Inovio Pharmaceuticals, Inc. (NYSE Amex: INO), 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 Gynecology-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-γ 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 centers 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 analyzed for evidence of immune responses in the cervix at baseline and subsequent intervals. Subjects will also be monitored for tolerability and safety.
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