Inovio Pharmaceuticals, Inc., a leader in the development of therapeutic and preventive vaccines against cancers and infectious diseases, announced today that it is initiating a Phase II clinical trial for its VGX-3100 DNA vaccine for cervical dysplasia and cancer caused by human papillomavirus (HPV).
The study will assess adult females with CIN 2/3 or CIN 3 and biopsy-proven HPV 16 or 18. Cervical intraepithelial neoplasias (CIN) are pre-cancerous stages of abnormal cells that precede cervical cancer. HPV types 16 and 18 are responsible for 70% of CIN 2/3 and cervical cancer incidences. The randomized, placebo-controlled, double-blind study will evaluate cervical tissue changes after three 6 mg doses of VGX-3100 are administered by injection in combination with Inovio's CELLECTRA®electroporation delivery device. A total of 148 patients will be enrolled in 25 study centers in the US, Korea, South Africa,Australia, and Canada.
The primary endpoints of this study are to assess regression of cervical lesions to CIN 1 or less and clearance of HPV 16 or 18. The study will evaluate the efficacy of the vaccine in patients who receive VGX-3100 at 0, 4 and 12 weeks compared to placebo recipients, based on a biopsy performed six months after the final vaccine dose.
The study will also explore 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 the beginning of the trial and subsequent intervals. Subjects will also be monitored for tolerability and safety. The clinical trial protocol, HPV-003, is available at: http://clinicaltrials.gov/ct2/show/NCT01304524?term=NCT01304524&rank=1.
This Phase II trial is a follow-on to Inovio's Phase I dose escalation study of VGX-3100, which achieved best-in-class immune responses. In that study, 13 out of 18 vaccinated subjects (72%) developed significant T-cell responses, with positive responses ranging from under 100 to over 5000 SFU per million cells. In the third and highest dose group, 83% (5 of 6) had strong T-cell responses. In addition, 15 of 18 vaccinated subjects (83%) developed antibody responses to at least one antigen with most subjects developing responses to two or more antigens. No DNA vaccine has previously achieved this rate of response.
Dr. J. Joseph Kim, Inovio's president and CEO, said: "The initiation of this cancer vaccine trial is a milestone for Inovio. This is the first Phase II trial with an internally developed SynCon™ DNA vaccine, indicating the growing maturity of our product pipeline. We are encouraged by the precedent set in achieving demonstrable clinical efficacy by other vaccines in clinical development using different vaccine platforms targeting these antigens. VGX-3100 vaccine has demonstrated best-in-class immune responses and we look forward to the potential translation of those results into improved clinical efficacy."
About Cervical Dysplasias/Cancers and Inovio's Therapeutic DNA Vaccine
Human papillomavirus (HPV) is the causative agent responsible for most cases of cervical cancer. At any given time, approximately 10% of women worldwide are infected with HPV. While roughly 70% of HPV infections are cleared by the body on its own, persistent HPV can lead to dysplasia, or premalignant changes in cells, of the cervix. Researchers have estimated the global prevalence of clinically pre-cancerous HPV infections at between 28 and 40 million. Persistent dysplasias may then progress to cancer. Every year, 510,000 cases of cervical cancer are diagnosed worldwide, and about 288,000 of the afflicted women, primarily in developing countries, die.
Preventive vaccines such as GARDASIL® and CERVARIX® are playing an important role in limiting new HPV infections. However, preventive vaccines cannot provide protection for those already infected, which is a large population. In addition, a significant number of the girls and women eligible to be vaccinated are not receiving these preventive vaccines. There is no viable therapeutic vaccine or drug to fight HPV, nor dysplasias and cancers caused by HPV. Current ablative or surgical procedures to remove cervical dysplasias and cancers are unappealing due to their potential for disfigurement, the perceived negative impacts on childbirth, and the stress of the watch-and-wait approach that typically precedes these procedures.
HPV types 6, 11, 16 and 18 are responsible for 35 – 50% of the 1.4 million low-grade CIN 1 dysplasias diagnosed annually in the US, while types 16 and 18 are responsible for about 70% of the 300,000 high grade CIN 2/3 dysplasias and cervical cancer incidences. Inovio's VGX-3100 is designed to raise immune responses against the E6 and E7 oncogenes common to HPV types 16 and 18. These oncogenes are responsible for transforming HPV-infected cells into pre-cancerous 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 from the body. The potential of such a therapeutic vaccine would be to treat pre-cancerous dysplasias (CINs), cervical cancers, as well as other anogenital and head and neck cancers caused by these HPV types.
