Article of the Week

 

We will be posting commentaries on articles relating to internal medicine and endocrinology that we think are of interest.

 

January 13th, 2022

 

Frunevetmab, a felinized anti-nerve growth factor monoclonal antibody, for the treatment of pain from osteoarthritis in cats

 

Nerve growth factor (NGF) has an important role in nociceptor sensitization in a wide variety of both acute and chronic pain states including OA pain. NGF appears to play a particularly important role in OA pain. There is strong evidence of robust analgesic effects of monoclonal antibodies (mAbs) directed against NGF. These mAbs, directed against NGF, bind NGF therefore sequestering it and preventing it from interacting with its receptors.

 

Anti-NGF mAbs are effective in dogs with OA, with the first canine anti-NGF mAb (bedinvetmab) recently approved for use in EU. In human studies performed thus far, dose-dependent efficacy was demonstrated in patients with moderate to severe pain associated with symptomatic knee or hip OA.  Efficacy appeared greater than that observed with NSAIDs or opiates. In cats, proof-of-concept and pilot field studies demonstrated efficacy of a felinized anti-NGF mAb (frunevetmab) in the treatment of DJD-associated pain.

 

Despite considerable advances over the last 15 years in our understanding of how to measure chronic pain in cats, a profound placebo effect (up to 80%) is described in clinical chronic pain trials using subjective owner assessment that trends higher with longer duration studies.

 

The objective of this study was to evaluate the efficacy of 3 SC administered doses of frunevetmab (recently approved as Solensia in the European Union) given at monthly intervals in a randomized, placebo-controlled, parallel-group, double-blind superiority study across multiple veterinary practices. This study was conducted for registration purposes.

 

Background: Frunevetmab, a felinized antinerve growth factor monoclonal antibody, effectively decreases osteoarthritis (OA) pain in cats.

 

Objective: To evaluate the efficacy of frunevetmab given at monthly intervals in a randomized, placebo-controlled, parallel-group, double-blind superiority study.

 

Animals: Two hundred seventy-five client-owned cats with naturally-occurring OA pain and associated mobility impairment and disability.

 

Methods: Randomized, placebo-controlled, parallel-group, double-blind, superiority study. Following screening, cats received frunevetmab (nominal dose of 1.0 mg/kg, SC [effective dose range of 1.0-2.8 mg/kg]) or placebo on days 0, 28, and 56. Outcome measures were owner questionnaires and veterinary physical and orthopedic evaluations at days 28, 56, and 84. Success/failure rates (and numbers needed treat, NNT) and change in scores (and standardized effect size, ES) were analyzed.

 

Results: Frunevetmab (182) and placebo (93) treated cats were enrolled and received at least 1 treatment. Significant improvement with frunevetmab over placebo occurred at days 28 and 56 for the client specific outcome measures (CSOM) questionnaire (success rates and total scores [NNT of 9 and ES of 0.3 at day 56]); at days 28 and 56 for owner-assessed global treatment response; and at days 56 and 84 for veterinarian-assessed joint pain (ES of 0.18 at day 56). Adverse events did not differ between groups, except skin disorders which collectively occurred significantly more frequently in frunevetmab treated (32/182 cats) vs placebo (8/93 cats).

 

Conclusions and Clinical Importance: Frunevetmab has the potential to address a critical gap in the treatment of pain because of osteoarthritis in cats.