Cathepsin K Inhibition by VBX1000 Alleviates Canine Periodontitis

Jerzy Pawel Gawor^1,2*Daria Ziemann²Isabelle Druet³Julien Salindre⁴Alicja Gajosz⁵Paweł Kowalczyk⁶Noémie Dam⁷Dominique Tierny⁸Matthieu Dubruque⁷Remy Hanf^7*

• ¹24-hour veterinary clinic Arka, Krakow, Poland
• ²Klinika Weterynaryjna Arka, Kraków, Poland
• ³Alliance, Bordeaux, France
• ⁴Clinique Veterinaire, Mirambeau, France
• ⁵Veterinary clinic, Warsaw, Poland
• ⁶Veterinary clinic, Lodz, Poland
• ⁷Vetbiolix, Loos, France
• ⁸OCRvet, Lille, France

The efficacy and safety of a novel Cathepsin K inhibitor, VBX1000, were evaluated in client-owned dogs suffering from periodontal disease. This open-label study recruited twenty dogs (n=20) with at least 3 teeth at stage 2 or 3 of periodontal disease. Dogs were orally treated once-a-day with VBX1000 (25 mg/kg or 50 mg/kg, n=10 per group) for 60 days, and then with 50 mg/kg once-a-day for an additional 30 days. The first objective was to assess evolution compared to pre-treatment of plasma carboxy-terminal telopeptide of collagen type 1 (CTX1) used as a marker of target engagement and bone resorption. In each evaluated tooth (n=60; three teeth per dog), evolution counter to baseline of clinical attachment loss (CAL), periodontal probing depth (PPD), and bleeding on probing index (BPI) were evaluated The effects of Cathepsin K inhibitor on alveolar bone defects were assessed with intraoral dental radiography (DR) performed at inclusion and at the end of the treatment period. A confirmatory analysis was performed in a subpopulation (n=10 dogs; 30 teeth) using the cone beam computed tomography scan (CBCT) imaging technique. Throughout the treatment period, VBX1000 was well tolerated. At Day60, plasma CTX1 was significantly and similarly reduced compared with baseline (p<0.05) in the two groups. At the end of the treatment period (at Day90) in the total population (n=20), plasma CTX1 was 0.10±0.04 ng/mL relative to 0.26±0.20 ng/mL at baseline (p<0.001). DR before and after treatment showed decreases in width (n=60 teeth; three teeth/dog; p<0.0001), depth (p<0.05), and height of bone defects measured between the root and the maxillary bone. These effects on bone defects were confirmed in a subpopulation analyzed by CBCT. At the end of the treatment period, clinical attachment loss (CAL) was reduced relative to pretreatment: 2.87±1.73 mm compared to 3.86±2.06 mm (n=60; p<0.0001). Likewise, the periodontal probing depth (PPD) was reduced 2.71±1.03 mm compared to 3.69±1.23 mm (n=60, p<0.0001). Conclusion: The findings support the inhibition of cathepsin K by VBX1000 as a new therapeutic approach for mild-to-moderate periodontal disease in dogs. A randomized, double blinded placebo-controlled trial in dogs should confirm the potential of VBX1000 in this indication.