Agenus Inc., a developer of therapeutic vaccines for cancer and infectious diseases, has reported significant top-line results from its phase II randomized, double-blind, multi-centre study for HerpV, a recombinant “off-the-shelf” therapeutic vaccine candidate for the treatment of patients with herpes simplex virus-2 (HSV-2). HerpV contains a defined mixture of peptides representing HSV-2 antigens plus Agenus’ QS-21 Stimulon adjuvant.

This phase II study tested the biological efficacy of HerpV measuring genital viral shedding 45 days before and after three injections of HerpV. The primary analysis, which looked at viral shedding after the initial three injections, shows that subjects who received HerpV had a statistically significant reduction in viral shedding (P=0.015; RR=0.85). These results suggest a 15 per cent reduction in viral shedding after the initial treatment period before the administration of the booster injection. The results also demonstrate a reduction in viral load of 34 per cent (P=0.08). Placebo patients showed no reduction compared to baseline in either parameter. Notably, patients were not on any antiviral treatments during their swabbing period. The initial data support that vaccination with HerpV has a real, measurable biological effect lowering the active shedding of the virus.

The majority of subjects in the study have received a booster injection of HerpV that was given six months after the first vaccination followed by determination of genital viral shedding for an additional 45-day period. Post-booster viral shedding results, along with immune response data, are anticipated in the first half of 2014.

“These data are exciting as we are finally seeing that we can direct the immune system to fight this disease,” said the study’s lead principal investigator, Anna Wald, MD, Professor of Allergy and Infectious Diseases, University of Washington. “These HerpV data confirm that immune therapy may be an effective intervention in genital herpes; as such this is an exciting new finding.”

“These data are exceedingly promising as this is one of the first HSV vaccine trials to demonstrate a reduction in viral shedding and trends in decreasing viral load,” said Richard Whitley, MD, Professor of Paediatrics, University of Alabama at Birmingham. “I am pleased to see this progress given the significant need for new treatment options for managing HSV-2 disease and its transmission on a global level.”

The HerpV phase II study design was defined by key opinion leaders in the field. Experts in HSV-2 clinical research believe that a reduction in viral shedding is an important surrogate for clinical benefit in the form of reduction in recurrent outbreaks.

A total of 80 subjects with a history of one to nine herpes recurrences within the prior 12 months were randomized into the trial and 70 subjects received the active treatment, HerpV and QS-21 Stimulon, and 10 subjects received placebo. Three injections of HerpV at a dose of 240µg (includes 12µg of 32 different HSV-2 associated peptides) or placebo were given at 2 week intervals with a 45 day genital swabbing period before and after the vaccination period. Swabs were sent to the laboratory at the University of Washington for PCR analysis of HSV-2 virus.

The top-line, pre-booster PCR data show that subjects who received HerpV had a statistically significant reduction in viral shedding after three vaccinations in comparison to baseline (P=0.015) with a relative risk reduction of 0.85. In the small group of subjects who received placebo there was no reduction in viral shedding (P=0.96). Agenus expects to carry out a more complete assessment of efficacy and immunologic response when the post-booster viral swabbing data are available, which is anticipated during the first half of 2014. In this study, the vaccine candidate was generally well tolerated.

Agenus’ flagship adjuvant, QS-21 Stimulon, is a saponin extracted from the bark of the Quillaja saponaria tree, also known as the soap bark tree, an evergreen tree native to warm temperate central Chile. QS-21 Stimulon has become a key component of vaccines intended to prevent a wide variety of infectious diseases and to treat cancers and degenerative disorders. It is currently being studied in clinical trials for approximately 21 vaccine indications, and over 50,000 patients have now received vaccines candidates containing the adjuvant. GlaxoSmithKline is a key licensee and their phase III vaccine programmes include RTS,S for malaria, MAGE-A3 cancer immunotherapeutic for non-small cell lung cancer and melanoma and HZ/su for shingles. In addition, Janssen’s QS-21 Stimulon-containing vaccine candidate is in phase II trials for the treatment of Alzheimer’s disease.