VTP-300 Plus Nivolumab Lowers HBsAG, Shows Potential for HBV Cure Regimen

Dereck Tait, MBChB

Credit: AME

Investigative novel antigen-specific immunotherapy VTP-300 in combination with nivolumab was associated with significant hepatitis B surface antigen (HBsAg) reduction in patients with hepatitis B virus (HBV) through approximately 4 months, according to new interim phase 2b study data.

In research presented at The Liver Meeting 2023 from the American Association for the Study of Liver Diseases (AASLD) in Boston this weekend, investigators sponsored by Barinthus Biotherapeutics reported findings showing combination VTP-300 plus nivolumab resulted in 13 (23%) trial participants achieving a >0.5 log reduction in HBsAg at day 113 from baseline, per IU/mL. The ongoing data also showed a more significant benefit with the investigative regimen for patients with baseline HBsAg levels ≤200 IU/mL over that time.

While investigators continue the later-stage research, they noted that the data presented at AASLD 2023 elucidate a potential role in functionally curing HBV with VTP-300.

The interim findings presented by study author Dereck Tait, MBChB, a consultant with Barinthus, highlighted safety and efficacy findings from the ongoing HBV003 phase 2b trial. Tait additionally reviewed phase 1b/2a trial data, presented earlier this year, that which showed both monotherapy VTP-300 and VTP-300 plus low-dose nivolumab was associated with significant and durable HBsAg reductions in patients with HBV.

What’s more, the prior trial showed non-detectable HBsAg levels from months 3 - 9 in 2 patients (40%) from a cohort of patients with baseline HBsAg levels <100 IU/mL.

“Current therapies for chronic HBV infection are effective in reducing the progression of liver disease, but functional cure is not common,” Tait said. “VTP-300 is being investigated as a potential component of a functional cure therapy.”

A combination ChAdOx and MVA-vectored vaccine platform, VTP-300 is designed to stimulate the host immune system. IT features antigens based on a consensus genotype C with full-length surface, modified polymerase, and core. Patients are dosed with ChAdOx1 - HBV at day 1, then MVA-HBV plus low-dose nivolumab at day 29.

In the phase 2b trial, Tait and colleagues observed this dose (Group 1, n = 40) versus 2 other treatment arms: one which additionally received MVA-HBV plus low-dose nivolumab at day 85 (Group 2, n = 40), and the other which received low-dose nivolumab at day 36 instead of day 29, then MVA-HBV at day 85 (Group 3, n = 40).

The team enrolled patients from 12 sites in Thailand, Hong Kong and Taiwan beginning October 2022; just 74 participants were randomized by last month, and data were available for 56 (76%) participants at the AASLD 2023 presentation. Criteria for inclusion were HBV DNA ≤1000 IU/mL, HBsAg ≥10 to <4000 IU/mL, and a nucleotide analog (NUC) regimen for ≥6 months.

Investigators sought a primary endpoint of percent of participants with >1 log reduction at 6 months post-treatment initiation. Secondary endpoints regarded treatment safety and reactogenicity, as well as T cell response.

Mean patient age was 49.7 years old across the 3 treatment arms at baseline. Three-fourths (73%) of patients were male, with median HBsAg levels of 490 IU/mL; 31% of patients had levels of ≤200 IU/mL at baseline. Another 22% of patients were HBeAg positive at baseline.

Among the 46 participants with HBsAg log change data through day 169, 14 were in Group 1, 16 were in Group 2, and 16 were in Group 3.

Tait reported that VTP-300 plus low-dose nivolumab was linked to sustained reductions in HBsAg through day 113; particularly among the cohort with ≤200 IU/mL levels at baseline, the combination treatment yielded significant improvement. A majority (54%) of such patients reported >0.5 log decline from day 1, and one-third (31%) reported >1 log decline as well.

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

Regarding safety outcomes, investigators observed no discontinuations in the interim data. One serious adverse event, a urinary tract infection—was deemed unrelated to the trial. A treatment discontinuation due to Bell’s Palsy was observed in a patient who did not receive day 85 MVA-HBV; the patient resolve their condition.

Tait additionally highlighted interim data from a separate, ongoing trial showing combination VTP-300 plus imdusiran may provide similar maintenance of lowered HBsAg levels in patients over 24 weeks. He concluded the update of the phase 2b trial noting that VTP-300 plus nivolumab led to HBsAg declines in all treatment groups, especially patients with lower baseline levels, through 113 days.

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

Reference

^{Tait D, et al. A PHASE 2b, OPEN-LABEL STUDY TO EVALUATE THE EFFICACY, SAFETY, TOLERABILITY, IMMUNOGENICITY AND TREATMENT REGIMENS OF VTP-300 COMBINED WITH LOW-DOSE NIVOLUMAB IN CHRONIC HEPATITIS B INFECTION. Paper presented at: The Liver Meeting. Boston, MA. November 10 - 14, 2023.}