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“The approval was supported by results from the B-WELL phase III trials showing functional cure rates of 19% in adults with ≤3000 IU/ml HBsAg, compared to current standard of care alone, which typically achieves less than 1% functional cure rate after one year of treatment.” (opens the source at this quote in a new tab)CopyFlag

“a functional cure rate of 26% (200 of 768 vs. 0 of 393 in the placebo group, with p<0.001 in both trials) was achieved in participants with ≤1000 IU/ml HBsAg level” (opens the source at this quote in a new tab)CopyFlag

“The current standard of care typically requires lifelong therapy, with functional cure rates achieved in less than 1% of patients.” (opens the source at this quote in a new tab)CopyFlag

“All the patients were receiving stable nucleoside or nucleotide analogue (NA) therapy and had an HBsAg level of more than 100 to 3000 IU per milliliter.” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“The percentage of patients with a functional cure at week 72 was significantly higher with bepirovirsen than with placebo both in the B-Well 1 trial (in 127 of 650 patients [20%] vs. none of 328 patients) and in the B-Well 2 trial (in 106 of 570 patients [19%] vs. none of 286 patients).” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“NAs effectively suppress HBV DNA but rarely achieve HBsAg loss (0–3% after long-term NA therapy), while IFN therapy is limited by safety and tolerability concerns” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“Bepirovirsen has shown sustained HBsAg loss in approximately 9–10% of participants after 24 weeks of finite treatment” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“PEG-IFNα offers a finite-duration treatment with modest functional cure (<10%)” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“Dosing in latest clinical trials at the time of writing” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“Common adverse events reported in latest clinical trials at the time of writing” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“Bepirovirsen is an unconjugated 20-mer ASO with a class II CpG motif that targets a conserved region in the HBV genome. Aside from its primary effect through complementary nucleotide binding, bepirovirsen can mediate TLR activity” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“Bepirovirsen is now the only HBV RNAi therapeutic that has progressed to phase III clinical trials.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“The efficacy of GSK3389404 was weaker than that of bepirovirsen.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“The above trials demonstrated that single-agent siRNAs or ASOs cannot induce a high rate of functional cure in all patients.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“We conducted a phase 2, multicenter, randomized, controlled, adaptive, open-label platform trial that included the evaluation of 48 weeks of treatment with xalnesiran at a dose of 100 mg (group 1), xalnesiran at a dose of 200 mg (group 2), xalnesiran at a dose of 200 mg plus 150 mg of ruzotolimod (group 3), xalnesiran at a dose of 200 mg plus 180 μg of pegylated interferon alfa-2a (group 4), or a nucleoside or nucleotide analogue (NA) alone (group 5)” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“Among 159 participants (30, 30, 34, 30, and 35 in groups 1 through 5, respectively), the primary end-point event occurred in 7% (95% confidence interval [CI], 1 to 22) of those in group 1, in 3% (95% CI, 0 to 17) of those in group 2, in 12% (95% CI, 3 to 28) of those in group 3, in 23% (95% CI, 10 to 42) of those in group 4, and in none (95% CI, 0 to 10) of those in group 5.” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“HBsAg loss with or without seroconversion occurred only in participants with a screening HBsAg level below 1000 IU per milliliter.” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“In groups 1 through 5, respectively, grade 3 or 4 adverse events occurred in 17%, 10%, 18%, 50%, and 6% of the participants, with the most frequent event being an elevated alanine aminotransferase level.” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“Among 121 participants, 58 (48%) met NA stopping criteria and 40 (33%) discontinued NA.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“Among participants who remained off NA, five achieved and maintained HBsAg loss (HBsAg <0.05 IU/ml) and HBV DNA undetectable (HBV DNA <10 IU/ml); all were in treatment arms with an immunomodulator.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“Of the 40 participants who discontinued NA, 19 (48%) experienced virological relapse (VR), three (8%) of whom further developed clinical relapse.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“In part I (cohorts 1–3), virally suppressed participants with chronic HBV infection naive to BRII-179 were randomized 1:1:1 to receive 48 weekly doses of PEG-IFNα alone or in combination with 13 doses of elebsiran (200 mg or 100 mg) administered every 4 weeks.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“In part I, at 24 weeks post-EOT, HBsAg loss was observed in 4 out of 19 (21.1%) participants receiving elebsiran 200 mg plus PEG-IFNα, 6 out of 18 (33.3%) participants receiving elebsiran 100 mg plus PEG-IFNα and 1 out of 18 (5.6%) participants receiving PEG-IFNα monotherapy.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“In part II, HBsAg loss was observed in 9 out of 31 (29.0%) participants at 24 weeks post-EOT, with a higher response among BRII-179 anti-HBs responders (8 out of 19 participants, 42.1%) compared with nonresponders (1 out of 12 participants, 8.3%).” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“ALT increases of grade 3 were observed in 2 of 19 (10.5%) of cohort 2 and 5.6% (1 of 18) of cohort 3 participants” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“Between July 2, 2020, and Nov 2, 2021, 124 individuals were screened for eligibility, 84 of whom were enrolled (15 in cohort 1, 15 in cohort 2, 18 in cohort 3, 18 in cohort 4, 13 in cohort 5, and five in cohort 6).” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“Six participants (one in cohort 2, three in cohort 4, and two in cohort 5) had sustained HBsAg seroclearance through to 24 weeks after the end of treatment. No participants receiving VIR-2218 monotherapy (cohort 1) or VIR-2218 plus pegylated interferon-alfa-2a 12-week regimen (cohort 6) had HBsAg seroclearance.” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“Two (13%) participants in cohort 1 had elevations in alanine aminotransferase, compared with 13 (87%) participants in cohort 2, 15 (83%) in cohort 3, 17 (94%) in cohort 4, 11 (85%) in cohort 5, and three (60%) in cohort 6.” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“Tobevibart was administered at 300 mg every 4 weeks; elebsiran, at 200 mg every 4 weeks” (opens the source at this quote in a new tab)CopyFlag

“Tobevibart and elebsiran without or with PEG-IFNα resulted in HBsAg loss 24 weeks post-end of treatment in 17% (3/18) and 21% (3/14) of participants with baseline HBsAg<1,000 IU/mL, respectively. These proportions were 8% (4/51) and 16% (5/32) for tobevibart and elebsiran without or with PEG-IFNα, respectively, in all participants.” (opens the source at this quote in a new tab)CopyFlag

“Tobevibart and elebsiran without or with PEG-IFNα resulted in functional cure in 11% (2/18) and 15% (2/13) of participants with HBsAg<1000 IU/mL, respectively. These proportions were 4% (2/51) and 10% (3/30) for the combinations without or with PEG-IFNα, respectively, in all participants.” (opens the source at this quote in a new tab)CopyFlag

“As previously communicated, Phase 3 development of combinations of tobevibart and elebsiran in CHB will not move forward without a global development and commercialization partner, which has not been secured.” (opens the source at this quote in a new tab)CopyFlag

“The primary endpoint was the proportion of patients meeting predefined nucleos(t)ide analogue-stopping criteria (alanine aminotransferase <3 × upper limit of normal, HBV DNA below the lower limit of quantitation, HBeAg negative, and HBsAg <10 IU/mL) at week 48.” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“At week 48, five (5%; 90% CI 2-11) of 91 patients in the JNJ-3989 dual 40 mg group, 15 (16%; 10-24) of 92 in the JNJ-3989 dual 100 mg group, 18 (19%; 13-27) of 94 in the JNJ-3989 dual 200 mg group, eight (9%; 4-15) of 94 in the triple group, and one (2%; 0-10) of 45 in the control group met nucleos(t)ide analogue stopping criteria.” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“29 (6%) of 460 patients in the treatment phase and in ten (2%) of 460 patients in the follow-up phase had grade 3 or 4 adverse events.” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“Although treatment with JNJ-3989 led to a dose-dependent response for meeting nucleos(t)ide analogue-stopping criteria, it rarely led to HBsAg seroclearance.” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“REEF-2, a phase IIb, double-blind, placebo-controlled, randomized study, enrolled 130 nucleos(t)ide analogue (NA)-suppressed hepatitis B e-antigen (HBeAg)-negative patients with CHB” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“At follow-up Week 24, no patients achieved the primary endpoint of functional cure (off-treatment hepatitis B surface antigen [HBsAg] seroclearance). No patients achieved functional cure at follow-up Week 48.” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“Off-treatment HBV DNA relapse and alanine aminotransferase increases were less frequent in the active arm, with 7/77 (9.1%) and 11/41 (26.8%) patients in the active and control arms, respectively, restarting NAs during follow-up.” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“In total, 48 patients (HBeAg positive, n = 11; HBeAg negative, n = 37) were enrolled; 47 reached follow-up week 48 (FUW48). Of the 48 patients, 31 (64.6%) achieved the primary endpoint; one achieved HBsAg seroclearance (<0.05 IU/ml) at both W24 and FUW48 after stopping NA.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“At W24, 15/48 (31.3%) patients met NA stopping criteria; 11/15 (73.3%) remained off NA by FUW48. One patient achieved functional cure at FUW48.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“Most patients had pronounced HBsAg reductions from baseline, no additional benefit from PegIFN-α2a, and did not achieve functional cure.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“The IM-PROVE I study was a Phase 2a proof-of-concept study in 43 NA- suppressed, HBeAg-negative CHB subjects who received 4 doses of imdusiran (IDR) (60 mg every 8 weeks) prior to randomization to 24 weeks or 12 weeks of IFN with or without additional imdusiran doses.” (opens the source at this quote in a new tab)CopyFlag

“Six subjects in this study achieved functional cure after NA d/c; 3 additional subjects had HBV DNA <LLOQ with low HBsAg levels during NA d/c follow-up.” (opens the source at this quote in a new tab)CopyFlag

“Functional cure rates in IM-PROVE I were highest amongst subjects who received 6 doses of imdusiran (60 mg every 8 weeks) and 24 weeks of weekly IFN starting at Week 28, compared to those that received shorter courses of imdusiran (4 doses) and/or IFN (12 weeks)” (opens the source at this quote in a new tab)CopyFlag

“Significant ALT flares were not observed in the subjects that achieved FC, although IFN treatment led to asymptomatic Gr 1 to Gr 3 ALT elevations in several subjects across the study cohorts” (opens the source at this quote in a new tab)CopyFlag

“These participants received subcutaneous imdusiran as a single dose of 60 mg, 90 mg, or 180 mg (part 2) or as repeat doses of 60 mg or 90 mg every 4, 8, or 12 weeks for up to 48 weeks (part 3).” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“All 83 enrolled participants received at least one dose of imdusiran or placebo and were included in the safety analyses. Across all parts, no participants discontinued imdusiran owing to an adverse event and no dose-related trends in reported treatment-emergent adverse events were observed across groups. There were no deaths.” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“Twenty-four virally suppressed, HBeAg-negative CHB patients on stable nucleos(t)ide analog therapy were enrolled” (opens the source at this quote in a new tab)CopyFlag

“Treatment-related adverse events occurred in 73% of healthy subjects and 71% of CHB patients and were primarily mild or moderate injection-site reactions and headaches. No treatment-related serious adverse events, discontinuations, or deaths were observed.” (opens the source at this quote in a new tab)CopyFlag

“HBsAg loss was achieved in 3 (15.0%) patients with very low baseline HBsAg (≤1.5 IU/mL), was maintained through the end of the study in 2 patients, and was accompanied by anti-HBs seroconversion.” (opens the source at this quote in a new tab)CopyFlag

“Functional cure could not be assessed, as nucleos(t)ide discontinuation criteria were not prespecified.” (opens the source at this quote in a new tab)CopyFlag

“siRNA monotherapy is generally safe but has produced modest HBsAg declines (1–2 log10 IU/mL), which plateau after 16–20 weeks and are not associated with HBsAg loss. Functional cure following siRNA therapy has only been reported after sequential interferon-α therapy.” (opens the source at this quote in a new tab)CopyFlag

“In contrast, in a phase 2b study of bepirovirsen (an ASO), with or without NA, rapid HBsAg reductions were observed, with up to 26% achieving HBsAg loss at the end of treatment and 9%–10% maintaining loss after treatment cessation.” (opens the source at this quote in a new tab)CopyFlag

“AHB-137 and bepirovirsen share the same target sequence but differ in pharmacological structure. Bepirovirsen follows a conventional single-gap (5–10–5) gapmer architecture with a continuous central DNA gap flanked by terminal 2′-MOE modifications, whereas AHB-137 adopts a multi-segment structural design in which the gap is divided into shorter segments separated by modified regions, with additional site-specific 2′-modifications.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“In Phase 1b, 20 HBeAg-negative, nucleos(t)ide analogue (NA)-suppressed CHB patients with baseline HBsAg 100–1000 IU/mL received MAD AHB-137 (150 or 300 mg) or placebo (8:2), and 2 patients with baseline HBsAg 1000–3000 IU/mL received open-label AHB-137 300 mg.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“No serious adverse events, deaths or discontinuations occurred.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“Transaminase elevations were self-limiting; one Grade 3 ALT elevation in the 300 mg CHB cohort coincided with rapid HBsAg loss.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“cross-trial comparisons should be interpreted with caution due to the differences in baseline HBsAg range, sample size, and study design.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“This phase 1b, randomised, open-label, multicentre trial included participants with chronic HBV infection aged between 18 and 55 years who had normal liver function, were receiving stable nucleos(t)ide therapy, and had non-detectable HBV DNA for 12 months or more.” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“VRON-0200 was well tolerated, with 38 treatment-related adverse events reported (four of grade 2, 34 of grade 1); no treatment-related serious adverse events, discontinuations, or clinical laboratory abnormalities, including liver function test results, were reported.” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“In groups 1 and 2, at day 360, 23 (85%) of 27 participants had sustained or continued HBsAg declines (12 [52%] of 23 had reductions of >50%) and four (15%) participants had declines of 1 log10 IU/mL or more from baseline.” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“In group 3, the addition of investigational antivirals resulted in rapid and profound HBsAg declines within 7 days (all seven [100%] participants treated with elebsiran plus tobevibart had HBsAg concentrations <2 IU/mL; one [14%] had HBsAg concentrations below the LLOD), regardless of baseline HBsAg concentrations.” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag