U-M hepatologist hails hepatitis B treatment trial results

In an editorial published in the New England Journal of Medicine, University of Michigan Health hepatologist Anna S. Lok, M.D., hails newly announced results of the B-Well clinical trials as “a major step toward a functional cure for hepatitis B virus infection.”

The results, published concurrently in NEJM, report that 20% and 19% of patients in two duplicate clinical trials achieved a functional cure for their chronic hepatitis B infections following 24 weeks of bepirovirsen (versus 0% of the placebo groups).

The lead and corresponding author of the trial results is Jinlin Hou, M.D., Chairman and Professor of the Hepatology Unit and Department of Infectious Diseases, Southern Medical University in Guangzhou, China.

The University of Michigan Health did not participate in these clinical trials.

The most common treatment for chronic hepatitis B infection, nucleoside or nucleotide analogue (NA) therapy, can successfully suppress hepatitis B virus replication — reducing the risk of cirrhosis and cancer — but is rarely curative, and most patients will relapse if treatment is discontinued before hepatitis B surface antigen loss.

In 2016, Lok led the first meeting among the US Food and Drug Administration, European Medicine Agency, American Association for the Study of Liver Diseases, European Association for the Study of the Liver, and experts in academia and industry to discuss definition and paths towards a cure for hepatitis B.

This group of experts recommended that functional cure of hepatitis B should be defined as undetectable hepatitis B surface antigen and hepatitis B virus DNA at least 24 weeks after completing a finite course of treatment. During the past 10 years, many clinical trials testing different combinations of antiviral and immunomodulatory agents have been evaluated but only one phase 3 trial has been completed so far.  

In these latest phase 3 clinical trials, 24% of the patients taking bepirovirsen were able to discontinue NA therapy, compared to zero patients in the placebo groups, and none of the patients who discontinued NA therapy including a few who failed to achieve functional cure had clinical relapse.

Although these trials were conducted in highly selected patients and the results may not be generalizable to other patients with chronic hepatitis B — and side effects were more common among the patients who received bepirovirsen — they are encouraging and represent a major step towards a cure for hepatitis B. Lok hopes the results of these trials will encourage testing of other combinations that are safe and can lead to higher rates of functional cure in broader patient populations.

A renowned researcher into the natural history and treatment of hepatitis B, Lok co-authored every edition of the American Association for the Study of the Liver Diseases Guidelines on hepatitis B since 2001 and the first World Health Organization guideline on the condition in 2015.

Earlier this month, she was the senior author on a review of the current state of global hepatitis B virus prevention and treatment, published in JAMA.