PLYMOUTH MEETING, Pa., Jan. 6, 2021 /PRNewswire/ -- INOVIO (NASDAQ:INO), a biotechnology company focused on bringing to market precisely designed DNA medicines to treat and protect people from infectious diseases, cancer and HPV-associated diseases, today 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 upon these results INOVIO is planning to pursue Phase 3 development.
Dr. Robert Edwards, MD, 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."
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."
VGX-3100 Phase 2 Vulvar Dysplasia Trial Highlights
- Trial participants were 24 women between 22 and 70 years of age at entry and other than having HSIL were healthy.
- 80% (20/25) had VIN3 disease (the more severe form of VIN) and 88% (22/25) had a history of 1 or more recurrences
- There were no discontinuations due to adverse events; five participants elected to withdraw for reasons unrelated to adverse events.
- 19 participants had digital photography data, and 12 (63%) had clinically significant lesion reduction as defined by a reduction of lesion area of more than 25%.
- 20 participants had histology and virology data and 3 (15%) resolved their vulvar HSIL and had no HPV-16/18 virus detectable in the healed area.
- Histology was assessed by up to two independent pathologists and non-detectability of HPV-16/18 from lesion tissue using PCR (polymerase chain reaction)-based testing, at six months following the administration of VGX-3100.
- Efficacy endpoints were measured six months post-treatment.
- Safety will continue to be assessed for 18 months following the last dose.
- The most observed adverse event was injection site pain, the majority of which were mild-to-moderate.
- No cases of vulvar cancer have been observed in the trial.
For more information about the Phase 2 clinical trial, please visit www.clinicaltrials.gov (search identifier NCT03180684).
About Vulvar Dysplasia
Vulvar dysplasia is a rare disease that affects women in immunocompetent and immunocompromised populations. Fewer than 2% of women with HPV-16/18-associated precancerous vulvar dysplasia exhibit spontaneous resolution. HPV-16/18-associated precancerous vulvar lesions (vulvar HSIL) are known to be difficult to treat, and typically require repeat ablation and excision procedures to achieve disease and risk reduction. Without adequate treatment vulvar HSIL can progress to vulvar cancer. In 2017, vulvar cancer was diagnosed in 1354 women in the U.S. and 411 died from vaginal cancer.1
VGX-3100 is a DNA medicine in clinical trials for the treatment of three HPV-16/18 related disease states – anal dysplasia, vulvar dysplasia and cervical dysplasia. The cervical dysplasia program is in late Phase 3 clinical trials (REVEAL1 and REVEAL2). VGX-3100 is designed to utilize the patient's own immune system to clear HPV-16/18-associated high-grade precancerous lesions with the aim of reducing the risk of cancer.
About INOVIO's HPV-Associated DNA Medicines Clinical Programs
This Phase 2 clinical trial builds on significant clinical benefits demonstrated with INOVIO's HPV-associated DNA medicines across multiple clinical trials. Specifically, VGX-3100 in a Phase 2 proof-of-concept trial for cervical dysplasia demonstrated a response in 43 out of 107 patients in regression of high-grade cervical lesions and elimination of the underlying HPV infection2. A Phase 2 trial of VGX-3100 in the treatment of anal HSIL was also conducted with positive efficacy results3. 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 trial experienced a long-term complete response for more two years and counting; 18 out of 22 head and neck patients treated with MEDI0457 have not progressed for over four years post-treatment. Lastly, a pilot study of INOVIO's DNA medicine INO-3107 in recurrent respiratory papillomatosis (RRP) resulted in two out of two patients delaying surgery due to lack of tumor recurrence.
About INOVIO's DNA Medicines Platform
INOVIO has 15 DNA medicine clinical programs currently in development focused on HPV-associated diseases, cancer, and infectious diseases, including coronaviruses associated with MERS and COVID-19 diseases being developed under grants from the Coalition for Epidemic Preparedness Innovations (CEPI) and the U.S. Department of Defense. DNA medicines are composed of optimized DNA plasmids, which are small circles of double-stranded DNA that are synthesized or reorganized by a computer sequencing technology and 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®. The CELLECTRA device uses a brief electrical pulse to reversibly open small pores in the cell to allow the plasmids to enter, overcoming a key limitation of other DNA and other nucleic acid approaches, such as mRNA. Once inside the cell, the DNA plasmids enable the cell to produce the targeted antigen. The antigen is processed naturally in the cell and triggers the desired T cell and antibody-mediated immune responses. Administration with the CELLECTRA device ensures that the DNA medicine is efficiently delivered directly into the body's cells, where it can go to work to drive an immune response. INOVIO's DNA medicines do not interfere with or change in any way an individual's own DNA. The advantages of INOVIO's DNA medicine platform are how fast DNA medicines can be designed and manufactured; the stability of the products, which do not require freezing in storage and transport; and the robust immune response, safety profile, and tolerability that have been observed in clinical trials.
With more than 2,000 patients receiving INOVIO investigational DNA medicines in more than 7,000 applications across a range of clinical trials, INOVIO has a strong track record of rapidly generating DNA medicine candidates with potential to meet urgent global health needs.
INOVIO is a biotechnology company focused on rapidly bringing to market precisely designed DNA medicines to treat and protect people from infectious diseases, cancer, and diseases associated with HPV. INOVIO is the first and only company to have clinically demonstrated that a DNA medicine can be delivered directly into cells in the body via a proprietary smart device to produce a robust and tolerable immune response. Specifically, INOVIO's lead candidate VGX-3100, currently in Phase 3 trials for precancerous cervical dysplasia, destroyed and cleared high-risk HPV 16 and 18 in a Phase 2b clinical trial. High-risk HPV is responsible for 70% of cervical cancer, 91% of anal cancer, and 69% of vulvar cancer. Also in development are programs targeting HPV-related cancers and a rare HPV-related disease, recurrent respiratory papillomatosis (RRP); non-HPV-related cancers glioblastoma multiforme (GBM) and prostate cancer; as well as externally funded infectious disease DNA vaccine development programs in Zika, Lassa fever, Ebola, HIV, and coronaviruses associated with MERS and COVID-19 diseases. Partners and collaborators include Advaccine, ApolloBio Corporation, AstraZeneca, The Bill & Melinda Gates Foundation, Coalition for Epidemic Preparedness Innovations (CEPI), Defense Advanced Research Projects Agency (DARPA)/Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND)/Department of Defense (DoD), HIV Vaccines Trial Network, International Vaccine Institute (IVI), Kaneka Eurogentec, Medical CBRN Defense Consortium (MCDC), National Cancer Institute, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Ology Bioservices, the Parker Institute for Cancer Immunotherapy, Plumbline Life Sciences, Regeneron, Richter-Helm BioLogics, Thermo Fisher Scientific, University of Pennsylvania, Walter Reed Army Institute of Research, and The Wistar Institute. INOVIO also is a proud recipient of 2020 Women on Boards "W" designation recognizing companies with more than 20% women on their board of directors. For more information, visit www.inovio.com.
This press release contains certain forward-looking statements relating to our business, including our plans to develop and manufacture DNA medicines, our expectations regarding our research and development programs, and our ability to successfully manufacture and produce large quantities of our product candidates if they receive regulatory approval. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in preclinical studies, clinical trials, product development programs and commercialization activities and outcomes, our ability to secure sufficient manufacturing capacity to mass produce our product candidates, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA medicines, our ability to support our pipeline of DNA medicine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by us or our collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that we and our collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide us with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether we can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of our technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2019, our Quarterly Report on Form 10-Q for the quarter ended September 30, 2020 and other filings we make from time to time with the Securities and Exchange Commission. There can be no assurance that any product candidate in our pipeline will be successfully developed, manufactured or commercialized, that final results of clinical trials will be supportive of regulatory approvals required to market products, or that any of the forward-looking information provided herein will be proven accurate. Forward-looking statements speak only as of the date of this release, and we undertake no obligation to update or revise these statements, except as may be required by law.
1 https://www.cdc.gov/cancer/vagvulv/statistics/#Ref2 accessed on 04JAN2021
2 Trimble et al., Lancet, 386, 10008, P2078-2088, 2015; https://doi.org/10.1016/S0140-6736(15)00239-1
3 Presented at ASCCP 2020 Scientific Meeting
SOURCE INOVIO Pharmaceuticals, Inc.