Sexual & Reproductive Health
Hepatitis B is a disease of the liver caused by infection with the hepatitis B virus (HBV), and can be either acute or chronic. Acute infection is more common and more severe in adults and adolescents, but the likelihood of developing chronic disease is dramatically higher in infants and children under five.
As many as 80-90% of children infected during the first year of life will progress to chronic disease, but this falls to less than 5% for otherwise healthy adults. Almost all of the burden of HBV-related disease is due to chronic hepatitis B – largely due to cirrhosis or liver cancer – following infection transmitted from mother to child at birth or acquired in early infancy. Although HBV is prevalent worldwide, the burden of hepatitis B is disproportionately high in low- and middle-income countries, and co-infection with HIV is not uncommon. Hepatitis B product R&D was added to the G-FINDER scope in the 2019 report, restricted to LMIC use and applicability.
An effective vaccine against HBV exists and has been included in 185 countries’ national infant immunisation schedules. Current nucleos(t)ide analogues are safe, well tolerated and halt transmission; but life-long treatment is needed to avoid relapse. New therapies are aimed at a functional cure – sustained undetectable viraemia with or without antibody production – with multiple drugs and biologic combinations in clinical development. Tools to diagnose and treat HBV remain sub-optimal as standard serological assays detecting HBV surface antigen (HBsAg) are compromised by HIV/HCV co-infection, low HBsAG titres, and S gene mutations/variants. None of the available molecular tests are pre-qualified by WHO, and there is a need for low-cost, point-of-care molecular diagnostics that can quantify viral load, for confirmation of diagnosis, treatment monitoring, detection of drug resistance, and treatment initiation to prevent mother-to-child transmission. Epidemiological research in LMICs is needed to inform approaches to screening, monitoring and treatment, and advance understanding of drug and vaccine escape mutations.
Bepirovirsen, an antisense oligonucleotide that targets HBV mRNA, resulting in cessation of HBsAg production, has entered a Phase III trial after demonstrating potential efficacy in two Phase II studies. If found effective, it would be the first compound to provide a functional cure, offering substantial improvement on the current standard of care. Bepirovirsen is also being investigated as part of combination therapy with GSK3528869A, a viral-vectored immunotherapeutic. A Phase II safety and efficacy study of combination treatment of BRII-835 (VIR-2218), an RNA interference compound, and BRII-179 (VBI-2601), a protein-based HBV immunotherapeutic candidate, in adult participants with chronic HBV infection was completed in July 2023. Interim data suggested the combination induced meaningfully stronger anti-hepatitis B surface antigen (HBsAg)- specific T-cell and antibody responses than BRII-835 alone.