HBV vaccine demonstrates encouraging results in early clinical trials

A treatment regimen of low dose VBI-2601 (BRII-179) injections in patients with chronic hepatitis B exhibited positive safety, tolerability and efficacy, according to a poster presented at the International Liver Congress.

“Without a functional cure for HBV infection, many of the 290 million people around the world infected with HBV will go on to develop significant and life-threatening complications from the disease such as liver decompensation and hepatocellular carcinoma,” Man-Fun Yuen, DSc, MD, PhD, professor at the University of Hong Kong and study presenter, said in a press release. “These promising human proof-of-mechanism data reinforce the potential for BRII-179 (VBI-2601) to be a critical component in the development of a functional cure for chronic HBV, which could help patients and health care providers manage the effects of this devastating disease and greatly curb disease progression.”

In the randomized, open-label, controlled phase 1b/2a study, Yuen and colleagues evaluated the safety, antiviral activity and immunogenicity of VBI-2601 (BRII-179; VBI Vaccines Inc.), which is composed of the three HBV surface envelope proteins (Pre-S1, Pre-S2 and S). The study involved two parts with different dosing levels, 25 patients testing a 20 mg dose and 24 patients testing 40 mg. The researchers administered four monthly intramuscular injections of BRII-179 (VBI-2601) with or without a multidose IFN-apha Q4W. They recorded antibody and cellular responses to surface antigens and changes with circulating hepatitis B surface antigens over 24 weeks.

Both doses of the injection with or without IFN-alpha were safe and well tolerated in patients. They experienced no severe adverse events. However, common but less serious adverse events included fatigue, injection site reaction, headache, pyrexia or myalgia. Myalgia, pyrexia and flu-like symptoms occurred more often in patients receiving BRII-179 (VBI-2601) with 3MIU IFN-alpha compared with those receiving only BRII-179 (VBI-2601).

Yuen and colleagues recorded significantly higher levels of HBV antigen specific T cell responses against all three peptide pools of the injection at week 16 compared with baseline. Also, most patients responded to at least one of the peptide pools after vaccination (overall 77% at week 16 and 76% at week 20) with IFN-gamma producing T cells improved or restored. BRII-179 (VBI-2601) stimulated anti-HBs antibody response in more than 30% of patients.

“We are encouraged by the results of this study, which provide target engagement and validation, and further support for continuing the clinical development of BRII-179 (VBI-2601),” Li Yan, PhD, chief medical officer of Brii Bio and study author, said in the release. “We look forward to progressing this potentially important immunotherapeutic candidate through our ongoing phase 2 study in combination with BRII-835 (VIR-2218), an investigational small interfering ribonucleic acid targeting HBV, alongside licensing partners, VBI Vaccines and Vir Biotechnology, to deliver a functional cure to patients around the world with chronic HBV, including in China, where there are more than 76 million people living with this devastating disease.”