Required nucleos(t)ide analog reverse transcriptase inhibitor therapy

“HIBSAGO is administered by subcutaneous injection and must be used in combination with NrtI therapy.” (opens the prescribing information at this quote)
“HIBSAGO must be used in combination with NrtI therapy. Refer to the NrtI prescribing information for additional information.” (opens the prescribing information at this quote)

Nucleos(t)ide analog therapy in B-Well 1 and B-Well 2: continuation, cessation, and restart

“were receiving stable NrtI therapy (defined as no changes due to loss of virologic control for ≥6 months before the start of the trial and no plans for changes over the duration of the trial)” (opens the prescribing information at this quote)
“From Week 25 to 48, participants continued to receive their NrtI therapy without HIBSAGO or placebo.” (opens the prescribing information at this quote)
“At Week 48, participants who met the prespecified NrtI cessation eligibility criteria discontinued NrtI therapy.” (opens the prescribing information at this quote)
“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. Protocol-defined criteria to restart NrtI therapy included HBV DNA >20,000 IU/mL at a single visit, HBV DNA >2,000 IU/mL at two sequential visits, confirmed HBeAg reversion, or clinical/hepatic decompensation. 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)

“Participants who have documented chronic HBV infection ≥6 months prior to screening and currently receiving stable NA therapy defined as no changes to their NA regimen from at least 6 months prior to Screening and with no planned changes to the stable regimen over the duration of the study.” (opens the source at this quote in a new tab)
“Participants who are willing and able to cease their NA treatment in accordance with the protocol.” (opens the source at this quote in a new tab)

Nucleos(t)ide analogs used with bepirovirsen in clinical trials: entecavir and tenofovir

“Entecavir (ETV) and tenofovir (TFV) are the most commonly used NAs” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quote
“NAs such as lamivudine and adefovir were used in only 4 of 227 (1.8%) On‐NA participants in B‐Clear.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quote
“the NCA PK parameters from 5 subjects receiving TAF in the B‐Clear study were similar to the published data on TAF (Table 3).” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quote

Nucleos(t)ide analog therapy at baseline in B-Together

Current NA therapy	Arm 1 (bepirovirsen 24 weeks), n (%)	Arm 2 (bepirovirsen 12 weeks), n (%)	Total, n (%)
TAF or TDF	“33 (61)”	“37 (70)”	“70 (65)”
Entecavir	“19 (35)”	“12 (23)”	“31 (29)”
Other	“2 (4)”	“4 (8)”	“6 (6)”

“Other NA medications included tenofovir, tenofovir disoproxil, lamivudine or tenofovir alafenamide.” (opens the source at this quote in a new tab)
“currently receiving stable NA therapy (defined as no changes to their NA regimen from at least 6 months prior to screening and with no planned changes to the stable regimen over the duration of the study) except telbivudine.” (opens the source at this quote in a new tab)

Pharmacokinetic interaction with entecavir and tenofovir

“Bepirovirsen plasma pharmacokinetic parameters and concentration–time profiles in patients with chronic HBV in the CS3 study (NCT02981602) were similar with or without ETV or TFV coadministration, indicating no effect of NA coadministration on bepirovirsen pharmacokinetics.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quote
“In patients with chronic HBV receiving both bepirovirsen and ETV or TFV in the B‐Clear study (NCT04449029), NA plasma concentrations and pharmacokinetic parameters were similar to those published without bepirovirsen coadministration, suggesting no effect of bepirovirsen coadministration on NA pharmacokinetics.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quote

Antiviral activity in combination with entecavir or tenofovir and cross-resistance

“Combining bepirovirsen with entecavir or tenofovir disoproxil fumarate in HepG2.2.15 cells (HBV genotype D, transfection-based delivery) resulted in no antagonism and greater reductions of intracellular HBV DNA by qPCR compared to the individual drugs.” (opens the prescribing information at this quote)
“Cross-resistance between bepirovirsen and NrtIs including entecavir and tenofovir is not expected.” (opens the prescribing information at this quote)

Peginterferon alfa-2a: concomitant use not recommended

“Concomitant administration of HIBSAGO and peginterferon alfa-2a is not recommended due to the potential for an exacerbated risk of increased ALT, decreased platelet count, and immune-mediated effects.” (opens the prescribing information at this quote)

Antiretroviral therapy in HIV and HBV coinfection

“Advise patients living with HIV who are taking NrtI therapy for both HIV and HBV to not discontinue NrtI therapy except under the direct supervision of an HIV healthcare provider” (opens the prescribing information at this quote)

“Must be on uninterrupted antiretroviral therapy (ART) containing at least tenofovir disoproxil (TDF) or tenofovir alafenamide (TAF) plus lamivudine (3TC) or emtricitabine (FTC)” (opens the source at this quote in a new tab)

Concomitant medications restricted in B-Well 1 and B-Well 2

“Currently taking, or took within 3 months of screening, any immunosuppressing drugs (e.g., prednisone), other than a short course of therapy (≤2 weeks) or topical/inhaled steroid use.” (opens the source at this quote in a new tab)
“Currently taking, or has taken within 12 months of Screening, any interferon containing therapy.” (opens the source at this quote in a new tab)
“Participants requiring anti coagulation therapies (e.g., warfarin, Factor Xa inhibitors) or anti-platelet agents (like clopidogrel or aspirin) unless treatment can safely be discontinued throughout duration of the study, by the discretion of the investigator. Occasional use is permitted.” (opens the source at this quote in a new tab)
“Prior treatment with any oligonucleotide or siRNA within 12 months prior to the first dosing day.” (opens the source at this quote in a new tab)