Significant antigen-specific T-cell and antibody responses shown in low and medium dose groups
BLUE BELL, Pa.--(BUSINESS WIRE)-- Inovio Biomedical Corporation (NYSE Amex: INO), a leader in DNA vaccine design, development and delivery, announced today that the company has completed enrollment of all subjects for its therapeutic cervical cancer vaccine (VGX-3100) phase I trial. VGX-3100 is a DNA vaccine targeting the E6 and E7 proteins of human papillomavirus (HPV) types 16 and 18, and is delivered via in vivo electroporation.
This dose escalation study was designed to test the safety and immunogenicity of VGX-3100 in women with a previous history of cervical intraepithelial neoplasia (CIN) 2/3, a precursor lesion prior to the development of cancer. The trial enrolled patients in three cohorts of six subjects each with DNA vaccine doses at 0.6 mg (0.3 mg for each of two DNA plasmids), 2.0 mg, and 6.0 mg. The immunization regimen consists of each subject receiving the respective dose at day 0, month 1 and month 3. The vaccine is delivered using Inovio’s proprietary CELLECTRA® intramuscular electroporation delivery device.
All twelve patients from the first two dose cohorts have been evaluated for safety and immune responses. The vaccine has been well tolerated with an acceptable safety profile in all subjects tested. In general, reported adverse events and injection site reactions were mild to moderate and required no treatment.
The interim immunological analysis of blood samples collected before and after vaccination indicated the induction of antigen-specific immune responses against the target proteins produced by the vaccine. Antigen-specific cytotoxic T-lymphocyte (CTL) responses were observed against all four antigens (E6 and E7 proteins for HPV types 16 and 18).
In the first two cohorts, 6 of 12 vaccinated subjects (50%) developed significant CTL responses, with average CTL responses increasing in a dose-related fashion. Generation of tumor-specific T-cell responses is believed to be an important characteristic of a cancer therapeutic vaccine.
Inovio also tested the samples for antibody responses against the target antigens and observed strong antibody responses in 10 of 12 subjects (83%). Antibodies were generated against all four antigens, as tested by the enzyme-linked immunosorbent assay (ELISA). Moreover, the level of antibody responses in the second, mid-dose cohort was on average 5 - 10 fold higher than that observed in the lowest-dose cohort. The high antibody titers achieved in this study have not previously been observed in human clinical trials of other DNA immunogens.
Specific antibody responses to tumor antigens can function as an important surrogate potency marker for determining the immunogenicity of a vaccine, i.e. the ability of a vaccine to induce an immune response. Furthermore, Inovio believes these results further validate the usefulness of its DNA vaccine platform against infectious disease targets, where generation of antibodies has been shown to be protective.
“We are pleased to report the completion of enrollment for the VGX-3100 study. We have been working diligently to progress this program forward. The interim analyses of the vaccinated subjects from the first two cohorts indicate that our vaccine is highly immunogenic, generating antigen-specific T-cell and antibody responses that are amongst the highest reported from any previous human studies of DNA vaccines,” stated Dr. J. Joseph Kim, President and CEO.
“While VGX-3100 is a potentially important product against cervical cancer, we believe a successful completion of this study will mark an important event for our field as a whole and a strong valuation enhancing event for our company,” Dr. Kim added.
Inovio expects complete immunogenicity and safety data to be reported in early Q1 2011.
About HPV, Cervical Cancer and Inovio’s Therapeutic DNA Vaccine
Human papillomavirus (HPV) is the causative agent responsible for most cases of cervical cancer. HPV types 16 and 18 are responsible for about 70% of cervical cancer incidences. Globally, over 253,500 women die of cervical cancer each year.
Preventive vaccines such as GARDASIL® and CERVARIX® are playing a role in limiting infection of HPV. However, the huge number of patients already infected with HPV cannot be addressed by preventive vaccines and there is no viable therapeutic vaccine or drug to fight HPV and cervical cancer.
Inovio’s VGX-3100 is designed to express the E6 and E7 genes common to HPV types 16 and 18 and which are present in both pre-cancerous and cancerous cells transformed by these HPV types. The goal is to stimulate the body’s immune system to mount a T-cell response strong enough to cause the rejection of these unwanted cells from the body.
About Inovio Biomedical Corporation
Inovio Biomedical is focused on the design, development, and delivery of a new generation of vaccines, called DNA vaccines, to prevent and treat cancers and infectious diseases. The company’s SynCon™ technology enables the design of “universal” vaccines capable of protecting against multiple – including newly emergent, unknown – strains of pathogens such as influenza. Inovio’s proprietary electroporation-based DNA vaccine delivery technology has been shown by initial human data to safely and significantly increase gene expression and immune responses. Inovio’s clinical programs include HPV/cervical cancer (therapeutic), avian flu, and HIV vaccines. Inovio is developing its universal and avian influenza vaccines in collaboration with scientists from the University of Pennsylvania, the National Microbiology Laboratory of the Public Health Agency of Canada, and the NIH’s Vaccine Research Center. Other partners and collaborators include Merck, Tripep, University of Southampton, National Cancer Institute, and HIV Vaccines Trial Network. More information is available at www.inovio.com.
This press release contains, in addition to historical information, forward-looking statements. Such statements are based on management’s current estimates and expectations and are subject to a number of uncertainties and risks that could cause actual results to differ materially from those described in the forward-looking statements. Inovio is providing this information as of the date of this press release, and expressly disclaims any duty to update information contained in this press release.
Forward-looking statements in this press release include, without limitation, express and implied statements relating to Inovio’s business, plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines and pre-clinical and clinical studies. Actual events or results may differ from the expectations set forth herein as a result of a number of risks, uncertainties and other factors, including but not limited to: Inovio has a history of losses; all of Inovio’s potential human products are in research and development phases; no revenues have been generated from the sale of any such products, nor are any such revenues expected for at least the next several years; Inovio’s product candidates will require significant additional research and development efforts, including extensive preclinical and clinical testing; uncertainties inherent in clinical trials and product development programs, including but not limited to the fact that pre-clinical and clinical results may not be indicative of results achievable in other trials or for other indications, that results from one study may not necessarily be reflected or supported by the results of other similar studies, that results from an animal study may not be indicative of results achievable in human studies, that clinical testing is expensive and can take many years to complete, that the outcome of any clinical trial is uncertain and failure can occur at any time during the clinical trial process, and that Inovio’s electroporation technology and DNA vaccines may fail to show the desired safety and efficacy traits in clinical trials; all product candidates that Inovio advances to clinical testing will require regulatory approval prior to commercial use, and will require significant costs for commercialization; the availability of funding; the ability to manufacture vaccine candidates; the availability or potential availability of alternative therapies or treatments for the conditions targeted by Inovio or its collaborators, including alternatives that may be more efficacious or cost-effective than any therapy or treatment that Inovio and its collaborators hope to develop; whether Inovio’s proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity; and the impact of government healthcare proposals. Readers are also referred to Inovio’s Annual Report on Form 10-K for the year ended December 31, 2009 and other regulatory filings filed with the Securities and Exchange Commission which identify important risk factors that could cause actual results to differ from those contained in the forward-looking statements.
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