Therapeutic HPV-16/18 Vaccine Produces Regression of Cervical Intraepithelial Neoplasia Grade 2/3 in Phase II Trial
In a phase IIb trial reported in The Lancet, Trimble et al found that a therapeutic synthetic vaccine (VGX-3100) targeting human papillomavirus (HPV) 16 and 18 E6 and E7 proteins increased the frequency of regression of HPV-16/18–related cervical intraepithelial neoplasia grade 2/3 vs placebo.
Study Details
In the double-blind trial, 167 women with cervical intraepithelial neoplasia grade 2/3 from 36 academic and private gynecology practices in seven countries were randomly assigned 3:1 between October 2011 and July 2013 to receive VGX-3100 at 6 mg (n = 125) or placebo at 1 mL (n = 42) given intramuscularly at 0, 4, and 12 weeks.
The primary efficacy endpoint was regression to cervical intraepithelial neoplasia grade 1 or normal pathology at 36 weeks after the first dose. Per-protocol and modified intention-to-treat analyses were based on patients receiving three doses without protocol violations and on patients receiving at least one dose.
Regression Rates
In the per-protocol analysis, histopathologic regression was observed in 49.5% of the VGX-3100 group vs 30.6% of the placebo group (absolute difference = 19.0%, 95% confidence interval [CI] = 1.4%–36.6%, P = .034). In the modified intention-to-treat analysis, regression was observed in 48.2% vs 30.0% (absolute difference = 18.2%, 95% CI = 1.3%–34.4%, P = .034).
Adverse Events
Injection-site reactions occurred in most patients, with only erythema occurring with significantly greater frequency in the VGX-3100 group (78.4% vs 57.1%, P = .007). Grade 3 adverse events occurred in 4.8% vs 2.4% of patients. There were no serious adverse events. Treatment was discontinued due to adverse events in 2.4% of each group.
The investigators concluded: “VGX-3100 is the first therapeutic vaccine to show efficacy against [cervical intraepithelial neoplasia grade 2/3] associated with HPV-16 and HPV-18. VGX-3100 could present a non-surgical therapeutic option for [cervical intraepithelial neoplasia grade 2/3], changing the treatment outlook for this common disease.”
Cornelia L. Trimble, MD, of Johns Hopkins University School of Medicine, is the corresponding author for the Lancet article.
The study was funded by Inovio Pharmaceuticals. For full disclosures of the study authors, visit www.thelancet.com.
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