Vulvar Dysplasia and Carcinoma

April 28, 2008

Graceway Pharmaceuticals released positive results from a phase III trial of Aldara for the treatment of Vulvar intraepithelial neoplasia (VIN). This randomized study enrolled fifty-two subjects with grade 2 or 3 VIN lesions. The subjects received Aldara Cream (5%) or placebo cream applied to lesions twice a week for sixteen weeks. The primary endpoint was a reduction in lesion size of more than 25% four weeks after the end of treatment (twenty weeks after the beginning of treatment). This endpoint was reached by 81% of subjects treated with Aldara and in none of the subjects treated with placebo (P less than .001). Lesions were completely cleared in 34% of the Aldara group and an additional 19% of the subjects experienced a reduction in lesion size greater than 75%. All nine subjects who were completely clear at twenty weeks remained clear at twelve months. Four of these nine subjects had two or three surgeries for VIN before being treated with Aldara. Secondary endpoints included histologic regression from grade 2 or 3 VIN to a lower grade, clearance of human papillomavirus (HPV) and relief of clinical symptoms at twenty weeks and twelve months. Histologic regression from grade 2 or 3 to a lower grade occurred in 69% of subjects treated with Aldara and 4% of those treated with placebo (P less than .001). Complete histologic clearance was reported in eight Aldara-treated patients. Histologic regression was strongly associated with viral clearance (P less than .001). At twenty weeks, HPV was completely cleared in seventeen lesions; fifteen after treatment with Aldara and two after treatment with placebo. A significant reduction in itching and pain was reported in the Aldara-treated arm versus those treated with placebo at twenty weeks (P=.008 and P=.004, respectively) and at twelve months (P=.04 and P=.02, respectively). There was no significant difference between treatment groups on self-reported, health-related quality of life, body image, or sexuality at either time point. Based on the results Graceway plans to continue with the development of Aldara for this indication.