Novel HPV Vaccine Shows Reduced High-Grade Squamous Intraepithelial Lesions in Women

VGX-3100, a therapeutic DNA vaccine, achieved a 25% reduction or more reduction in HPV-16/18-associated vulvar high-grade squamous intraepithelial lesion (HSIL) in 63% of patients at 6 months after treatment with the agent, according to findings from an open-label phase 2 clinical trial (NCT03180684) announced in a press release from INOVIO Pharmaceuticals, Inc.

"These phase 2 efficacy results are a very promising non-surgical advance for a recalcitrant disease that normally requires repetitive ablation and excision procedures to achieve disease and risk reduction, and may offer a more safe, tolerable and efficacious treatment option for patients,” said Robert Edwards, MD, Milton Lawrence McCall Professor, and Chair, Department of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh, the principal investigator of the study, in a statement.

In addition to HPV-16/18 associated vulvar HSIL, treatment with VGX-3100 led to vulvar HSIL resolution in 3 out of 20 of patients who had histology data. Reportedly, HPV-16/18 virus was not detected at all in the treated area. On the other hand, there was only a 2% spontaneous resolution of vulvar HSIL. Vulvar cancer was not observed in any patients in the trial.

Adverse events were observed in the study, with the most common being injection site pain. Most cases of injection site pain were mild to moderate. There were no treatment discontinuations due to the emergence of AEs, but 5 patients did withdraw from the study. Patients enrolled in the study will continue to be followed for safety for 18 months following their last dose of VGX-3100.

"The reduction of precancerous disease offers a meaningful improvement in the management of this devastating disease and is a step forward towards the enhancement of women's healthcare, stated Prakash Bhuyan, MD, PhD, senior vice president and head of HPV Therapeutic Clinical Development, INOVIO Pharmaceuticals, Inc.

The phase 2 study of VGX-3100 included 24 female patients aged 22 to 70 years without comorbidities. Patient characteristics observed at study entry showed that 80% of the population had vulval intraepithelial neoplasia (VIN) 3 disease, and 88% showed a history of at least 1 recurrence.

Patients were eligible for enrollment given they were at least 18 years of age with HSIL of the vulva caused by HPV16/18 infection. The study excluded women differentiated VIN proven by biopsy, previous treatment for vulvar HSIL within 4 weeks prior to screening, were allergic to imiquimod 5% cream or an inactive ingredient in imiquimod 5% cream, were pregnant or breastfeeding, had immunosuppression due to an underlying illness, or had a significant acute or chronic illness.

VGX-3100 is currently under investigation in 2 phase 3 clinical trials (REVEAL1, NCT03185013

and REVEAL2, NCT03721978) for the prevention of HPV-16/18-associated high-grade precancerous lesions. The goal of both studies is to reduce the risk of patients developing cancer.

_Reference:

_{INOVIO's VGX-3100 demonstrates positive phase 2 efficacy in treatment of precancerous vulvar dysplasia caused by HPV-16/18. News release. INOVIO Pharmaceuticals, Inc. January 6, 2020. Accessed January 6, 2020. https://bit.ly/2XiyEcG}