Inovio Pharmaceuticals, a developer of therapeutic and preventive vaccines against cancers and infectious diseases, has reported long-term durability of T cell immune responses of up to over two years (at the latest time measured) in seven of eight evaluated patients following a fourth vaccination of VGX-3100, its investigational SynConR 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.
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 CELLECTRAR 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 13 were injected with a fourth dose of 6mg of VGX-3100, regardless of the original dose they received (0.6mg (0.3mg each of two DNA plasmids), 2.0mg or 6.0mg).
To date, of eight of 13 patients analyzed, seven of eight (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 U.S., 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.