VTP-300, Nivolumab Combination Shows Promise for Functional HBV Cure in Phase 2b Trial

New phase 2b data from the ongoing HBV003 clinical trial demonstrate the ability of VTP-300 combined with low-dose nivolumab to stimulate immune response and induce sustained reductions in hepatitis B surface antigen (HBsAg) meeting functional cure criteria.

The data were presented at The Liver Meeting 2024 from the American Association for the Study of Liver Diseases (AASLD) and included 40 participants with HBsAg < 200 IU/mL at screening who had reached day 169 and were assessed for nucleos(t)ide analogue (NUC) discontinuation. Of these patients, 8 had complete HBsAg loss and 2 met the criteria for functional cure, defined by AASLD as sustained HBsAg loss and hepatitis B virus DNA <LLOQ for 6 months off-treatment.

“Sustained HBsAg loss has proven to be the largest hurdle in getting chronic hepatitis B patients to functional cure,” Chun-Jen Liu, MD, PhD, an investigator on HBV003 and director of the Hepatitis Research Center and Clinical Trial Center at National Taiwan University Hospital, said in a press release. “The data we are seeing with VTP-300 is unique because they indicate a durable loss of HBsAg in participants, including two who met the criteria for functional cure. These data bring us a step closer to potentially allowing some patients with chronic hepatitis B to come off life-long antiviral treatment, remain healthy and don’t progress to liver failure or cancer.”

VTP-300 is an immunotherapeutic candidate consisting of an initial dose using the ChAdOx vector and a secondary dose(s) using the MVA vector, both encoding multiple HBsAg, including full-length surface, modified polymerase, and core antigens. Of note, it is the first antigen-specific immunotherapy that has been shown to induce sustained reductions in HBsAg. Barinthus Bio is studying VTP-300 in combination with other agents, including siRNA and low-dose anti-PD-1 antibodies in the ongoing IM-PROVE II trial.

The HBV003 trial is designed to assess different dosing regimens of VTP-300 in combination with low-dose nivolumab, an anti-PD-1 monoclonal antibody. All groups received ChAdOx on day 1. Groups 1 and 2 received MVA with nivolumab on day 29, and group 2 was dosed again with MVA and nivolumab on day 85. Group 3 received only MVA on day 29, nivolumab on day 36, and a conditional second MVA dose on day 85 to evaluate anti-PD-1 inhibition timing. The conditional MVA dose was administered if participants had HBsAg ≥10 IU/mL.

In 2023, the study inclusion criteria were amended from people with chronic hepatitis B with HBsAg ≥10 and <4,000 IU/mL to ≥10 and ≤200 IU/mL, as the strongest responses were observed in participants with HBsAg ≤200 IU/ml.

The HBV003 study is fully recruited and includes 121 participants, 69 of whom entered the trial with HBsAg levels < 200 IU/mL. Investigators assessed NUC discontinuation in 40 participants with HBsAg < 200 IU/mL at screening who reached day 169.

Of these patients, 24 were eligible for discontinuation and 9 chose to discontinue NUCs. Among 6 patients who remained off NUC therapy, 2 have met the criteria for functional cure and 2 have seroconverted to HBsAb positivity.

Investigators noted durable HBsAg declines were observed in all treatment groups, additionally pointing out VTP-300 in combination with low-dose nivolumab was generally well tolerated with no treatment-related severe adverse events observed or reported.

"These Phase 2 data are incredibly encouraging and demonstrate the ability of VTP-300 to stimulate the immune response and induce sustained reductions in HBsAg to the point of meeting functional cure criteria,” said Nadege Pelletier, PhD, chief scientific officer of Barinthus Bio. "Moreover, the finding that one of the participants meeting functional cure criteria had antibodies against hepatitis B is promising as HBsAb positivity is associated with long-term control of the infection by the immune system.”

Reference

^{Barinthus Bio. Barinthus Bio Announces Results From Ongoing Phase 2b Chronic Hepatitis B Trial, Including Achievement of Functional Cure and HBsAb Seroconversion. November 15, 2024. Accessed November 15, 2024. https://www.globenewswire.com/news-release/2024/11/15/2982138/0/en/Barinthus-Bio-Announces-Results-From-Ongoing-Phase-2b-Chronic-Hepatitis-B-Trial-Including-Achievement-of-Functional-Cure-and-HBsAb-Seroconversion.html}