BLUE BELL, Pa., Oct. 10, 2012 /PRNewswire/ -- Inovio Pharmaceuticals, Inc. (NYSE MKT: INO) announced today clinical results indicating that its VGX-3100 therapeutic synthetic vaccine is capable of not only driving robust immune responses to antigens from high risk types of human papillomavirus (HPV) infection but that these immune responses displayed a powerful killing effect on cells changed by HPV into precancerous dysplasias. This desirable effect may ultimately contribute to the regression or elimination of cervical dysplasia and cervical cancer. Inovio is currently assessing the ability of its DNA-based VGX-3100 to treat cervical dysplasias caused by HPV infection in a global phase II trial.
Results from this phase I trial appeared today in the peer-reviewed journal, Science-Translational Medicine, in an article entitled, "Immunotherapy against HPV 16/18 generates potent Th1 and cytotoxic cellular immune responses."
The paper reports that 100% of patients (18 of 18) enrolled in the phase I dose-escalating trial showed antigen-specific antibody responses to Inovio's vaccine, while 78% showed T-cell responses in the validated ELISpot assay. Further tests of T-cell immunity measured the ability of CD8+ T-cells from vaccinated patients to kill cells displaying HPV antigens on their surface: 91% of patients who developed T-cell responses showed the presence of CD8+ T-cells capable of this type of killing activity (so-called "killer T-cells"), which is believed to be critical for the treatment of cervical dysplasia and ultimately cancer caused by HPV.
Dr. J. Joseph Kim, Inovio's President and CEO, said, "Today's milestone is convincing evidence that a DNA-based immune therapy can generate potent and durable T-cell responses in people. Our ongoing phase II efficacy trial is designed to show that the immune responses seen in this study, in particular the generation of killer T-cell responses, may reverse cervical disease caused by chronic HPV infection."
"The type of T-cell killing activity seen in this new data provides a growing foundation for efficacy trials focused on the treatment of HPV-associated cancers including cervical, head and neck, and anogenital cancers," Dr. Kim added.
Scientific discussion of trial results
Overall, 100% of the study participants (18 of 18) reported antibody positivity to at least two vaccine antigens, and 94% (17 of 18) reported positivity to three antigens; 56% (10 of 18) were positive to all four antigens.
Similarly, a deeper ELISpot analysis of the T-cell immune data showed that 78% (14 of 18) subjects showed T-cell responses to at least one vaccine antigen, 72% (13 of 18) responded to at least two antigens, and 50% (9 of 18) responded to all four antigens. Moreover, analysis of T-cell immune data 24 weeks after the last immunization showed that the responses were still detectable in 86% of evaluable patients, indicating that T-cell responses, in addition to antibody responses, persist for at least 6 months after the final immunization at month 3.
The investigators also undertook a more detailed analysis of antigen specific cytotoxic T-lymphocyte (CTL/killer T-cell) activity in the CD8+ T-cells from the high dose cohort of vaccinated subjects by measuring the expression of biologic markers like granzyme B and perforin (proteins that are known to be important in killing) as well as the direct killing of cells displaying HPV antigens on their surface through the release of granzyme B from the CTLs. Results presented in the paper show that these patients showed a significant increase in the amount of granzyme B and perforin found within their CTLs, and direct killing by CTLs was observed in all vaccinated subjects (6 of 6) in the high dose cohort. These results suggest that immunization with VGX-3100 generated CD8+ T-cells that were capable of making granzyme B and perforin upon seeing HPV antigens, and that these CD8+ T-cells were able to effectively use the granzyme B and perforin to kill cells displaying HPV antigens on their surface - a clear indication of the presence of a functional CTL/killer T-cell response.
Phase II efficacy study on-going
Inovio continues patient recruitment for its phase II study of VGX-3100, which is designed to enroll 148 patients with cervical dysplasia at multiple study centers. This randomized, double-blinded, placebo-controlled study will assess regression of cervical lesions from CIN 2/3 or CIN 3 to CIN 1 or complete regression of the lesions. The secondary endpoint is to assess the clearance of HPV 16 or 18. Subjects will also be monitored for tolerability and safety. Inovio expects results from this trial late next year. See the HPV-003 clinical trial protocol.
About Cervical Dysplasias/Cancers
Human papillomavirus (HPV) is the causative agent responsible for most cases of cervical cancer. At any given time, approximately 10% of women worldwide are infected with HPV. While roughly 70% of HPV infections are cleared by the body on its own, persistent HPV can lead to dysplasia, or premalignant changes in cells, of the cervix. Researchers have estimated the global prevalence of clinically pre-cancerous HPV infections at between 28 and 40 million. Persistent dysplasias may then progress to cancer. Every year, 510,000 cases of cervical cancer are diagnosed worldwide, and about 288,000 of the afflicted women die.
Preventive vaccines such as GARDASIL® and CERVARIX® are playing an important role in limiting new HPV infections. However, preventive vaccines cannot provide protection for those already infected, which is a large population. In addition, a significant number of the girls and women eligible to be vaccinated are not receiving these preventive vaccines. There is no viable therapeutic vaccine or drug to treat HPV, nor dysplasias and cancers caused by HPV. Current ablative or surgical procedures to remove cervical dysplasias and cancers are unappealing due to their potential for disfigurement, the perceived negative impacts on childbirth, and the stress of the watch-and-wait approach that typically precedes these procedures.
HPV types 6, 11, 16 and 18 are responsible for 35% to 50% of the 1.4 million low-grade CIN 1 dysplasias diagnosed annually in the US. HPV types 16 and 18 are responsible for about 70% of the 300,000 high grade CIN 2/3 dysplasias as well as cervical cancer incidences.
Inovio's VGX-3100 is designed to raise immune responses against the E6 and E7 oncogenes associated with HPV types 16 and 18, i.e. it targets four antigens. These oncogenes are responsible for transforming HPV-infected cells into pre-cancerous and cancerous cells. The goal is to stimulate a T-cell immune response strong enough to cause the rejection of these infected or transformed cells from the body. The potential of such a therapeutic vaccine would be to treat precancerous dysplasias (CINs), cervical cancers, as well as other cancers caused by these HPV types such as head and neck and anogenital cancers.
About Inovio Pharmaceuticals, Inc.
Inovio is revolutionizing vaccines to prevent and treat today's cancers and challenging infectious diseases. Its SynCon® vaccines are designed to provide universal cross-strain protection against known as well as newly emergent unmatched strains of pathogens such as influenza. These synthetic vaccines, in combination with Inovio's proprietary electroporation delivery, have been shown in humans to generate best-in-class immune responses with a favorable safety profile. Inovio's clinical programs include phase II studies for cervical dysplasia, leukemia and hepatitis C virus and phase I studies for influenza and HIV. Partners and collaborators include the University of Pennsylvania, Merck, ChronTech, National Cancer Institute, U.S. Military HIV Research Program, NIH, HIV Vaccines Trial Network, University of Southampton, US Dept. of Homeland Security and PATH Malaria Vaccine Initiative. More information is available at www.inovio.com.
This press release contains certain forward-looking statements relating to our business, including our plans to develop electroporation-based drug and gene delivery technologies and DNA vaccines and our capital resources. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials and product development programs (including, but not limited to, the fact that pre-clinical and clinical results referenced in this release may not be indicative of results achievable in other trials or for other indications, that the studies or trials may not be successful or achieve the results desired, that pre-clinical studies and clinical trials may not commence or be completed in the time periods anticipated, that results from one study may not necessarily be reflected or supported by the results of other similar studies and that results from an animal study may not be indicative of results achievable in human studies), 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 vaccines, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by the company or its collaborators, including alternatives that may be more efficacious or cost-effective than any therapy or treatment that the company and its collaborators hope to develop, evaluation of potential opportunities, issues involving product liability, issues involving patents and whether they or licenses to them will provide the company 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 the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of the company's technology by potential corporate or other partners or collaborators, our ability to secure new partnerships and collaborations, 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, 2011, our Form 10-Q for the quarter ended June 30, 2012, and other regulatory filings from time to time. There can be no assurance that any product in Inovio's pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate.
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