At The Liver Meeting, Barinthus Biotherapeutics (formerly Vaccitech), announced data from a study examining their immunization candidate, VTP-300, used together with Arbutus Biopharma’s investigational HBV therapeutic, imdusiran. Investigators found the combination of imdusiran and VTP-300 demonstrated meaningful reductions of hepatitis B surface antigen (HBsAg) levels that were maintained well below baseline.
“Imdusiran consistently delivers compelling efficacy and safety data in multiple Phase 2a populations and combinations. In this trial, all but 1 patient reached surface antigen levels below 100 IU/mL and one reached <LLOQ (lower limit of quantification) with 24 weeks of imdusiran plus NUC therapy alone, which is a meaningful achievement as we believe lowering surface antigen is key to promoting host HBV-specific immune reawakening,” Arbutus Biopharma Chief Medical Officer Karen Sims, MD, PhD, said in a statement.
VTP-300 consists of an initial dose using the ChAdOx vector and a secondary dose(s) using the MVA-vectored platform, 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.
Imdusiran, which is an RNA interference (RNAi) therapeutic specifically designed to reduce all HBV viral proteins and antigens including hepatitis B surface antigen. This is thought to be a key prerequisite to enable reawakening of a patient’s immune system to respond to the virus. Imdusiran targets hepatocytes using Arbutus’ novel covalently conjugated N-Acetylgalactosamine (GalNAc) delivery technology enabling subcutaneous delivery. Clinical data generated thus far has shown single and multiple doses of imdusiran to be generally safe and well-tolerated, while also providing meaningful reductions in hepatitis B surface antigen and hepatitis B DNA. Imdusiran is currently in multiple Phase 2a clinical trials.
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The combination therapy of imdusiran and VTP-300 demonstrated robust reductions in HBsAg levels during the imdusiran treatment period.
The study showed that the combination therapy maintained meaningful reductions of HBsAg levels well below baseline. Notably, 97% of imdusiran-treated patients had HBsAg levels below 100 IU/mL at the time of the first VTP-300/placebo dose.
VTP-300, described as the first antigen-specific immunotherapy, demonstrated sustained reductions in HBsAg. Moreover, preliminary immunology data suggested enhanced HBV-specific T cell interferon-gamma (IFN-γ) production in patients receiving imdusiran plus VTP-300 compared to the placebo.
Investigators enrolled 40 non-cirrhotic, virally suppressed chronic hepatitis B (CHB) patients that were on stable NUC therapy. The patients initially received imdusiran (60mg every 8 weeks) for 24 weeks and were then randomized to receive either VTP-300 or placebo at week 26 and 30 (and conditionally at week 38 if they experienced a >0.5 log10 decline in HBsAg between Weeks 26 and 34), in addition to ongoing NUC therapy. The preliminary data include a subset of patients that received the 2 dose VTP-300 regimen (28/40 patients) and available follow-up data to Week 48 (12/40 patients) and showed the following:
- Reductions of HBsAg were seen during the imdusiran treatment period (-1.86 log10 mean reduction from baseline after 24 weeks of treatment). This decline in HBsAg is comparable to the declines seen with imdusiran in other clinical trials conducted to date.
- 97% of the imdusiran treated patients (33/34) had HBsAg <100 IU/mL at the time of the first VTP-300/placebo dose.
- VTP-300 treatment appeared to contribute to the maintenance of low HBsAg levels in the early post-treatment period, as the mean HBsAg levels in the placebo group begin to increase starting approximately 12 weeks after the last dose of imdusiran.
- All VTP-300 treated patients have maintained HBsAg <100 IU/mL through week 48, 60% have maintained HBsAg <10 IU/mL, and all have qualified to stop NUC therapy.
- Preliminary immunology data suggests HBV-specific T cell IFN-γ production was enhanced in patients receiving imdusiran plus VTP-300 compared to placebo.
The preliminary safety data from this trial demonstrate that imdusiran and VTP-300 were both generally well-tolerated. There were no serious adverse events, Grade 3 or 4 adverse events or treatment discontinuations.
“As we continue to dose and follow these patients, I look forward to seeing the potential that imdusiran, VTP-300, and NUC therapy can have on achieving a functional cure for patients with CHB,” Sims said in the same statement.
HBV003 Trial and Phase 2a AB-729-202 Trial in Collaboration with Arbutus Biopharma in Chronic HBV Patients at AASLD. Barinthus Biotherapeutics press release. November 9, 2023.