Expected outcomes of therapy

“The recommended endpoint of novel therapy is functional cure defined as HBsAg loss using a conventional assay for detection of HBsAg (limit of detection 0.05 IU/mL) and HBV DNA below the lower limit of quantification (i.e. < 10 IU/ml) at 24 weeks off-therapy.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“An intermediate endpoint on the pathway to functional cure is partial cure, defined as HBsAg <100 IU/ml and HBV DNA below the lower limit of quantification (i.e. < 10 IU/ml) at 24 weeks off- treatment. However, further clinical data are needed to establish that HBsAg decline to <100 IU/ml is a clinically meaningful threshold suitable for use as part of composite clinical trial endpoint.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“The panel continues supporting the recommendation that anti-HBs is not required for definition of functional cure, as HBsAg loss is maintained in over 90% of patients with or without anti-HBs in long-term follow-up with currently approved therapies but will need to be confirmed with therapies in development.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“Other goals of antiviral therapy include reduction in onward transmission (both vertical (mother-to-child) and horizontal (e.g., sexual, parenteral, nosocomial)), improvement in patient reported outcomes and quality of life as well as decreased stigma.” (opens the source at this quote in a new tab)CopyFlag

“In Asian studies, loss of HBsAg has been associated with a lower risk of HCC, especially when it occurs before the age of 50, compared to individuals who do not achieve HBsAg loss.” (opens the source at this quote in a new tab)CopyFlag

“A systematic review also showed that HBsAg loss correlates with lower rates of incident cirrhosis, hepatic decompensation, and overall and liver-related mortality, though there was substantial heterogeneity across studies for all outcomes.” (opens the source at this quote in a new tab)CopyFlag

“An additional benefit of HBsAg loss is the possibility of discontinuing NA therapy.” (opens the source at this quote in a new tab)CopyFlag

“A recent study has highlighted the importance of functional cure, which is rarely achieved with current therapies, in reducing social stigma and self-stigma and significantly improving the HRQoL of individuals living with HBV.” (opens the source at this quote in a new tab)CopyFlag

“Thirty‐eight studies and 43,924 patients were finally included. The results showed that HBsAg seroclearance was durable, with a pooled recurrence rate of 6.19% (95% CI: 4.10%–8.68%).” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“Anti‐HBs seroconversion resulted in a significantly reduced recurrence rate (RR = 0.25, p < .001). Patients who experienced HBsAg seroclearance had significantly lower HCC incidence than HBsAg‐positive (RR = 0.41, p < .001). The pooled HCC incidence after HBsAg seroclearance was 1.88%; this rate was reduced to 0.76% among patients without baseline cirrhosis.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“In total, 15,760 patients with chronic HBV infection were included; 5.6% were receiving stable antiviral treatment. Overall, 4.2% (n = 667) experienced HBsAg loss across the study period. HBsAg loss was associated with an 89% and 62% reduced risk of hepatocellular carcinoma (HCC; adjusted hazard ratio [aHR]: 0.11, 95% CI: 0.01–0.76) and all‐cause mortality (ACM; aHR: 0.38, 95% CI: 0.20–0.74), respectively. Risks of compensated cirrhosis (aHR: 0.84, 95% CI: 0.52–1.35) and decompensated liver disease (aHR: 0.74, 95% CI: 0.37–1.48) were lower after HBsAg loss, but did not reach significance.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“For individuals who have cleared HBsAg, one study reported an annual HCC incidence of 0.86% overall, 2.42% in those with cirrhosis, 0.43% in those without cirrhosis, 1.07% for males, 0.57% for females, 1.21% if ≥50 years, and 0.33% if <50 years” (opens the source at this quote in a new tab)CopyFlag

“In a meta-analysis of 24 studies of 33,838 persons who cleared HBsAg, the pooled proportions of HCC occurrence ranged from 0.35% to 0.78% per year following treatment-induced or spontaneous HBsAg loss, respectively.” (opens the source at this quote in a new tab)CopyFlag

“Although progression of liver disease to cirrhosis or hepatic decompensation generally stops when patients lose HBsAg unless other causes of liver injury are present (eg, heavy alcohol consumption or nonalcoholic fatty liver), the risk of HCC persists, particularly if HBsAg loss occurred in patients older than 50 years or in those with cirrhosis or coinfection with HCV or hepatitis D virus (HDV) (128, 130–132).” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“At Week 72, 24 weeks after stopping NrtI therapy, 79% (233/295) of these participants met the primary endpoint. Of the 233 participants who met the primary endpoint at Week 72, 91% (211/233) maintained response off all HBV treatment at Week 96.” (opens the prescribing information at this quote)CopyFlag

“Through Week 96, among the 84 HIBSAGO recipients who discontinued NrtI therapy but did not achieve the primary endpoint at Week 72 (62 participants) or who achieved the primary endpoint but did not maintain a sustained response at Week 96 (22 participants), one participant met criteria to restart NrtI therapy.” (opens the prescribing information at this quote)CopyFlag

“Out of the 84 participants, three additional participants restarted NrtI therapy within one month of NrtI cessation without having met the protocol-defined NrtI restart criteria.” (opens the prescribing information at this quote)CopyFlag

“Across the two trials, 24% of patients who received Hibsago met the requirements to stop their existing medicine, compared with none who received placebo. Twenty-four weeks after stopping all hepatitis B treatment, 19% of patients who received Hibsago still had the virus under control, and a protein that signals hepatitis B infection (HBsAg) could not be detected in their blood.” (opens the source at this quote in a new tab)CopyFlag

“Exploratory analyses also showed bepirovirsen reduced HBsAg to ≤100 IU/ml in 49% of participants (598 of 1220) in the overall study population, and in 62% of bepirovirsen recipients in the ≤1000 IU/ml (476 of 768) sub-group” (opens the source at this quote in a new tab)CopyFlag