Barinthus' HPV therapy proves safety, but not efficacy

Barinthus Biotherapeutics has hit the primary endpoint of a phase 1b/2 trial by showing its treatment for high-risk human papillomavirus (hrHPV) is safe. But the failure to prove the therapy actually works has left the biotech mulling how to take the candidate further.

The trial involved 108 women across the U.K. and the EU aged 25 to 55 with persistent hrHPV infection and low-grade cervical lesions who received either the therapy, dubbed VTP-200, or placebo. VTP-200 is an immunotherapeutic combo regimen that involves patients receiving an initial dose using the ChAdOx vector and a second dose using the MVA vector. Both doses encode the same HPV antigens, with the aim of producing an antigen-specific T-cell immune response to HPV.

The U.K.-based company—formerly known as Vaccitech—said the trial hit its primary endpoint of demonstrating VTP-200 was generally safe and well tolerated. No treatment-related adverse events of grade 3 or above were recorded.

However, when it came to whether the immunotherapeutic actually works, things weren’t as straightforward. Barinthus was keen to zoom down into the five groups who had received different variations of the VTP-200 combo regimen to try to salvage some success.

For example, in group 2—which included the highest dose of ChAdOx—there was a hrPV clearance rate of 60% at 12 months, compared to 33% for the placebo cohort. But the other four groups received either little additional benefit or actually fared worse, with clearance rates ranging from just 11% to 36%.

It was a similar story when it came to clearing cervical lesions. The highest clearance rate of 67% was observed in two of the groups—both of which received the highest dose of ChAdOx—compared to 39% in the placebo cohort. But the other three groups saw rates of just 20%, 33% and 40%.

Ultimately, when the data from all five groups were pooled, they didn’t demonstrate a significant improvement in hrHPV clearance or cervical lesion clearance, the biotech acknowledged.

For now, the company is evaluating “future development options for the VTP-200 program.”

“We were pleased to see that VTP-200 was generally well-tolerated, meeting the primary safety endpoint in this study,” Barinthus Chief Scientific Officer Nadege Pelletier, Ph.D., said in the release.

“The most promising hrHPV and cervical lesion clearance data were observed in the highest ChAdOx-HPV dosing groups which is informative for future development,” Pelletier added. “However, these differences compared to placebo were not statistically significant given that the trial was not powered for individual dose group comparisons.”

“Further analyses are ongoing, mostly focusing on immunological responses and we plan to share the detailed results in due course,” she said.