Inovio Pharmaceuticals, Inc. announced that it has commenced a phase 2 clinical trial to evaluate the efficacy of VGX-3100 in adult men and women with human papilloma virus (HPV)-related anal dysplasia. Recruitment is ongoing for patients who are HIV-negative with histologically confirmed anal or perianal high-grade squamous intraepithelial lesions (HSIL) associated with HPV-16 and/or HPV-18. The study is planning to enroll approximately 24 patients and will administer at least three doses of VGX-3100.

Anal HSIL or dysplasia is the precursor to anal cancer, which is estimated to cause more than 1,100 deaths in the United States in 2018. Currently, the only treatments for anal dysplasia consist of surgical excision, electro-cautery or laser therapy, but more than 50% of those treated with these current treatments experience recurrence of the disease.

Dr. Céline Bouchard, FRCSC, gynecologist, colposcopist and Coordinating Principal Investigator, said, “The large burden of disease rests in the general population. As more than 70% of anal cancers in the United States occur among HIV-negative men and women, a non-surgical immunotherapy to eradicate precancerous perianal and/or anal lesions caused by HPV types 16 or 18 infection would represent a major breakthrough for the treatment of this disease and the prevention of anal cancer.”

Dr. J. Joseph Kim, Inovio's president and CEO, said, “Inovio is boldly targeting the world’s No. 1 sexually transmitted disease the HPV virus across the continuum of conditions with our treatment that has demonstrated efficacy eliminating disease and clearing the underlying HPV infection. This compact Phase 2 efficacy trial represents an important step towards Inovio’s aim to develop a comprehensive immunotherapeutic solution to HPV-related diseases, especially given that anal dysplasia remains an underdiagnosed condition which needs better treatment options. Inovio is rapidly moving on a path to become the ‘go-to’ immunotherapeutic solution provider for all diseases caused by HPV, including cervical, vulvar and anal precancers and with our partner MedImmune/AstraZeneca for HPV-related cancers.”

This open-label, multi-center Phase 2 study is designed to evaluate the safety and efficacy of VGX-3100 administered by intramuscular (IM) injection w Cellectra delivery system in adult men and women who are human immunodeficiency virus (HIV) negative with HSIL associated with HPV-16 and/or HPV-18. Prior study results utilising Inovio’s VGX-3100 immunotherapy, which is also in a Phase 3 trial evaluating treatment for cervical dysplasia, supported expanding treatment indications for patients associated with HPV-16 and/or HPV-18. In a Phase 2 trial for cervical dysplasia, VGX-3100 demonstrated a systemic response (vs. localised surgery) and clearance of cervical lesions and eliminating the underlying HPV infection in many patients.

VGX-3100 is a DNA-based immunotherapy under phase 3 investigation for the treatment of HPV-16 and HPV-18 infection and precancerous lesions of the cervix. Inovio is in open-label phase 2 clinical trials evaluating its efficacy for treating HPV-related vulvar and anal precancers. VGX-3100 has the potential to be the first approved treatment for HPV infection of the cervix and the first non-surgical treatment for precancerous cervical lesions. VGX-3100 works by stimulating a specific immune response to HPV-16 and HPV-18, which targets the infection and causes destruction of precancerous cells. In a randomised, double-blind, placebo-controlled phase 2b study in 167 adult women with histologically documented HPV 16/18 cervical HSIL (CIN2/3), treatment with VGX-3100 resulted in a statistically significantly greater decrease in cervical HSIL and clearance of HPV infection vs. placebo. The most common side effect was injection site pain, and no serious adverse events were reported. VGX-3100 utilises the patient’s own immune system to clear HPV-16 and HPV-18 infection and precancerous lesions without the increased risks associated with surgery, such as loss of reproductive health and negative psychosocial impacts.

Inovio is advancing the medical potential of a unique class of immunotherapy technology. Its DNA-based platform, which is the foundation for all of Inovio’s products, including VGX-3100, is unique in its ability to leverage the body’s naturally existing mechanisms to generate robust, highly targeted immune responses to prevent and treat disease and to do so in the body without harmful side effects. Its SynCon immunotherapy design and Cellectra delivery transform novel genetic blueprints into functional antibody and killer T cell responses. Inovio was the first to report the activation in the body of significant, antigen-specific functional T cells correlated to statistically significant efficacy in a placebo-controlled, randomised, double-blind phase 2b clinical trial (HPV-related precancer), with a very favorable safety profile. These data were published in The Lancet and independently described as a “major breakthrough” in the field by US National Cancer Institute scientists. Inovio has achieved significant antigen-specific immune responses against multiple diseases and is advancing a growing pipeline of cancer and infectious disease immunotherapies and vaccines.