Inovio Pharmaceuticals Inc. announced successful results from its randomized, double-blind, placebo-controlled Phase 2 trial of VGX-3100 in women with biopsy-proven cervical intraepithelial neoplasia 2/3 (CIN2/3) associated with human papillomavirus (HPV) types 16 or 18. Treatment with VGX-3100, Inovio’s HPV16/18-specific immunotherapy, resulted in histopathological regression of CIN2/3 to CIN1 or no disease, meeting the study’s primary endpoint. In addition, the trial demonstrated clearance of HPV in conjunction with regression of cervical lesions. Robust T-cell activity was detected in subjects who received VGX-3100 compared to those who received placebo.
“This is a significant step toward providing women and their physicians a non-surgical approach to the treatment of precancerous lesions by stimulating their immune system to eliminate high risk HPV infection and induce regression of a cervical intraepithelial neoplastic process,” said Mark Bagarazzi, chief medical officer, Inovio Pharmaceuticals. “This proof of concept trial will guide the advancement of VGX-3100 for precancerous dysplasias as well as HPV-associated cervical, head and neck, and anogenital cancers.”
Treatment was randomized 3:1 between the VGX-3100 and placebo groups, and was stratified by age and severity of CIN. The primary endpoint, histologic regression, was evaluated 36 weeks after the first treatment. In the per protocol analysis, CIN2/3 resolved to CIN1 or no disease in 53 of 107 (49.5%) women treated with VGX-3100 compared to 11 of 36 (30.6%) who received placebo. This difference was statistically significant (p<0.025).
Virological clearance of HPV 16 or 18 from the cervix in conjunction with histopathological regression of cervical dysplasia to CIN1 or no disease, a secondary endpoint of the trial, was observed in 43 of 107 (40.2%) VGX-3100 recipients compared to five of 35 (14.3%) placebo recipients (p<0.025).
As in the Phase 1 study, VGX-3100 elicited robust HPV-specific T-cell responses in the majority of treated subjects. A comprehensive analysis of T-cell responses is ongoing.
The treatment was generally well-tolerated, with only administration site redness occurring significantly more frequently in the VGX-3100 group compared to the placebo group in the seven- and 28-day periods following treatment.
“Beyond the direct clinical implications of this Phase 2 study, these results are a breakthrough for the field of immunotherapies. This efficacy and T cell data provide evidence that our SynCon immunotherapy technology can activate the immune system to fight chronic infections, pre-cancers— and ultimately, cancers,” said Dr. J. Joseph Kim, Inovio’s president and CEO. “These results significantly de-risk our product and business development strategy for VGX-3100 and our broad pipeline of SynCon® active immune therapy and vaccine products.
“We thank the women who participated and the clinical investigators who provided patient care and made this trial possible,” Kim said.
Topline results were presented Wednesday at the 2014 International Society of DNA Vaccines Conference in San Diego. Detailed study findings will be submitted for publication in a peer-reviewed scientific journal.
Date: July 23, 2014