Vaccitech is using a novel approach to address the virus and create a functional cure.
Hepatitis B (HBV) is a liver infection that for some patients are sick for a short period of time and recover; however, some people progress to a serious, chronic disease state. Treatment for this latter subset of patients can include antivirals, interferon injections, and when it continues to progress to serious liver damage and cirrhosis, a liver transplant may be required.
Vaccitech is a biotechnology company based in the United Kingdom that has developed an immunotherapy platform to address various infectious diseases including HBV. Specifically, the company’s VTP-300 is an immunotherapeutic candidate consisting of an initial dose using the ChAdOx platform and a secondary dose(s) using MVA, both encoding multiple hepatitis B antigens, including full-length surface, modified polymerase and core antigens. VTP-300 is the first antigen-specific immunotherapy that has been shown to induce sustained reductions in HBsAg.
The company has said it is looking to achieve a functional cure with VTP-300. “Functional cure is a term that has been associated for chronic hepatitis B, with the definition that absence of HBV DNA, absence of HBs antigen circulating, and all of that in the absence of treatment,” Vaccitech Chief Scientific Officer Nadege Pelletier, PhD, said. “So what that means really is that the immune system is now capable of controlling the disease on its own without any outside treatment.”
Trial Data
At the EASL Congress 2023 earlier this year, Vaccitech presented data on VTP-300. Specifically, the data came from the company’s phase 1b/2a clinical trial studying the vaccine in adults with chronic hepatitis B (CHB).
“We were quite excited by those results,” Pelletier said.
According to the company, topline line data demonstrated there were meaningful, durable reductions of hepatitis B Surface Antigen (HBsAg) in all participants with a >0.5 log10 reduction in HBsAg who received VTP-300 alone (Group 2) or in combination with a single administration of low-dose PD-1 inhibitor, nivolumab (Group 3). Two of 5 patients with baseline HBsAg below 100 IU/mL in Group 3, developed a non-detectable HBsAg level, which continued eight months after last dose. Reductions in HBsAg were most prominent in those with lower baseline HBsAg. All participants who received VTP-300 and experienced a >0.5 log10 reduction in HBsAg had durable responses with reductions in HBsAg persisting through to the last measurement eight months post-final dose.
Study Specifics
The trial, HBV002, was an open-label phase 1b/2 study to evaluate the safety, tolerability and immunology readout (T cell responses) of VTP-300, with or without low-dose nivolumab, in people with CHB who are virally suppressed with oral anti-viral therapies. In the HBV002 study, 55 participants were randomized into four groups to receive combinations of VTP-300 and low-dose nivolumab, with follow-up for eight months post-final dose.
VTP-300 as monotherapy and in combination with low-dose nivolumab was administered with no treatment-related serious adverse events. As reported previously, two out of 55 participants experienced transaminase flares. Both incidents occurred in participants with HBsAg declines, but not in any of the participants who cleared HBsAg (<0.05 IU/mL).
Group 2
Meaningful, durable reductions of HBsAg were seen in Group 2 (receiving VTP-300 monotherapy, N=18). Three participants had 0.7, 0.7, and 1.4 log10 declines two months post-final dose, with durable responses continuing eight months post-final dose. These participants all had baseline HBsAg <50 IU/mL.
A robust T cell response was generated and was highest in this group and there was a relation demonstrated between ELISpot response and HBsAg decline.
Group 3
Those in Group 3 received VTP-300 followed by a single low dose of nivolumab together with Modified Vaccinia Ankara (MVA)-HBV (N=18). Two months post-final dose, the mean reduction in HBsAg was 0.76 log10 (p<0.001). This effect persisted with a mean decline of 0.98 log10 at eight months (p<0.001) after the last dose and was most prominent with starting values HBsAg <1,000 IU/mL. Two participants developed non-detectable HBsAg levels, which continued eight months after last dose.
Pre-genomic RNA levels fell significantly in the majority of participants in this group only, consistent with the decline in HBsAg levels.
Groups 1 and 4
No meaningful reductions in HBsAg were observed in Group 1, in which participants received two doses of MVA-HBV without ChAdOx1-HBV, or in Group 4, in which participants received low-dose nivolumab with both doses of VTP-300. These groups were discontinued following interim analysis, as previously announced in June 2022.
In terms of safety, VTP-300 has not demonstrated any issues. “It was very well tolerated, and we didn't have any treatment related severe adverse events,” Pelletier said.
Contagion spoke to Pelletier about developing products for a functional HBV cure, as well as data on VTP-300 and the timetable for reporting future data.
