Effects of Topically Applied Betulinic Acid and NVX-207 on Melanocytic Tumors in 18 Horses

SIMPLE SUMMARY: Melanomas are skin tumors of the pigment-producing melanocytes. Equine melanomas are among the most frequently diagnosed tumors affecting grey horses. The melanocytic tumors progress to malignancy in more than two-thirds of cases. Previous laboratory experiments and studies with horses utilizing the naturally occurring betulinic acid (BA) and its derivative NVX-207 showed promising results with respect to the topical (epicutaneous) treatment of equine melanoma. Therefore, the aim of this feasibility study was to gain first insights into the effect and safety of BA and NVX-207 in eighteen horses with early-stage melanocytic tumors after a 13-week-long topical application. The topical treatment was convenient and safe. Compared to a placebo, the data suggest a positive treatment effect from topical application of BA and NVX-207 on equine melanomas toward the end of the treatment period. However, the time period studied was too short to conclusively prove this. Further advancement of the investigational medicinal products studied herein could lead to an effective, topical and marketable novel drug which helps to relieve suffering and, consequently, improve the welfare of equine skin cancer patients. ABSTRACT: The naturally occurring betulinic acid (BA) and its derivative NVX-207 induce apoptosis in equine melanoma cells in vitro. After topical application, high concentrations of the substances can be reached in healthy equine skin. With the aim to investigate the effect and safety of topically applied BA and NVX-207 in horses with melanocytic tumors, the longitudinal, prospective, randomized, double-blind, placebo-controlled study protocol included eighteen Lipizzaner mares with early-stage cutaneous melanoma assigned to three groups. Melanocytic lesions were topically treated either with a placebo, 1% BA or 1% NVX-207 twice a day for 91 days. Caliper measurements, clinical examinations and blood tests were performed to assess the effects and safety of the medication. The topical treatment was convenient and safe. The volumes of tumors treated with BA were significantly reduced over time as compared to tumors treated with the placebo from day 80 of the study. Although treatment with NVX-207 seemed to decrease tumor volume, these results did not reach statistical significance. The findings must be regarded as preliminary due to the limited group size and need to be replicated in a larger cohort with modified pharmaceutical test formulations. Accordingly, the treatment protocol cannot yet be recommended in its current form.