Inside the Be-Well Trials: Design, Population, and Patient Selection

In "Inside the Be Well Trials: Design, Population, and Patient Selection," the panel walks through why the Be Well trials targeted a specific surface antigen range.

Dr. Chung turns to the Be-Well phase 3 trials, which evaluated bepirovirsen in virologically suppressed patients with chronic hepatitis B, and asks Dr. Gish to describe the trial design, patient demographics, and the rationale for limiting enrollment to a specific surface antigen range.

Dr. Gish explains that Be-Well 1 and Be-Well 2 were double-blind, placebo-controlled trials in randomized, non-cirrhotic adults, with no pediatric data available. The drug was given as a weekly subcutaneous injection over a finite 24-week course, in patients already stable on nucleoside or nucleotide analog therapy such as entecavir or a tenofovir formulation. The surface antigen window of 100 to 3,000 was chosen based on phase 2 data showing a clear relationship between lower to intermediate surface antigen levels and a stronger functional cure effect. Eligible patients discontinued their nucleoside or nucleotide therapy under defined stopping rules at week 48, with functional cure assessed at week 72, off both bepirovirsen and, in some patients, off nucleoside therapy entirely. Dr. Gish asks Dr. Chung what proportion of his own patients fall within the trial’s surface antigen inclusion range.

Dr. Chung estimates it is a sizable minority, roughly 30% to 35% of patients in his practice with chronic hepatitis b, underscoring the importance of characterizing every patient's surface antigen level going forward.

Dr. Gish then raises quantitative surface antigen testing, which he has used for a decade to track patients' status and trajectory, and asks whether a patient under 100 IU might reasonably just wait to see if they clear spontaneously on nucleoside therapy. Dr. Chung agrees this is a strong point, noting that prior nucleoside discontinuation studies showed some patients achieving functional cure or surface antigen clearance after stopping long-term suppressive therapy, with the best outcomes concentrated in exactly that under-100 group, making a wait-and-see conversation a fair option for these patients.

Up next, in "Weighing Efficacy and Safety Data for an Emerging Hepatitis B Therapy," the experts weigh the efficacy and safety data these trials produced.