Will WHO’s new guidance spur hepatitis B immunisation?

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Despite vaccine developments signalling advancements in the diagnosis, prevention and treatment of hepatitis B, the World Health Organization’s (WHO) 2024 Global Hepatitis Report reveals that viral hepatitis is claiming 1.3 million per year. Every day, 3,500 people are dying globally due to hepatitis B (HBV) and C infections. 

New data from 187 countries shows that of these deaths, 83% were caused by hepatitis B. “This report paints a troubling picture: despite progress globally in preventing hepatitis infections, deaths are rising because far too few people with hepatitis are being diagnosed and treated,” said WHO Director-General Dr. Tedros Adhanom Ghebreyesus, in an announcement accompanying the report release.

On 29 March 2024, the WHO released new guidance on preventing, diagnosing and treating chronic HBV, a major health issue affecting nearly 300 million people worldwide, according to a 2020 research study. With the updated HBV guidelines, it’s projected that over 50% of individuals with chronic hepatitis B infections may require treatment based on various factors such as eligibility and setting.

To prevent liver diseases and achieve its target of eliminating HBV by 2030, WHO is urging a wider adoption of viral hepatitis prevention, testing, and treatment.

In 2023, Global Data reported more than 50 companies are developing and utilising HBV peptides derived from HBV, with Compagnie Merieux Alliance, Globeimmune and GSK leading the number of related patents filed between 2010 and 2022.

GlobalData is the parent company of Pharma Technology Focus.

While strides have been made in reducing mother-to-child-transmission (MTCT) of HBV through universal infant immunisation, HBV birth-dose coverage remains at less than half (45%) worldwide. 

The HBV vaccine’s effectiveness can therefore be measured in two ways, a 2024 study states: its ability to induce protective antibodies (anti-HBs) and its success in preventing MTCTs (Al-Busafi et al; Vaccines (Basel). 2024 Mar; 12(3): 288). The WHO Hepatitis report states that completing the infant HBV vaccine series results in immune protection and infection prevention for more than 95% of children. 

While coverage of the three-dose HBV vaccine for infants met its 2030 goal of 90% in 2020, increasing from 82% in 2015, MTCT did not follow the same positive trajectory. Although coverage has increased from 38% in 2015 to 50% in 2020, it is still far from its goal of reaching 90% by 2030. 

The WHO’s 2024 hepatitis B treatment and prevention guidelines highlight the need for coverage of HBsAg testing of pregnant women to reach 90% or more of the globe by 2030. The WHO states that where neither HBV DNA nor HBeAg testing is available, prophylaxis with tenofovir disoproxil fumarate (TDF) is recommended for all HBV-positive (HBsAg-positive) pregnant women to prevent the MTCT of HBV.

While widespread, only around 10% of these people have a chronic HBV diagnosis and only 5% receive treatment, research has found (Lancet Gastroenterol Hepatol, 2018 Jun;3(6):383-403). Current treatment options offer less than a 2 – 8% functional cure rate, research indicates, which is not considered clinically meaningful (Leen Slaets, GastroHep, doi.org/10.1002/ygh2.393). 

HBV infection acquired in adulthood leads to chronic hepatitis B in less than 5% of cases. However, infection in infancy and early childhood leads to chronic hepatitis B in about 95% of cases, the WHO reports. Universal infant immunisation, including birth dose vaccination, is most effective in preventing chronic hepatitis B (Jeng et al; The Lancet, Volume 401, Issue 10381, p1039-1052, March 25, 2023). Therefore, the healthcare industry advocates to strengthen and prioritise infant and childhood vaccination.

Scientists in a The Lancet study found that improving vaccination coverage and developing curative therapies are among the actions required to meet the WHO’s goal of eliminating HBV by 2030.

In 2023, Korea’s LG Chem secured a $200m deal in 2023 with the United Nations Children’s Fund (UNICEF) to supply its pentavalent vaccine, Eupenta, which protects against HBV.

Pharmaceutical developments in the past 12 months largely centre around treating chronic hepatitis B. In February 2024, GSK announced the US Food and Drug Administration (FDA) gave fast track designation for bepirovirsen, an investigational antisense oligonucleotide (ASO), to treat chronic hepatitis B. GSK is undertaking a Phase III programme, B-Well, and has published data from the Phase IIb trials B-Clear and B-Sure, which assess the efficacy, safety and durability of bepirovirsen response in chronic hepatitis B patients. 

In December 2023, Belgium’s AstriVax was awarded $3.3m (€3m) to develop a therapeutic vaccine for HBV. Awarded by Flanders Innovation & Entrepreneurship (VLAIO), the government grant will be used to accelerate the company’s therapeutic vaccine targeting chronic hepatitis B. “This therapeutic vaccination strategy may play a key role in the steps towards functional cure for those patients that suffer from a chronic Hepatitis infection,” said Dr. Hanne Callewaert, CEO of AstriVax. 

Aligos Therapeutics, another biotech, announced HBV data with its drug ALG-000184 in November 2023. At the time, Dr. Lawrence Blatt, the company’s chairman and CEO said: “ALG-000184 is the first CHB drug to affect cDNA antigen expression levels via two mechanisms of action and may play a central role in future efforts to achieve higher rates of chronic DNA suppression or functional cure.” 

After BlueJay Therapeutics raised $41m in 2022 to drive clinical trials in chronic hepatitis B, the biopharmaceutical company announced this year that the European Medicines Agency (EMA) has granted Priority Medicine (PRIME) designation to BJT-778 to treat chronic Hepatitis Delta Virus (HDV) infection. The company is developing BJT-778, a human IgG1 monoclonal antibody against HBV surface antigen for both chronic HBV and HDV. The launch of the HEPLISAV-B vaccine in 2023 signalled the first and only adult HBV vaccine approved in the US, the European Union (EU) and UK to enable HBV immunisation.