VTP-300 Ganavolumab reduces HBsAG, showing potential in HBV treatment options

The investigational novel antigen-specific immunotherapy VTP-300, in combination with nivolumab, significantly reduced hepatitis B virus (HBV) surface infection in patients with hepatitis B virus (HBV) in approximately 4 months, according to new interim Phase 2b study data. Antigen (HBsAg).

In a study presented this weekend at the American Association for the Study of Liver Diseases (AASLD) 2023 Liver Meeting in Boston, researchers sponsored by Barinthus Biotherapeutics reported findings showing that the combination of VTP-300 and nivolumab gave 13 patients (23%) Trial participants achieved >0.5 log reduction in HBsAg per IU/mL from baseline at Day 113. Ongoing data also show a more significant benefit from the study regimen in patients with baseline HBsAg levels ≤200 IU/mL during this period.

While the researchers continue their late-stage investigations, they note that the data presented at AASLD 2023 shed light on VTP-300’s potential role in functionally curing HBV.

Interim study results presented by study author Dereck Tait, MBChB, consultant at Barinthus, highlight safety and efficacy findings from the ongoing Phase 2b trial of HBV003. Tait also reviewed phase 1b/2a trial data submitted earlier this year, which showed that monotherapy VTP-300 and VTP-300 plus low-dose nivolumab were associated with significant and durable reductions in HBsAg in patients with HBV.

More importantly, previous trials showed that 2 patients (40%) in a cohort of patients with baseline HBsAg levels <100 IU/mL had undetectable HBsAg levels between 3 and 9 months.

“Current treatments for chronic hepatitis B virus infection are effective in reducing liver disease progression, but functional cure is uncommon,” Tate said. “VTP-300 is being studied as a potential component of functional healing therapies.”

VTP-300 is a combination platform of ChAdOx and MVA vector vaccines designed to stimulate the host immune system. It features an antigen based on consensus genotype C, with a full-length surface, modified polymerase and core. Patients received ChAdOx1-HBV on day 1 and then MVA-HBV plus low-dose nivolumab on day 29.

In a phase 2b trial, Tait and colleagues looked at this dose (cohort 1, n = 40) compared with 2 other treatment arms: one additionally received MVA-HBV plus low-dose nivolumab on day 85 ( Group 2, n = 40), and the other received low-dose nivolumab on day 36 instead of day 29, followed by MVA-HBV on day 85 (group 3, n = 40).

The team is recruiting patients from 12 sites in Thailand, Hong Kong, and Taiwan starting in October 2022; only 74 participants were randomized last month, with data available for 56 (76%) participants at the AASLD 2023 presentation Available. Inclusion criteria were HBV DNA ≤1000 IU/mL, HBsAg ≥10 to <4000 IU/mL, and nucleotide analogue (NUC) treatment regimen for ≥6 months.

The primary endpoint sought by the researchers was the percentage of participants with >1 log reduction at 6 months after treatment initiation. Secondary endpoints considered treatment safety and reactogenicity as well as T-cell responses.

The mean patient age at baseline across the 3 treatment groups was 49.7 years. Three-quarters (73%) of patients were male, and the median HBsAg level was 490 IU/mL; 31% had baseline levels ≤200 IU/mL. An additional 22% of patients were HBeAg positive at baseline.

Of the 46 participants with HBsAg log change data up to day 169, 14 belonged to group 1, 16 to group 2, and 16 to group 3.

Tait reported that VTP-300 plus low-dose nivolumab was associated with sustained reductions in HBsAg through day 113; particularly in the cohort with baseline levels ≤200 IU/mL, the combination therapy achieved significant improvements. The majority (54%) of such patients reported a >0.5-log decline from day one, and one-third (31%) reported a >1-log decline.

Overall, 13 (23%) patients reported >0.5 log reduction in HBsAg at day 113, and 5 (9%) reported >1 log reduction.

Regarding safety results, the researchers observed no disruption in the interim data. One serious adverse event, urinary tract infection, was deemed unrelated to the trial. Discontinuation of treatment due to Bell’s palsy was observed in patients who did not receive MVA-HBV on day 85; patients resolved their condition.

Tait also highlighted interim data from a separate ongoing trial showing that VTP-300 combined with imdusiran can provide similar maintenance of reductions in HBsAg levels in patients over 24 weeks. He summarized an update from the Phase 2b trial, noting that VTP-300 plus nivolumab led to a decrease in HBsAg in all treatment groups, particularly in patients with lower baseline levels, over 113 days.

“We believe these early data are encouraging and, combined with interim data from the ongoing imdusiran/VTP-300 study, suggest that VTP-300 may be an important component of functional core therapies in the future,” he said.

refer to

^{Tate D et al. A Phase 2b open-label study designed to evaluate the efficacy, safety, tolerability, immunogenicity and treatment regimen of VTP-300 combined with low-dose Nivolumab in the treatment of chronic hepatitis B infection. Paper presented at: Liver Conference. Boston, MA. November 10-14, 2023.}