26 March 2020 - - US-based Inovio Pharmaceuticals, Inc. (NASDAQ: INO) has released positive interim results from an open-label, Phase 2 study showing its lead DNA medicine candidate VGX-3100 to be safe and effective in treating men and women with anal dysplasia, also known as high grade squamous intraepithelial lesion, a precancerous condition caused by high-risk human papillomavirus types 16/18, the company said.

Of the 20 subjects who had results at the time of data review, 50% (10 of 20 subjects) showed clearance of HPV-16/18 associated precancerous lesions and 75% (15 of 20 subjects) demonstrated an overall decrease in the number of lesions six months after the start of treatment.

No cases of anal cancer have been observed in the trial.

The results support the ability of VGX-3100 to effectively treat multiple HPV associated diseases and will be presented in the virtual session of the annual American Society for Colposcopy and Cervical Pathology (ASCCP) meeting titled: Preliminary Results of an Open-label Phase 2 Study of VGX-3100 for the Treatment of HPV16 and/or HPV-18 (HPV16/18) related Anal HSIL.

Anal dysplasia or anal HSIL, is an orphan disease that affects men and women in both immunocompetent and immunocompromised populations.

Fewer than 1 in 5 people with HPV 16/18-associated precancerous dysplasia exhibit spontaneous resolution at one year.

Without adequate treatment anal HSIL could progress to anal cancer.

HPV 16/18 cause more than 90% of all anal cancer, which is now considered one the most rapidly rising causes of cancer incidence and mortality.

According to the American Cancer Society, anal cancer will claim the lives of more than 1,300 people in the US and 8,590 news cases (5,900 in women and 2,690 in men) will be diagnosed in 2020 and according to a study published November 2019 in the Journal of the National Cancer Institute, from 2001 to 2015 the overall incidence of anal cancer increased by 2.7% per year and mortality jumped by 3.1% each year

Currently, the treatments for anal dysplasia are surgical excision, electro-cautery or laser therapy.

Up to 50% of those treated with these invasive options experience disease recurrence within one year of treatment and nearly 70% experience recurrence within three years. Therefore, many patients with this condition need multiple invasive treatments.

VGX-3100 Safety and Efficacy Highlights for Anal Dysplasia

The first 20 subjects on VGX-3100 demonstrated safety results consistent with the known safety profile of VGX-3100. There were no drug-related serious adverse events.

75% showed an overall decrease in the number of lesions 6 months after treatment and 50% of subjects showed no HPV-16/18 associated precancerous lesions

Results further support proof of concept for DNA medicines as also demonstrated in prior VGX-3100 Phase 2b study in high-risk HPV-associated precancerous cervical dysplasia 

This open-label, multi-center Phase 2 study is designed to evaluate the safety and efficacy of VGX-3100 in adults with precancerous anal dysplasia caused by HPV-16 and/or HPV-18.

Twenty three subjects who are human immunodeficiency virus negative with histologically confirmed anal or anal/peri-anal high-grade squamous intraepithelial lesion associated with human papilloma virus -16 and/or HPV-18 enrolled.

One subject discontinued due to an unrelated adverse event. Twenty two received three doses of VGX-3100 administered by Inovio's Cellectra 5PSP smart device at Day 0, Week 4 and Week 12.

Participants are scheduled to be followed to Week 88.

This study builds on significant clinical benefits demonstrated with Inovio's HPV-associated DNA medicines in multiple clinical trials.

Specifically, VGX-3100 in a Phase 2 proof-of-concept trial for cervical dysplasia demonstrated a complete response in 43 out of 107 patients in regression of high-grade cervical lesions and elimination of the underlying HPV infection.

Additionally, two out of four metastatic HPV-associated head and neck cancer patients treated with MEDI0457 and a PD-1 check point inhibitors in a Phase 1 study experienced a long-term complete response for more two years and counting.

Lastly, a pilot study of Inovio's DNA medicine INO-3107 in recurrent respiratory papillomatosis resulted in two out of two patients delaying surgery due to lack of tumor recurrence.

VGX-3100 is a DNA medicine 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 dysplasia.

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.

It 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 dysplasia (CIN2/3 or HSIL), treatment with VGX-3100 resulted in a statistically significantly greater regression of cervical dysplasia and clearance of HPV-16/18 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 has 15 DNA medicine clinical programmes currently in development focused on HPV-associated diseases, cancer, and infectious diseases, including coronaviruses MERS and COVID-19 under grants from the Coalition for Epidemic Preparedness Innovations.