Inovio Pharmaceuticals, Inc. a leader in the development of therapeutic and preventive vaccines against cancers and infectious diseases, has reported data demonstrating long-term durability of immune responses induced by VGX-3100, its investigational DNA vaccine for treating cervical dysplasia and cancer caused by Human Papillomavirus (HPV). These results were presented at the 15th Annual Conference on Women's Health Care Issues, hosted in New York by the International Infectious Disease Society for Obstetrics and Gynaecology-USA, by Mark Bagarazzi, MD, Inovio's chief medical officer.

The data were generated through a long-term assessment of participants in Inovio's phase I study of 18 adult females with moderate or severe Cervical Intraepithelial Neoplasia (CIN 2/3), a high-grade premalignant lesion that may lead to cervical cancer. This study was designed to assess immune responses generated by and safety of the vaccine.

In this study, 72% of vaccinated subjects (13 of 18) developed significant antigen-specific T-cell responses during the first four months of treatment (each patient was vaccinated at months 0, 1, and 3) by standardized interferon-? ELISpot assay. The third and highest dose group displayed the strongest level of T cell responses, with 83% (5 of 6) positive responders. The level of T cell responses in positive responders ranged from 100 to over 5000 Spot Forming Units (SFU) per million cells when measured after overnight stimulation in the standardized ELISpot assay. In contrast, competing vaccine approaches targeting HPV therapy have consistently shown sub-100 SFU levels even when using more sensitive assays.

This newly reported data evaluated 11 of 13 positive responders as well as 3 of 5 patients who were non-responders at month 4. These patients were subsequently monitored through to study completion at month 9 (six months post last vaccination). As expected, all three non-responders at month 4 still did not show a T cell response at month 9. In contrast, 91% of evaluated patients (10 of 11) displayed strong and persistent memory T-cell responses at month 9. Importantly, the level of T cell responses remained strong, with responses ranging from 100 to over 3800 SFU. These results are consistent and add validation to similar levels of persistent and strong T cell responses at month 9 observed by Inovio from its Pennvax HIV vaccine studies in non-human primates.

Generation of T cell responses is considered instrumental in clearing cancerous cells from the body and imperative to achieving sufficient potency of new therapeutic vaccines against cancers. Achieving a sustained, durable immune response provides the prospect that the body will maintain a prolonged vigilance and fight against precancerous and cancerous cells of the cervix. Such persistent memory T cell responses previously have not been reported using other vaccine platforms, including competing viral vector programs. Additionally, the sustained T cell responses at month 9 reported here are at least ten-fold higher than those presented by competing vaccine candidates even at their peak short-term level.

“These results demonstrate the powerful potential of our SynCon VGX-3100 vaccine delivered using our proprietary Cellectra electroporation system as well as the capabilities of our proprietary vaccine platform,” said Dr J Joseph Kim, Inovio's president and CEO.

“Based on the compelling data achieved from our phase I cervical dysplasia clinical study, we are now evaluating the efficacy of VGX-3100 delivered using our Cellectra electroporation device in a randomized, placebo-controlled, double-blind phase II clinical study. We believe that these newly reported phase I data showing long term persistence of antigen-specific T cells further support our confidence and optimism for ultimately meeting the primary endpoint of this phase II efficacy study: the clearance of CIN 2/3 lesions, measured at month 9, after three vaccinations at months 0, 1, and 3,” concluded Dr Kim.  

This recently initiated phase II study will enroll 148 patients with CIN 2/3 or CIN 3 at approximately 25 study centres in the US, Korea, South Africa, Australia, and Canada. The study will also assess humoral and cell mediated immune responses to VGX-3100 in blood samples taken prior to the first vaccine dose and periodically thereafter. Cervical samples will be analysed for evidence of immune responses in the cervix at baseline and subsequent intervals. Subjects will also be monitored for tolerability and safety.

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, primarily in developing countries, 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 fight 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 and cervical cancer incidences.

Inovio's VGX-3100 is designed to raise immune responses against the E6 and E7 oncogenes common to HPV types 16 and 18. 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 anogenital and head and neck cancers caused by these HPV types.

Inovio is developing a new generation of vaccines, called DNA vaccines, to treat and prevent cancers and infectious diseases. Its SynCon vaccines are designed to provide broad cross-strain protection against known as well as newly emergent strains of pathogens such as influenza. These vaccines, in combination with Inovio's proprietary electroporation delivery devices, have been shown to be safe and generate significant immune responses.