Investigational Chronic Hepatitis B Drug Could Help Achieve Functional Cure

The landscape of chronic hepatitis B management is facing a potential shift following the publication of positive pivotal data from 2 major phase 3 trials, B-Well 1 (NCT05630807) and B-Well 2 (NCT05630820), in the New England Journal of Medicine.¹

For decades, pharmacists and clinicians have managed chronic hepatitis B (CHB) as a lifelong condition requiring continuous nucleos(t)ide analogue (NA) therapy to suppress viral replication, as functional cure rates with current standards of care remain below one percent. However, new findings for the investigational drug bepirovirsen suggest that a finite 24-week treatment course can achieve a functional cure—defined as sustained undetectable hepatitis B surface antigen (HBsAg) and HBV DNA for at least 6 months after stopping all medication—in approximately 20% of patients.^1-3

“CHB affects over 240 million people worldwide and accounts for over half of global liver cancer cases,” Tony Wood, chief scientific officer at GSK, said in a news release.² “For the first time, bepirovirsen offers the possibility of significantly better functional cure rates than the current standard of care and the potential to reduce the risk of long-term liver complications, including cancer. This is a major step forward in our growing pipeline to treat liver disease to help transform outcomes for patients.”

About B-Well 1 and B-Well 2 Trials

Bepirovirsen represents a novel class of therapy known as an antisense oligonucleotide (ASO). Unlike traditional NAs that primarily inhibit viral replication, bepirovirsen is designed to recognize and inhibit the production of viral genetic components, effectively reducing the levels of HBV DNA and HBsAg in the blood and simultaneously stimulating the patient’s own immune system. This dual mechanism of action aims to help the immune system regain control of the virus, potentially eliminating the need for the lifelong adherence and resistance monitoring associated with current oral antiviral therapies.^1-3

The clinical evidence from the replicate B-Well trials, which enrolled over 1800 noncirrhotic adult patients across 29 countries, demonstrated that the efficacy of bepirovirsen is significantly influenced by a patient's baseline viral activity. Although the overall functional cure rate was roughly 19% to 20%, this figure rose to between 25% and 28% in a key subgroup of patients with lower baseline HBsAg levels of 1000 IU/mL or less.¹

Conversely, patients with higher baseline viral loads (between 1000 and 3000 IU/mL) saw lower functional cure rates, ranging from five to ten percent. For pharmacists, these results underscore the growing importance of quantitative HBsAg testing in identifying which patients are most likely to benefit from this finite therapeutic approach.¹

From a safety and clinical monitoring perspective, the B-Well data provide insights for pharmacy teams regarding the expected adverse event profile of ASO therapy. The most frequently observed adverse events (AEs) were injection site reactions, such as erythema and pain, which occurred in 53% of bepirovirsen recipients and were typically mild in severity. More significantly, 24% of patients experienced increases in alanine aminotransferase (ALT) levels. Although ALT flares can be concerning in liver disease, researchers noted that these transient increases often coincided with rapid decreases in HBsAg levels, suggesting they may serve as a marker of a positive therapeutic immune response rather than drug-induced liver injury.²

Pharmacists should also be aware of the transient hematologic and renal effects observed during the 24-week treatment period. The trials reported temporary decreases in mean platelet counts and estimated glomerular filtration rates, although these levels generally returned to near-baseline values by week 72, which was 48 weeks after completing bepirovirsen therapy. Because 16% of patients in the trials experienced AEs of grade 3 or higher, compared to only 3% in the placebo group, experts emphasize that rigorous adherence to monitoring guidelines and dose-pausing protocols will be essential for the safe implementation of this drug in clinical practice.^1,3

The Role of the Pharmacist

The implications of achieving a functional cure extend beyond the convenience of stopping daily medication, as HBsAg loss is clinically associated with an 89% reduction in the risk of liver cancer and a 62% reduction in all-cause mortality. With chronic hepatitis B currently affecting 240 million people worldwide and causing over one million deaths annually, the potential to transition even a fifth of the patient population to a treatment-free state is a major public health milestone.^2,3

Bepirovirsen has already received fast track and breakthrough therapy designations from the FDA, and regulatory decisions are anticipated as early as the third quarter of 2026. As launch preparations begin, the pharmacy profession will likely play a central role in educating patients on this new therapeutic category and managing the complex monitoring required to achieve these unprecedented cure rates.^2,3

“Today’s standard of care for CHB imposes a heavy burden on patients and health care systems and rarely delivers a functional cure,” Jinlin Hou, MD, chairman and professor of the Hepatology Unit and Department of Infectious Diseases at the Nanfang Hospital in the Southern Medical University, said in the news release.² “With recent guidelines now prioritizing functional cure, these new data could represent an important advance. Combined with improved testing and diagnosis, this innovation has the potential to improve the lives of millions living with CHB.”

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REFERENCES

1. Hou J, Lim SG, Buti M, et al. Phase 3 Results of Bepirovirsen Treatment for Chronic Hepatitis B Virus Infection. N Engl J Med. Published online May 28, 2026. doi:10.1056/NEJMoa2515131

2. Bepirovirsen achieves unprecedented functional cure rates with potential to redefine treatment for chronic hepatitis B. News release. GSK. May 28, 2026. Accessed June 2, 2026. https://www.gsk.com/en-gb/media/press-releases/bepirovirsen-achieves-unprecedented-functional-cure-rates-with-potential-to-redefine-treatment-for-chronic-hepatitis-b/

3. Van Beusekom M. Phase 3 trials of novel drug show functional cure in 20% of chronic hepatitis B patients. News release. University of Minnesota. May 28, 2026. Accessed June 2, 2026. https://www.cidrap.umn.edu/hepatitis/phase-3-trials-novel-drug-show-functional-cure-20-chronic-hepatitis-b-patients