Inovio Pharmaceuticals, USA
Title: VGX-3100 drives regression of HPV16/18 CIN2/3 and robust cellular immune responses in blood and cervical tissue in a blinded, randomized, placebo-controlled phase 2b study
Biography: Prakash Bhuyan
Objectives: Assessment of the safety, efficacy and immunogenicity of VGX-3100 in women with biopsy-proven CIN2/3 with HPV16 and or HPV18 infection.
\r\n\r\n\r\n\r\nMethods: Randomized, placebo-controlled, double-blind study, stratified by age and severity of CIN, evaluated cervical tissue changes after three 6 mg intramuscular doses of VGX-3100 followed by electroporation with Inovio’s CELLECTRA®2000 device at weeks 0, 4 and 12.
\r\n\r\nResults: Among 167 vaccinated women, the study met its primary efficacy endpoint; the percentage of patients who had regression of CIN2/3 to CIN1 or no disease at 6 months post third dose was significantly higher in VGX-3100 recipients compared to placebo (p=0.034). VGX-3100 cleared HPV16/18 infection concurrent with regression of CIN2/3 (p=0.003). Post-hoc immune analysis revealed significantly elevated immune responses in treated patients who had CIN2/3 regression concurrent with HPV16/18 clearance when compared to those who did not. This included the presence of CD8+ T-cells in the blood exhibiting CD137 expression concurrent with perforin (p=0.032) as well as perforin in addition to granzyme A (p=0.036) as well as an influx of CD8+ T-cells into cervical tissue (p=0.008).
\r\n\r\nConclusion: The successful phase 2b results represent a significant milestone in the development of active immunotherapies to treat HPV-related dysplasia and cancer. The data generated from the trial reveal a significant clinical benefit afforded by treatment with VGX-3100 and underscore the mechanism of action of HPV specific T cells. Thus VGX-3100 has the potential to provide an important alternative or adjunct to surgery in treating CIN 2/3.