GSK stakes out path to hepatitis B functional cure after clearing virus in phase 2b trial

GSK has taken a step toward its goal of providing a functional cure to hepatitis B patients. After 24 weeks of treatment, almost 30% of participants in a phase 2b clinical trial had undetectable levels of the virus, ramping up expectations ahead of the delivery of data on durability and the start of a pivotal study.

Currently, the hepatitis B treatment toolkit centers on interferon-type molecules and nu­cle­o­side analogs such as entecavir, tenofovir disoproxil fumarate and tenofovir alafenamide. Interferon molecules boost the immune system, and nu­cle­o­side analogs stop or slow replication of the virus. Yet, even when used in combination, only a small percentage of patients have undetectable levels of hepatitis B surface antigen.

GSK, having paid Ionis Pharmaceuticals $25 million upfront in 2019, is one of a set of companies trying to ramp up the percentage of patients with undetectable levels of the antigen. The Big Pharma used the European Association for the Study of the Liver’s International Liver Congress 2022 to showcase its work on the antisense therapy bepirovirsen.

In an interim analysis of the phase 2b B-Clear clinical trial, GSK found undetectable levels of hepatitis B surface antigen and DNA in almost 30% of participants who received 300 mg bepirovirsen for 24 weeks, regardless of whether they were also taking nu­cle­o­side analogs. The figures were 28% in the nu­cle­o­side analog combination arm and 29% in the bepirovirsen single agent cohort. 

The figures suggest bepirovirsen may improve on the standard of care, while leaving room to improve and unanswered questions. The critical question that GSK is still assessing is whether the responses are durable. If responders can come off bepirovirsen and keep the virus in check, GSK may be on course to deliver a functional cure, at least for the minority of patients who respond to the single agent therapy.

How to help the more than 70% of patients who still had detectable levels of hepatitis B is another key question. GSK is looking to combinations to boost the response rate, with midphase trials of bepirovirsen alongside pegylated interferon and targeted immunotherapy on its roster of hepatitis B studies. 

The combination work will advance in parallel to a push to validate the effect of bepirovirsen as a single agent. A phase 3 monotherapy study is set to start in the first half of next year, positioning GSK to show whether it can replicate the phase 2b response rate in a larger trial. GSK sees a 2 billion pound sterling ($2.5 billion)-plus global opportunity for the drug but faces competition from rivals including Johnson & Johnson.