News: Functional cure for Hepatitis B is ‘achievable,’ a new study found

The antisense oligonucleotide bepirovirsen targeting hepatitis B virus (HBV) transcripts indicate a potential functional cure—at least in the short term—according to phase three results from the twin B-Well 1 and B-Well 2 trials that were recently reported in The New England Journal of Medicine.

Adult patients with document HBV infection and without cirrhosis were recruited to B-Well 1 and B-Well 2. In a pooled analysis at 72 weeks, adverse events were reported in 91% of bepirovirsen groups and in 73% of the placebo groups. During the treatment period, adverse events of grade three or higher were reported in 16% on bepirovirsen versus three percent on placebo. Elevated alanine aminotransferase (ALT) was the most common grade three adverse event in the treatment group, affecting 6%.

One in five patients on the drug achieved a functional cure at week 72 after therapy discontinuation, compared with zero placebo patients. In the B-Well 1 trial, 127 of 650 patients (20%) versus zero of 328; in the B-well 2 trial, 106 of 570 patients (19%) versus zero of 286 patients.

Cure was defined as at least 24 weeks of a sustained HBV DNA level below the lower limit of quantification and hepatitis B surface antigen (HBsAg) loss after fixed-duration therapy.

Standard therapy typically requires long-term, often lifelong, therapy with nucleos(t)ide analogues (NA). Functional cures have been rare, according to Norah Terrault, MD, MPH, a professor of medicine and chief of Gastroenterology and Liver Diseases at Keck School of Medicine at University of Southern California in Los Angeles.

”There has been great interest to find therapies that can increase the rates of HBsAg loss and to do so with finite therapy. Individuals who achieve functional cure have very low risk for liver cancer, especially if they achieve functional cure prior to development of cirrhosis.”

The historical rate of HBsAg loss on NA is about 1% per year. The trial’s 20% rate of functional cure within 24 weeks in selected patients indicates a major step forward, although it is not a universal cure strategy.

“Still, B-Well is the most credible phase three signal to date that finite HBV functional-cure therapy is achievable, but it will initially be a selected-patient strategy rather than a replacement for standard NA treatment,” said Terrault.

Editor’s note: To read the full study, click here. To read additional coverage by Medscape, click here.