3 key points
- Phase 1b/2a clinical trial data show significant and durable reductions in hepatitis B surface antigen (HBsAg).
- Vaccitech aims to achieve a “functional cure” for chronic hepatitis B with its investigational immunotherapy candidate VTP-300.
- VTP-300 was well tolerated, with no treatment-related serious adverse events reported.
Hepatitis B (HBV) is a liver infection in which some patients develop the disease within a short period of time and recover; however, some develop a severe, chronic disease state. Treatment for the latter group of patients can include antiviral drugs, interferon injections, and, when they go on to develop severe liver damage and cirrhosis, a liver transplant.
Vaccitech is a UK-based biotechnology company developing an immunotherapy platform to treat various infectious diseases, including the hepatitis B virus. Specifically, the company’s VTP-300 is an immunotherapy candidate consisting of an initial dose using the ChAdOx platform and a secondary dose using MVA, both of which encode multiple hepatitis B antigens, including full-length surface antigens , modified polymerase and core antigen. VTP-300 is the first antigen-specific immunotherapy that has been shown to induce sustained reductions in HBsAg.
The company said it is seeking to use VTP-300 to achieve functional cures. “Functional cure is a term associated with chronic hepatitis B and is defined as the absence of HBV DNA, the absence of circulating HBs antigens, and all of these without the need for treatment,” said Nadege Pelletier, Ph.D., chief scientific officer at Vaccitech. “So what this really means is that the immune system is now able to control the disease on its own, without any external treatment.”
Vaccitech demonstrated data for the VTP-300 at the 2023 EASL Conference earlier this year. Specifically, the data comes from the company’s Phase 1b/2a clinical trial, which studied the vaccine’s effects in adults with chronic hepatitis B (CHB).
“We are very excited about these results,” Pelletier said.
According to the company, primary data showed that hepatitis B surface antigen (HBsAg) was reduced by >0.5 log10 in all participants who received VTP-300 alone (Cohort 2) or in combination with a single dose. Meaningful, durable reductions occurred with the low-dose PD-1 inhibitor nivolumab (group 3). Two of the five patients in Group 3 with baseline HBsAg less than 100 IU/mL developed undetectable HBsAg levels that persisted 8 months after the last dose. The reduction in HBsAg was most pronounced among those with low baseline HBsAg. All participants who received VTP-300 and achieved a >0.5 log10 reduction in HBsAg had a durable response, with HBsAg reduction lasting until the last measurement 8 months after the final dose.
The HBV002 trial is an open-label Phase 1b/2 study designed to evaluate the safety, tolerability and immunity of VTP-300, with or without low-dose nivolumab, in virally suppressed patients with chronic hepatitis B. Readings (T cell responses) with oral antiviral therapy. In the HBV002 study, 55 participants were randomized into four groups to receive a combination of VTP-300 and low-dose nivolumab and were followed for eight months after the final dose.
There were no treatment-related serious adverse events with VTP-300 as monotherapy and in combination with low-dose nivolumab. As previously reported, two of the 55 participants experienced elevated transaminases. Both events occurred in participants with HBsAg decline but not in any participants with HBsAg clearance (<0.05 IU/mL).
Significant and durable reductions in HBsAg were observed in Group 2 (receiving VTP-300 monotherapy, N=18). Three participants had log10 decreases of 0.7, 0.7, and 1.4 two months after the final dose, respectively, with durable responses lasting eight months after the final dose. These participants all had baseline HBsAg <50 IU/mL.
A strong T cell response was generated and was the highest in this group, and there was a correlation between ELISpot response and HBsAg decline.
Patients in Arm 3 received VTP-300 followed by a single dose of low-dose nivolumab plus modified vaccinia Ankara (MVA)-HBV (N=18). Two months after the final dose, the mean reduction in HBsAg was 0.76 log10 (p<0.001). This effect persisted eight months after the last dose, with a mean decrease of 0.98 log10 (p<0.001), and was most significant at starting HBsAg values <1,000 IU/mL. Two participants developed undetectable HBsAg levels that persisted eight months after the last dose.
Pregenomic RNA levels decreased significantly in most participants in this group only, consistent with the decrease in HBsAg levels.
Group 1 and Group 4
No significant HBsAg changes were observed in Group 1 (participants received two doses of MVA-HBV without ChAdOx1-HBV) or Group 4 (participants received low-dose nivolumab and two doses of VTP-300). decrease. As previously announced in June 2022, these groups have been discontinued following interim analyses.
In terms of safety, the VTP-300 has not shown any issues yet. “It was very well tolerated and we didn’t have any serious adverse events related to treatment,” Pelletier said.
infect The development of a functional HBV cure product was discussed with Pelletier, as well as data on VTP-300 and a timeline for reporting future data.