GSK (GSK) Study update summary

Disease background and unmet need

• Chronic hepatitis B is a lifelong infection affecting over 240 million people globally, with only 27% diagnosed and less than 5% treated, leading to high mortality and risk of liver cancer.

• Current standard of care (nucleos(t)ide analogues) suppresses HBV DNA but rarely achieves functional cure and requires lifelong therapy.

• Functional cure, defined as sustained loss of hepatitis B surface antigen and HBV DNA suppression after finite therapy, is the new treatment goal and is associated with reduced risk of hepatocellular carcinoma and mortality.

• Major markets include the U.S., China, and Japan, with significant undertreatment and government incentives for improved therapies.

Study design and patient population

• B-Well 1 and 2 were global, replicate, randomized, double-blind, placebo-controlled phase III trials in virologically suppressed chronic hepatitis B patients on stable nucleos(t)ide analogue therapy.

• Patients had HBsAg between 100–3,000 IU/mL, no cirrhosis, and baseline characteristics were balanced across arms.

• Randomization was 2:1 to bepirovirsen or placebo, with 24 weeks of treatment and follow-up for functional cure at week 72.

• Functional cure required stopping nucleos(t)ide analogues after meeting strict virologic and biochemical criteria.

Efficacy results

• Functional cure was achieved in 19% of bepirovirsen-treated patients with baseline HBsAg ≤3,000 IU/mL and 26% with HBsAg ≤1,000 IU/mL; 0% in placebo (p<0.001).

• Sustained HBV DNA suppression off all therapy at week 72 was seen in 23% (≤3,000 IU/mL) and 31% (≤1,000 IU/mL) of bepirovirsen recipients, 0% with placebo.

• An additional 30% of patients achieved HBsAg ≤100 IU/mL, a threshold now recognized as partial cure and clinically meaningful.

• Efficacy was consistent across regions and patient subgroups.