Inovio Biomedical Corporation, a leader in DNA vaccine design, development and delivery, has completed enrolment of all subjects for its therapeutic cervical cancer vaccine (VGX-3100) phase-I trial. VGX-3100 is a DNA vaccine targeting the E6 and E7 proteins of human papillomavirus (HPV) types 16 and 18, and is delivered via in vivo electroporation.
This dose escalation study was designed to test the safety and immunogenicity of VGX-3100 in women with a previous history of cervical intraepithelial neoplasia (CIN) 2/3, a precursor lesion prior to the development of cancer. The trial enrolled patients in three cohorts of six subjects each with DNA vaccine doses at 0.6 mg (0.3 mg for each of two DNA plasmids), 2.0 mg, and 6.0 mg. The immunization regimen consists of each subject receiving the respective dose at day 0, month 1 and month 3. The vaccine is delivered using Inovio's proprietary Cellectra intramuscular electroporation delivery device.
All twelve patients from the first two dose cohorts have been evaluated for safety and immune responses. The vaccine has been well tolerated with an acceptable safety profile in all subjects tested. In general, reported adverse events and injection site reactions were mild to moderate and required no treatment.
The interim immunological analysis of blood samples collected before and after vaccination indicated the induction of antigen-specific immune responses against the target proteins produced by the vaccine. Antigen-specific cytotoxic T-lymphocyte (CTL) responses were observed against all four antigens (E6 and E7 proteins for HPV types 16 and 18).
In the first two cohorts, 6 of 12 vaccinated subjects (50%) developed significant CTL responses, with average CTL responses increasing in a dose-related fashion. Generation of tumour-specific T-cell responses is believed to be an important characteristic of a cancer therapeutic vaccine.
Inovio also tested the samples for antibody responses against the target antigens and observed strong antibody responses in 10 of 12 subjects (83%). Antibodies were generated against all four antigens, as tested by the enzyme-linked immunosorbent assay (ELISA). Moreover, the level of antibody responses in the second, mid-dose cohort was on average 5 - 10 fold higher than that observed in the lowest-dose cohort. The high antibody titers achieved in this study have not previously been observed in human clinical trials of other DNA immunogens.
Specific antibody responses to tumour antigens can function as an important surrogate potency marker for determining the immunogenicity of a vaccine, i.e. the ability of a vaccine to induce an immune response. Furthermore, Inovio believes these results further validate the usefulness of its DNA vaccine platform against infectious disease targets, where generation of antibodies has been shown to be protective.
"We are pleased to report the completion of enrolment for the VGX-3100 study. We have been working diligently to progress this program forward. The interim analyses of the vaccinated subjects from the first two cohorts indicate that our vaccine is highly immunogenic, generating antigen-specific T-cell and antibody responses that are amongst the highest reported from any previous human studies of DNA vaccines," stated Dr J Joseph Kim, president and CEO.
"While VGX-3100 is a potentially important product against cervical cancer, we believe a successful completion of this study will mark an important event for our field as a whole and a strong valuation enhancing event for our company," Dr Kim added.
Inovio Biomedical is focused on the design, development, and delivery of a new generation of vaccines, called DNA vaccines, to prevent and treat cancers and infectious diseases.