Vaccine: VGX-3100
Company: Inovio Pharmaceuticals
Target: Cervical cancer

The human papillomavirus (HPV), which is behind 90% or more of cases of cervical cancer, has been the target for preventive vaccines for a while, with shots such as Merck's ($MRK) Gardasil and GlaxoSmithKline's ($GSK) Cervarix in third and 8th place in the 20 top-selling vaccines of the first half of 2012. Treating cervical cancer in its earliest stages, when doctors spot precancerous changes in the cervix, is the next target for vaccines, and Inovio Pharmaceuticals ($INO) has created a DNA vaccine, VGX-3100, for this indication, which is currently in a global Phase II clinical trial.

VGX-3100, one of the company's SynCon vaccines, targets HPV-16 and HPV-18, two strains that are responsible for about 70% of cases of cervical cancer. The SynCon synthetic vaccines include a fragment of DNA that codes for an antigen. One of the issues with DNA vaccines is getting the DNA inside the target cell. Inovio uses electroporation--a small electric charge that loosens up the cell membrane to let the vaccine through.

Inovio's VGX-3100 is designed to raise immune responses against the E6 and E7 oncogenes associated with HPV types 16 and 18, i.e., it targets four antigens. These oncogenes are responsible for transforming HPV-infected cells into precancerous 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. The potential of such a therapeutic vaccine would be to treat precancerous dysplasias (cervical intraepithelial neoplasias or CINs), cervical cancers, as well as other cancers caused by these HPV types such as head and neck and anogenital cancers.

In a Phase I proof-of-concept study, published in Science Translational Medicine, 18 women who had previously been treated for precancerous changes in the cervix (cervical intraepithelial neoplasia grade 2 or 3 [CIN 2/3]) were given Inovio's vaccine. All 18 patients showed an immune response to the vaccine, and in 14 of the 18 (78%), the vaccine triggered a T-cell response (the cells responsible for cell-mediated immunity). More than 90% of these patients had a subset of T cells, so-called killer T cells or CD8+ T cells, that had the capability of killing HPV-infected cells, and T-cell responses were still seen in the blood in most patients at least 6 months after the last vaccination.

According to the company, this is the first time that a DNA-based therapeutic vaccine has produced immune responses that can kill target cells. This is only a small study, but it obviously had an impact on the investment community: The stock jumped more than 16% on the news, although it is still only trading around 70 cents per share.

A Phase II efficacy study is ongoing, with results expected next year. This again involves women with CIN 2/3 cervical lesions, and is looking for improvement to CIN 1 or complete regression, as well as clearance of HPV-16 and HPV-18. VGX-3100 also featured in our 2011 edition of 10 promising therapeutic vaccines.

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