Encouraging HBV Vaccine Data Presented at Liver Conference

Hepatitis B

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This article first appeared on ContagionLive.com.

At the ongoing EASL Congress 2023, Vaccitech plans to present a poster with data about its investigational hepatitis B vaccine, VTP-300. Specifically, the data will come from the company’s phase 1b/2a clinical trial studying the vaccine in adults with chronic hepatitis B (CHB).

According to Vaccitech, 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 8 months after the 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 8 months post-final dose.

“The durable reductions in HBsAg we saw in this study are exciting because they support the idea that VTP-300 could be a critical component to enhancing rates of functional cure for people with chronic Hepatitis B,” Vaccitech’s Chief Medical OfficerMeg Marshall, MD, said in a statement.

The company is involved in discovering and developing novel immunotherapeutics for treating autoimmunity, chronic infectious diseases, and cancer.

Trial 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 4 groups to receive VTP-300 and low-dose nivolumab combinations, with follow-up for 8 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, 2 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 2 months post-final dose, with durable responses continuing 8 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 a relation was 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 8 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 8 months after the 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 2 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 announced in June 2022.

The Vaccine and Ongoing Trial Plans
VTP-300 is an immunotherapeutic vaccine 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 shown to induce sustained reductions in HBsAg.

The company has 2 trials in the works. A phase 2b clinical trial (HBV003; NCT05343481) to evaluate the timing of the low dose nivolumab, additional doses of the MVA component of VTP-300 and a nucleos(t)ide analogues discontinuation protocol, has been initiated in multiple countries across the Asia-Pacific region, with over 40% of the 120 participants enrolled to date (40 per group) and interim data expected in Q4 2023.

They also have a phase 2a clinical trial, in collaboration with Arbutus Biopharma Corporation, which is evaluating the safety, antiviral activity, and T cell responses of VTP-300 administered after Arbutus’ AB-729 in 40 virologically-suppressed people with chronic HBV infection, with interim data expected in Q4 2023.