Barinthus Biotherapeutics has announced promising data from its ongoing Phase IIb HBV003 clinical trial evaluating VTP-300 for chronic hepatitis B. The data, which were cut off on September 30 for lab results and October 8 for clinical findings, reveal that VTP-300, in combination with a low dose of nivolumab, led to complete hepatitis B surface antigen (HBsAg) loss in eight patients. This outcome offers a potential advancement in the treatment of chronic hepatitis B, a condition affecting over 250 million people worldwide.
Key Findings from the HBV003 Trial
The HBV003 trial, which includes 121 patients, focuses on those with HBsAg levels below 200IU/mL at screening. According to the latest data, eight patients achieved complete HBsAg loss, defined as HBsAg levels below the lower limit of quantitation (<0.05IU/mL). Notably, two of these patients met the criteria for functional cure, demonstrating sustained HBsAg loss and hepatitis B virus DNA <LLOQ for six months off-treatment.
Furthermore, two of the eight patients who experienced HBsAg loss developed anti-hepatitis B antibodies (HBsAb) that were not present before, including one of the individuals who met the functional cure criteria. These results suggest a potential for durable responses in patients treated with VTP-300 and low-dose nivolumab.
NUC Discontinuation and Durable Responses
The trial also assessed nucleos(t)ide analogue (NUC) discontinuation in 40 patients with HBsAg below 200IU/mL at screening who had reached day 169 of the trial. Of these, 24 were eligible for NUC discontinuation, including the eight patients who achieved HBsAg loss. Nine patients chose to discontinue NUCs, and six remained off NUC therapy, with five maintaining this status for over six months. Among these six, two met the criteria for functional cure, and two seroconverted to HBsAb positivity.
The data, to be presented at the American Association for the Study of Liver Diseases (AASLD) 2024 liver meeting by Dr. Chun-Jen Li, also demonstrated durable HBsAg declines across all treatment groups, consistent with data presented at the European Association for the Study of the Liver (EASL) Congress in June 2024.
Safety and Tolerability
Preliminary safety data indicate that VTP-300 in combination with low-dose nivolumab was generally well tolerated. As of the data cut-off, no treatment-related serious adverse events had been observed or reported.
Expert Commentary
Dr. Liu commented, "Sustained HBsAg loss has proven to be the largest hurdle in getting chronic hepatitis B patients to functional cure. 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. Although the study is still ongoing, these early data may bring us a step closer to potentially allowing some patients with chronic hepatitis B to come off antiviral treatment without their chronic hepatitis B progressing."
Global Impact of Chronic Hepatitis B
According to the World Health Organization (WHO), over 250 million people worldwide have chronic hepatitis B. New WHO guidelines aim to reduce new infections by 90% and deaths by 65% by 2030. GlobalData epidemiologists project that diagnosed prevalent cases of hepatitis B in 16 major markets will rise from 21,499,000 in 2024 to 22,430,000 in 2029.
