INOVIO VGX-3100 HPV Cancer Vaccine Description For 2022
INOVIO's VGX-3100 is an investigational immunotherapy vaccine that includes DNA plasmids targeting the E6 and E7 proteins of human papillomavirus (HPV) types 16 and 18. VGX-3100 is HPV-specific immunotherapy developed as a non-surgical treatment for high-grade cervical dysplasia and related underlying persistent HPV infection. VGX-3100 works in vivo to activate functional, antigen-specific CD-8 T-cells to clear persistent HPV 16/18 infection and cause regression of pre-cancerous cervical dysplasia.
The company announced on May 10, 2022, based on feedback from the U.S. Food and Drug Administration (FDA), INOVIO has changed its development plans for VGX-3100 for HPV-16/18-associated cervical HSIL to a biomarker-selected population. In a recent preliminary letter, the FDA advised INOVIO that the REVEAL2 Phase 3 study would not be sufficient to support approval of a potential marketing application for VGX-3100 in that population.
The FDA recommended that using REVEAL2 as an exploratory study to evaluate a biomarker-selected population and then conducting one or two additional well-controlled trials in the biomarker-positive population would be more likely to provide sufficient evidence to support approval of a marketing application. To better assess potential efficacy in a biomarker-selected population, the Company plans to amend the fully enrolled REVEAL2 trial to revise the primary analysis population from the all-comers population to the biomarker-positive population. Both the biomarker-positive population and the all-comers population will be analyzed.
INOVIO's Phase 3 program in cervical HSIL is assessing the efficacy of VGX-3100 to regress cervical HSIL, a direct precursor to cervical cancer, and to eliminate the HPV-16 and/or HPV-18 infection that causes these lesions. The REVEAL studies are prospective, randomized, double-blind, placebo-controlled trials evaluating adult women with HPV-16 and/or HPV-18 positive biopsy-proven cervical HSIL. REVEAL1 provided one-year post-endpoint safety data for a minimum of 198 participants randomized, while REVEAL2 will provide efficacy and one-month safety data for a minimum of 198 participants.
INOVIO’s first-of-their-kind DNA medicines are precisely designed DNA plasmids delivered through INOVIO’s unique smart device directly into the body’s cells to produce an immune response robust enough to potentially treat and prevent disease.
On December 9, 2020, Prakash Bhuyan, M.D., Ph.D., Senior Vice President and Head of HPV Therapeutic Clinical Development at INOVIO, said, "Anal dysplasia is a rare disease that is typically treated via surgical excision, electro-cautery, or laser therapy, with up to 50% of patients experiencing disease recurrence within one year of surgical treatment. We are encouraged by these positive results from our Phase 2 trial and look forward to continuing our work in Phase 3 trials to develop systemic DNA-based immunotherapy that leverages our DNA medicines platform to improve the current standard of care."
On January 6, 2021, Robert Edwards, M.D., Milton Lawrence McCall, Professor and Chair, Department of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh, and Principal Coordinating Investigator for the Phase 2 clinical trial, said, "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."
The HPV-301 is a prospective, randomized, double-blind, placebo-controlled Phase 3 study to determine the efficacy, safety, and tolerability of VGX-3100 administered by intramuscular (IM) injection followed by electroporation (EP) delivered with CELLECTRA™ 5PSP in adult women with histologically confirmed cervical high grade squamous intraepithelial lesion (HSIL) (cervical intraepithelial neoplasia grade 2 [CIN2] or grade 3 [CIN3]) associated with human papillomavirus (HPV) 16 and/or HPV-18, was last updated on January 7, 2021. The Estimated Study Completion Date is April 2021.
Inovio has 15 DNA medicine clinical programs currently in development focused on HPV-associated diseases, cancer, and infectious diseases. DNA medicines are medicines composed of optimized DNA plasmids, which are small circles of double-stranded DNA synthesized or reorganized by a computer sequencing technology designed to produce a specific immune response in the body.
Inovio's DNA medicines deliver optimized plasmids directly into cells intramuscularly or intradermally using Inovio's proprietary hand-held smart device called CELLECTRA®. CELLECTRA uses a brief electrical pulse to open small pores in the cell reversibly to allow the plasmids to enter. Once inside the cell, the plasmids begin replicating, strengthening the body's own natural response mechanisms.
Administration with the CELLECTRA device ensures that the DNA medicine is delivered directly into the body's cells, where it can go to work immediately mounting an immune response. Inovio's DNA medicines are not interfering with or changing in any way an individual's own DNA, which is the case with gene therapy or gene editing.
Inovio is an innovative biotechnology company focused on discovering, developing, and commercializing its synthetic nucleic technology targeted against cancers and infectious diseases.
VGX-3100 is designed to treat pre-cancers and cancers caused by human papillomavirus (HPV). HPV-16/18 causes more than 90% of all anal cancer, which is now considered one of 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 U.S., and 8,590 news cases (5,900 in women and 2,690 in men) will be diagnosed in 2020.
VGX-3100 is delivered intramuscularly, followed by electroporation with a CELLECTRA-5PSP delivery device.
VGX-3100 News For 2018 - 2022
May 10, 2022 - The company announced changes for VGX-3100 following input from the FDA on the need for additional trials for a marketing application for the treatment of HPV-associated cervical high-grade squamous intraepithelial lesions.
December 14, 2021 - INOVIO announced updates on the Phase 3 program for VGX-3100 for HPV-associated cervical high-grade squamous intraepithelial lesions, including a one-year follow-up of efficacy and safety data in participants from REVEAL1, completing enrollment in REVEAL2, and advancing its pre-treatment biomarker candidate for VGX-3100 to be further developed with QIAGEN. In addition, INOVIO's development partner within Greater China, ApolloBio Corp., dosed the first participant in a separate Phase 3 trial in China.
March 2, 2021 - INOVIO announced its phase 3 trial, REVEAL 1 met primary and secondary endpoints. INOVIO expects to present REVEAL 1 findings at a scientific meeting this year.
January 6, 2021 - INOVIO announced positive efficacy results for an open-label Phase 2 trial of VGX-3100 to treat HPV-16 and HPV-18-associated vulvar dysplasia. A 25% or more reduction in HPV-16/18-associated vulvar HSIL (high-grade squamous intraepithelial lesion) was observed for 63% of trial participants (12 of 19) treated with VGX-3100 at six months post-treatment. Three out of the 20 participants with histology data (15%) resolved their vulvar HSIL and had no HPV-16/18 virus detectable in the healed area. By comparison, the spontaneous resolution of vulvar HSIL caused by HPV-16/18 is estimated to be only 2%. The trial also showed VGX-3100 to be safe and well-tolerated. Based on these results, INOVIO is planning to pursue Phase 3 development. Prakash Bhuyan, M.D., Ph.D., Senior Vice President and Head of HPV Therapeutic Clinical Development at INOVIO, said, "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."
December 9, 2020 - INOVIO announced positive Phase 2 efficacy results demonstrating that DNA medicine VGX-3100, the company's lead immunotherapy asset, showed resolution of HPV-16/18-associated precancerous anal lesions (HSIL) in 50% (11 of 22) of subjects six months following the start of treatment. The open-label, single-arm trial also showed VGX-3100 to be safe and well-tolerated in treating men and women with HPV-16-/18-associated anal dysplasia. INOVIO plans to pursue a registrational Phase 3 clinical trial for HPV-16-/18-associated anal dysplasia and apply rare and orphan disease designation for this indication in 2021.
March 26, 2020 - Inovio announced 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 (HSIL), a precancerous condition caused by high-risk human papillomavirus (HPV) types 16/18.
July 8, 2019 - Inovio announced that it had completed enrollment in its Phase 2 trial with VGX-3100 in patients with precancerous lesions of the vulva or vulvar intraepithelial neoplasia (VIN). VGX-3100 is an immunotherapy that targets human papillomavirus (HPV) 16 and 18 and is being studied to treat HPV-related precancerous lesions and the HPV infection that causes these lesions.
June 26, 2019 - Inovio has announced the completion of the target enrollment of 198 participants for its pivotal Phase 3 REVEAL 1 registration trial of VGX-3100, a novel DNA-based immunotherapy being tested to treat cervical dysplasia caused by human papillomavirus (HPV).
March 20, 2018 - Inovio will immediately receive $23 million in upfront payment; an additional $20 million in future regulatory milestone payments, and double-digit tiered royalties on future sales. “With this license and collaboration agreement we are now on the path to introduce late-stage innovative new drugs to meet severely unmet medical needs within the Greater China region," said Dr. Weiping Yang, Chief Executive Officer of ApolloBio. "We are excited at the potential for VGX-3100 to address multiple indications within HPV-associated precancer, and we are very pleased to launch this strategic collaboration with Inovio, an innovative global biotechnology partner.”
VGX-3100 Clinical Trials
Clinical Trial NCT03185013: Phase 3 Clinical Trial REVEAL 1 Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL. REVEAL 1 is designed to provide one-year safety data for a minimum of 198 patients on VGX-3100—the last Update Posted: February 3, 2021.
Clinical Trial NCT03721978: Phase 3 Clinical Trial REVEAL 2 Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL. A confirmatory Phase 3 trial (REVEAL 2) is currently enrolling and is designed to provide one-month safety data for a minimum of 198 patients. Last Update Posted: December 4, 2020.
Clinical Trial NCT03180684: Phase 2 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
Clinical Trial NCT03499795: Phase 2 VGX-3100 Delivered Intramuscularly (IM) Followed by Electroporation (EP) for the Treatment of HPV-16 and/or HPV-18 Related Anal or Anal/Peri-Anal, High-Grade Squamous Intraepithelial Lesion (HSIL) in Individuals Seronegative for Human Immunodeficiency Virus (HIV)-1/2.