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 T cell immune responses of up to over two years (at the latest time measured) in 7 of 8 evaluated patients following a fourth vaccination of VGX-3100, its investigational SynCon® DNA vaccine for treating cervical dysplasia and cancer caused by human papillomavirus (HPV) that is delivered using intramuscular electroporation. The data further highlights the viability of using multiple booster vaccinations with a DNA vaccine delivered using electroporation, in contrast to other non-replicating vaccine vectors that may induce unwanted immune responses against the vector after multiple vaccinations. These results were presented at DNA Vaccines 2011, hosted in San Diego by the International Society of DNA Vaccines, by Mark Bagarazzi, MD, Inovio's Chief Medical Officer.
"Achieving long-lasting immune responses exceeding two years is exceptional," said Dr. J. Joseph Kim, Inovio's president and CEO. "In general, the durability of these T cell responses places Inovio's DNA vaccine technology on par with live virus vaccines, but without their various safety and other issues, and substantially exceeds current data from alternative non-replicating vaccine technologies. Furthermore, being able to use multiple vaccinations without safety concerns or unwanted immune responses is a notable advantage of Inovio's DNA vaccine technology."
"There is no therapeutic live virus vaccine nor non-replicating vaccine for cervical dysplasias and cancers in the market, so Inovio's DNA vaccine for cervical dysplasias/cancer answers an unmet need by providing a non-invasive and potentially more effective approach for treating these diseases. Additionally, with respect to any disease that requiring sustained T-cell responses to provide protection or fight the disease, such as hepatitis C virus and HIV, these strong durable immune responses are promising."
Inovio's original phase I, designated HPV-001, treated 18 women who had previously been diagnosed with and surgically treated for high grade cervical intraepithelial neoplasia (CIN 2/3), a premalignant lesion that may lead to cervical cancer, with a three-vaccination regimen of its VGX-3100 therapeutic DNA vaccine delivered with its CELLECTRA® electroporation device. In a longer-term analysis of T cell responses by ELISpot at nine or more months after the initial vaccination (> six months post last vaccination), of 13 initially responding patients, 12 (92%) had maintained significant T cell responses nine to 19 months after their first vaccination. One subject that did not respond early on remained a non-responder. Importantly, the level of T cell responses remained strong.
Inovio then initiated this follow-on study, designated HPV-002, with the intent to assess safety and immune responses following a fourth vaccination. Of the original 18 subjects, 11 T-cell responders and two non-responders were eligible and agreed to participate. All thirteen were injected with a fourth dose of 6 mg of VGX-3100, regardless of the original dose they received (0.6 mg (0.3 mg each of two DNA plasmids), 2.0 mg, or 6.0 mg).
To date, of 8 of 13 patients analyzed, 7 of 8 (87%) patients displayed strong T-cell responses that have persisted for up to over two years. One patient that had a negative T-cell response prior to the fourth vaccination remained negative. Response magnitudes remain high and three subjects are responding to additional antigens (among the four antigens encoded by the vaccine) that they were not previously responding to prior to this fourth vaccination.
Inovio is now recruiting for its Phase II study, which is designed to enroll 148 patients with CIN 2/3 or CIN 3 at approximately 25 study centers in the US, Korea, South Africa, Australia, and Canada. This randomized, placebo-controlled study will assess histopathological response to vaccination as the primary endpoint as well as humoral and cell mediated immune responses to VGX-3100. Cervical samples will be analyzed for evidence of immune responses in the cervix. Subjects will also be monitored for tolerability and safety. See the Phase II clinical trial protocol for HPV-003.
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