GSK’s six-monthly triple-action investigational antisense oligonucleotide (ASO) candidate has demonstrated a clinically and statistically significant functional cure in chronic hepatitis B in two Phase III trials.
The B-Well 1 (NCT05630807) and B-Well 2 (NCT05630820) studies, which enrolled over 1,800 patients from 29 countries, met their primary endpoint, and bepirovirsen demonstrated a statistically significant and clinically meaningful functional cure rate.
Functional cure rates were significantly higher with bepirovirsen plus standard of care (SoC) compared with SoC alone.
All ranked endpoints were statistically significant, including in patients with baseline surface antigen (HBsAg) <=1000 IU/ml where an even greater effect was demonstrated. The drug also proved to be safe and tolerable in the trials.
Based on the Phase III trials, GSK will be filing for regulatory approval of the drug globally. Full data will be presented at an upcoming medical meeting.
Tony Wood, chief scientific officer, GSK, said: “Bepirovirsen has the potential to transform treatment goals for people living with CHB by achieving significant functional cure rates – a first for the disease. CHB affects more than 250 million people and leads to approximately 56% of liver cancer cases worldwide. Today’s result supports our plans to progress bepirovirsen as a treatment and also continue its development as a backbone in future sequential therapies.”
Current SoC for hepatitis B is nucleoside and nucleotide analogues, which often require lifelong therapy and the functional cure rates remain low, typically only 1%.
Bepirovirsen acts by inhibiting the replication of viral DNA in the body, suppressing the level of hepatitis B surface antigen (HBsAg) in the blood, and stimulating the immune system to increase the chances of a durable and sustained response.
GSK licensed the drug from Ionis in 2019, following a positive Phase II trial, and collaborated with the company on its development.
The drug gained Fast Track designation from the US Food and Drug Administration (FDA), Breakthrough Therapy designation from the Chinese National Medical Products Administration (NMPA) and SENKU designation from the Japanese Pharmaceuticals and Medical Devices Agency (PMDA).
GlobalData predicts the hepatitis B therapeutics market to reach $3.2bn across seven major markets (7MM: the US, France, Germany, Italy, Spain, the UK, and Japan) in 2034. By this year, more than 65% of the market will be attributed to sales from specific functional cure drugs.
As well as bepirovirsen, GlobalData also believes that a host of rival drugs will launch before 2034. This includes Gilead Sciences’ toll-like receptor 8 (TLR8) agonist, selgantolimod; GSK’s small interfering ribonucleic acid, daplusiran plus tomligisiran; Aligos Therapeutics’ capsid protein inhibitor, ALG-000184; and Arbutus Biopharma’s hepatitis B virus (HBV) surface antigen inhibitor, imdusiran.
Stephanie Kurdach, infectious disease analyst at GlobalData, said: “Functional cure drugs are projected to be more expensive than the currently marketed chronic hepatitis B therapeutics, thereby driving the growth of the market. By 2034, the forecasted functional cure drugs will account for over 65% of the chronic hepatitis B market sales.”
GlobalData is the parent company of Clinical Trials Arena.
