The duplicate Phase 3 RCTs published in NEJM demonstrate that 20% and 19% of carefully selected chronic hepatitis B patients reached functional cure (undetectable HBsAg and HBV DNA at 24 weeks post-treatment) after 24 weeks of bepirovirsen, versus 0% on placebo—an advance rooted in antisense oligonucleotide targeting of viral RNA. This RCT design with predefined functional cure endpoints, first formalized in the 2016 FDA-EMA-AASLD-EASL consensus meeting led by Anna Lok, marks the initial Phase 3 completion after years of failed combinations. However, the MedicalXpress coverage underplays selection bias: trials excluded decompensated cirrhosis and high-viral-load patients common in high-prevalence regions, limiting generalizability. Side effects were notably higher in the active arm, raising adherence questions for real-world rollout. Connecting to broader patterns, WHO 2024 hepatitis elimination targets remain distant because current nucleos(t)ide analogs suppress but rarely cure, perpetuating lifelong therapy costs in Asia and sub-Saharan Africa where 80% of cases cluster. A 2023 Lancet Gastroenterology review on cure strategies highlights that immunomodulatory add-ons like bepirovirsen could close this gap if combination regimens push rates above 30%, yet no data address pediatric or pregnant populations. Conflicts of interest in the Hou et al. trial (industry-sponsored) warrant scrutiny, though independent editorial endorsement by Lok strengthens credibility. Long-term relapse monitoring beyond 24 weeks and cost-effectiveness modeling are absent, critical omissions for translating this 1-in-5 success into population-level impact.