequent sampling during this study, this calculated half-life may not be as accurate as that determined in the laboratory study (5.4 days). In a 9-month repeat dose clinical trial for safety and efficacy of relfovetmab in cats with OA, no accumulation was observed with repeat dosing.
Relfovetmab, like endogenous proteins, is expected to be degraded into small peptides and amino acids via normal catabolic pathways. Relfovetmab is not metabolised by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely.
Immunogenicity:
In a 9-month repeat dose clinical trial for safety and efficacy at the approved label dose (0.5 - 1.25 mg/kg) in adult cats with OA, immunogenicity was infrequently observed (2% of treated cats). Immunogenicity may have no effect or may result in a decrease in efficacy. There were no adverse events related to the immunogenicity findings.