Data to be presented at the ‘virtual annual meeting’ of the American Society for Colposcopy and Cervical Pathology (ASCCP) to be held April 1 and 2, 2020, demonstrates that VGX-3100 (Inovio Pharmaceuticals) is effective in women with vulvar dysplasia*, also known as vulvar intraepithelial neoplasia (VIN) orvulvar high grade squamous intraepithelial lesion (HSIL), a precancerous condition noted for abnormal changes in the skin of the vulva caused by high-risk human papillomavirus (HPV) types 16 and/or 18.

The open-label Phase II study, designed to evaluate the safety and efficacy of VGX-3100, enrolled 33 adult women 18 and older, with precancerous vulvar dysplasia caused by HPV-16 and/or HPV-18. The key efficacy measures being evaluated are the resolution of HSIL, non-detectability of HPV 16/18, and the decrease in the lesion area.

A total of 22 of these trial participants received all 4 doses of the investigational drug and will be evaluated to the end of the study. Earlier this month, researchers conducting the trial reported interim data on the 10 subjects who have completed their primary endpoint evaluation at six months following treatment with VGX-3100. Based upon the available results, 80% (8 out of 10 subjects) had a reduction (2 cm2 on average) in qualifying lesion area (average 60% reduction) of which 20% (2 of 10) completely resolved their vulvar HSIL and had no virus detectable in the healed area, 6 months following treatment.

A total of 33 women received 4 doses of VGX-3100 at weeks 0, 4, 12, and 24, of whom 8 subjects also received topical imiquimod, which was being evaluated as an adjunctive treatment.

Enrollment into the imiquimod arm was halted due to having no meaningful improvement upon the efficacy of VGX-3100 alone. Efficacy at 6 months following VGX-3100 treatment will be reported for all participants with available data, 22 of whom received VGX-3100 alone. Three participants have discontinued due to reasons of moving (1 subject) and electing for earlier surgery (2 subjects). The trial will follow treated participants for up to 1 year after the 4th dose.

Safety results were consistent with the known safety profile of VGX-3100. There were no drug-related serious adverse events. No cases of carcinoma have been observed.

Orphan disease
Vulvar high-grade squamous intraepithelial lesion (HSIL) is an orphan condition that usually requires surgery, which has significant physical and psychosocial impacts (e.g. severe pain, disfigurement, sexual dysfunction). However, the success of such surgery is marginal, as the recurrence rate of high-grade vulvar pre-cancer is approximately 30% to 50% three years post-treatment. Furthermore, less than 5% of women with vulvar HSIL exhibit spontaneous resolution. Without adequate treatment, vulvar HSIL can progress to vulvar cancer which is, according to data from the American Cancer Society, projected to claim approximately 1,350 lives in the U.S. in 2020 alone.

If left untreated vulvar pre-cancers can progress to invasive cancer of the vulva. Approximately 27,000 cases of HPV-related vulvar pre-cancers occur in the U.S. each year with a similar number of estimated cases in Europe each year. HPV-16 and/or HPV-18 are involved in about 80% of HPV-related vulvar pre-cancers cases in the U.S. and Europe. Once vulvar pre-cancers develop, spontaneous regression (i.e. a natural resolution of the lesion) is rare and occurs in 1.5% to 5% of cases. An estimated 6,000 new cases of vulvar cancer occur in the U.S. each year with about 50% to 80% of those being HPV-associated.

[We’re] developing VGX-3100 as a comprehensive treatment for HPV precancerous diseases. These proof-of-concept data take us one step closer to a better approach to treat vulvar precancer and improve women’s health,” noted Prakash Bhuyan, MD Ph.D., Vice President and Head of Clinical Development of HPV Therapeutics for Inovio Pharmaceuticals.

“This novel platform allows effective immune stimulations in the face of long-standing viral-induced precancer for this highly morbid disease. Many of these patients face years of sequential surgical resections and markedly impaired sexual function, apprehension about cancer risk, and some cases invasive cancer requiring highly morbid therapy,” explained Robert Edwards, MD, Milton Lawrence McCall Professor and Chair, Department of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh and Principal Coordinating Investigator for the trial.

* The vulva describes a women’s outside genital structures and includes the area outside of the opening of the vagina.

Clinical trials
Evaluation of VGX-3100 and Electroporation Alone or in Combination With Imiquimod for the Treatment of HPV-16 and/or HPV-18 Related Vulvar HSIL (Also Referred as VIN 2 or VIN 3) – NCT03180684

Reference
[1] Preliminary Results of an Open-Label Phase 2 Study of VGX-3100 for the Treatment of HPV-16 and/or HPV-18 (HPV-16/18) Related Vulvar HSIL.