Hibsago (bepirovirsen) is filed as Hepatitis B virus (HBV) messenger RNA-directed antisense oligonucleotide. The sections below restate public label fields stored for this profile.
1 INDICATIONS AND USAGE HIBSAGO is indicated in combination with nucleos(t)ide analog reverse transcriptase inhibitor (NrtI) therapy for treatment of chronic hepatitis B virus (HBV) infection in adult patients without cirrhosis: • who have been on NrtI therapy for at least 6 months and have suppressed HBV deoxyribonucleic acid (DNA), and • who have HBV surface antigen (HBsAg) levels less than or equal to 3,000 IU/mL as determined by an FDA-authorized test [see Dosage and Administration ( 2.2 )] . HIBSAGO is a hepatitis B virus (HBV) mRNA-directed antisense oligonucleotide (ASO) indicated in combination with nucleos(t)ide analog reverse transcriptase inhibitor (NrtI) therapy for treatment of chronic HBV infection in adult patients without cirrhosis: • who have been on NrtI therapy for at least 6 months and have suppressed HBV deoxyribonucleic acid (DNA), and • who have HBV surface antigen (HBsAg) levels less than or equal to 3,000 IU/mL as determined by an FDA-authorized test. ( 2.2 )
12.1 Mechanism of Action HIBSAGO is an antiviral drug against HBV [see Microbiology ( 12.4 )] .
WARNING: ON-TREATMENT HEPATIC FLARES AND THROMBOCYTOPENIA On-Treatment Hepatic Flares HIBSAGO may cause on-treatment hepatic flares with increases in ALT of >20-40x ULN associated with decline in HBsAg. Some cases were associated with hyperbilirubinemia. Most occurred in the first 12 weeks of treatment and resolved when treatment was interrupted or permanently discontinued [see Warnings and Precautions ( 5.1 ), Adverse Reactions ( 6.1 )] . ALT and total bilirubin must be measured prior to initiation of HIBSAGO and frequently monitored during treatment [see Dosage and Administration ( 2.4 ), Warnings and Precautions ( 5.1 )] . Do not initiate HIBSAGO in patients with evidence of acute hepatic impairment or cirrhosis [see Contraindications ( 4 )] . Interruption of treatment, followed by reducing the dose or discontinuation of HIBSAGO, may be necessary based on the results of liver laboratory tests [see Dosage and Administration ( 2.4 )] . Thrombocytopenia HIBSAGO may cause reductions in platelet counts that may result in sudden and unpredictable thrombocytopenia, which can be life-threatening. Prior to starting HIBSAGO, obtain a platelet count to ensure the patient is eligible for treatment [see Contraindications ( 4 )] . HIBSAGO is contraindicated in patients with a platelet count below 100 x 10 9 /L prior to initiation of treatment. During treatment, monitor platelet counts weekly if values are 75 x 10 9 /L or greater, and more frequently if values are less than 75 x 10 9 /L [see Dosage and Administration ( 2.4 ), Warnings and Precautions ( 5.2 )] . If a patient develops signs or symptoms of thrombocytopenia, obtain a platelet count as soon as possible. The patient should not receive additional doses of HIBSAGO unless platelet counts return to 100 x 10 9 /L or greater. If platelet count falls below 50 x 10 9 /L, treatment with HIBSAGO should be permanently discontinued [see Dosage and Administration ( 2.4 ), Warnings and Precautions ( 5.2 )] . WARNING: ON-TREATMENT HEPATIC FLARES AND THROMBOCYTOPENIA See full prescribing information for complete boxed warning. On-Treatment Hepatic Flares • HIBSAGO may cause on-treatment hepatic flares with increases in ALT of >20-40x ULN associated with decline in HBsAg. Some cases were associated with hyperbilirubinemia. ( 5.1 ) • Evaluating liver laboratory enzymes prior to treatment and periodic monitoring during treatment is necessary for appropriate dosing. ( 2.4 , 5.1 ) Thrombocytopenia • HIBSAGO may cause reductions in platelet count that may result in sudden and unpredictable thrombocytopenia, which can be life‑threatening. ( 5.2 ) • Evaluating platelet levels prior to treatment and periodic monitoring during treatment is necessary for appropriate dosing. ( 2.4 , 4 , 5.2 )
5 WARNINGS AND PRECAUTIONS • Worsening renal function has been observed with HIBSAGO. Evaluating eGFR and urine albumin‑creatinine ratio (uACR) prior to treatment and monitoring eGFR during treatment is necessary for appropriate dosing. ( 2.4 , 5.3 ) • Serious inflammatory and immune adverse reactions have occurred. If signs and symptoms suggestive of vasculitis/immune-associated events occur, and no alternative cause is identified, permanently discontinue treatment with HIBSAGO. ( 5.4 ) • A serious adverse reaction has been observed with improper administration of HIBSAGO. Ensure that injection sites are rotated from one week to the next and that the two injections are separated by at least 2 inches (5 cm). ( 5.5 ) • Exacerbations of HBV may occur after discontinuation of anti-HBV therapy. Frequent monitoring is important to assess the need for resumption of HBV treatment. ( 5.6 ) • Patients taking nucleos(t)ide analog reverse transcriptase inhibitor therapy for HIV-1 and HBV coinfection must not stop this therapy unless an HIV healthcare provider has directed them to do so. ( 5.7 ) • HIBSAGO is not recommended in patients with Hepatitis D Virus (HDV) coinfection due to the potential for an exacerbated risk of clinically significant ALT increases. ( 5.8 ) 5.1 On-Treatment Hepatic Flares During treatment with HIBSAGO, increases in ALT ≥3 x ULN to 69 x ULN were observed in clinical trials [see Adverse Reactions ( 6.1 )] . Most ALT increases occurred in the first 12 weeks of treatment (typically between Weeks 5 to 10), started to resolve within 2 weeks, and were not associated with any clinical signs or symptoms of liver dysfunction. The ALT increases were temporally associated with a preceding or concurrent decline in HBsAg suggesting host immune response. Two percent of participants receiving HIBSAGO had ALT increases ≥20 x ULN that resolved when treatment was interrupted or permanently discontinued. There have been isolated cases of ALT increases associated with an increase in total bilirubin up to 4 x ULN that resolved when treatment was permanently discontinued. ALT and total bilirubin must be measured prior to initiation of treatment. Do not initiate HIBSAGO in patients with evidence of acute hepatic impairment or cirrhosis [see Contraindications ( 4 )] . During and after HIBSAGO treatment, follow the recommended monitoring for ALT and total bilirubin and the treatment recommendations as specified in Table 1 [see Dosage and Administration ( 2.4 )]. In all patients, the minimum recommended on-treatment monitoring of ALT and total bilirubin is weekly through Week 12 and every other week from Weeks 12 through 24, but more frequent monitoring may be necessary. In addition, HIBSAGO dose reduction or temporary or permanent discontinuation of HIBSAGO may be necessary based on the results of liver laboratory testing. In all patients with abnormal values at the time of HIBSAGO discontinuation, obtain ALT and total bilirubin values at 4, 12, and 24 weeks post-treatment to assess recovery of ALT values to within the normal range, as appropriate [see Dosage and Administration ( 2.4 )]. 5.2 Thrombocytopenia HIBSAGO may cause reductions in platelet count at any time during treatment that may result in sudden and unpredictable thrombocytopenia that can be life-threatening. In the HIBSAGO clinical trials, two participants reported serious adverse reactions of thrombocytopenia <50 × 10⁹/L, including one participant with immune thrombocytopenia [see Adverse Reactions ( 6.1 )] . In addition, a gradual, dose-dependent decline in platelet count was observed in most patients that continued to worsen while on HIBSAGO. Platelet Monitoring and Dosing Platelet count must be measured prior to initiation of treatment. Do not initiate HIBSAGO in patients with a platelet count below 100 x 10 9 /L [see Contraindications ( 4 )] . In patients with platelet count below the normal range but ≥100 x 10 9 /L, rule out cirrhosis before initiating HIBSAGO [see Contraindications ( 4 )] . During and after HIBSAGO treatment, follow recommended monitoring and treatment recommendations for platelet count as specified in Table 2 [see Dosage and Administration ( 2.4 )] . In all patients, the minimum recommended on-treatment monitoring of platelet counts is weekly through Week 24, but more frequent monitoring may be necessary. In addition, HIBSAGO treatment interruption or permanent discontinuation may be necessary based on the results of platelet testing. If platelet count falls below 50 x 10 9 /L, permanently discontinue treatment with HIBSAGO and consider corticosteroid treatment in consultation with an expert. In all patients with abnormal values at the time of HIBSAGO discontinuation, obtain repeat platelet counts 4 and 12 weeks post-treatment to assess for platelet count recovery, as appropriate. Symptoms of Thrombocytopenia Symptoms of thrombocytopenia can include unusual or prolonged bleeding (e.g., petechiae, easy bruising, hematoma, subconjunctival bleeding, gingival bleeding, epistaxis, hemoptysis, irregular or heavier than normal menstrual bleeding, hematemesis, hematuria, hematochezia, melena), neck stiffness, or atypical severe headache. Instruct patients to report to their healthcare provider immediately if they experience any symptoms of thrombocytopenia. If a patient develops signs or symptoms of thrombocytopenia, treatment with HIBSAGO must be paused and a platelet count obtained as soon as possible [see Dosage and Administration ( 2.4 )] . Additional Considerations Consider the risks and benefits of treatment with HIBSAGO when treating patients who may be particularly susceptible to platelet count decreases, e.g., elderly patients, or patients with bleeding diathesis/coagulopathy, history of major bleeding events or patients taking antiplatelets, anticoagulants, or drugs that lower platelet count [see Drug Interactions ( 7.1 )]. 5.3 Worsening Renal Function In the HIBSAGO clinical trials, mean eGFR declined within 4 weeks of initiation of HIBSAGO and continued to decline during treatment. These changes were generally reversible after treatment discontinuation. The mechanism of the decrease in eGFR is not clear [see Adverse Reactions ( 6.1 )] . Obtain eGFR and uACR in all patients prior to initiation of treatment. The clinical trials excluded participants with moderate or severe renal impairment (eGFR ≤60 mL/min/1.73m 2 ) or uACR >0.3 mg/mg; insufficient data are available on the safety of HIBSAGO in these populations [see Use in Specific Populations ( 8.6 )] . Consider the risks and benefits of HIBSAGO when treating patients who may be more susceptible to renal injury [see Drug Interactions ( 7.2 )] . During and after HIBSAGO treatment, follow the recommended monitoring for eGFR and the treatment recommendations as specified in Table 3 [see Dosage and Administration ( 2.4 )] . In all patients, the minimum recommended on-treatment monitoring of eGFR is every other week through Week 24, but more frequent monitoring may be necessary. In addition, HIBSAGO treatment interruption or permanent discontinuation may be necessary based on the results of renal laboratory testing. In all patients with abnormal values at the time of HIBSAGO discontinuation, obtain repeat eGFR 4 and 12 weeks post-treatment to assess for renal function recovery, as appropriate. Although no cases of glomerulonephritis were observed with HIBSAGO administration in the clinical trials, glomerulonephritis has been observed after administration of other antisense oligonucleotides. Consider assessing for proteinuria periodically during treatment, as appropriate. If a diagnosis of glomerulonephritis is suspected or confirmed, permanently discontinue HIBSAGO and consider early initiation of immunosuppressive therapy in consultation with an expert. 5.4 Inflammatory and Immune Effects In trials with HIBSAGO, influenza-like symptoms, laboratory test changes (e.g., decreases in complement factors C3 and C4), purpuric…
4 CONTRAINDICATIONS HIBSAGO is contraindicated in patients: • with acute hepatic impairment, or cirrhosis who have mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, or C) [see Warnings and Precautions ( 5.1 )] . • with a platelet count below 100 x 10 9 /L prior to initiation of treatment [see Warnings and Precautions ( 5.2 )] . • Patients with acute hepatic impairment, or cirrhosis who have mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B or C) ( 4 , 5.1 ) • Patients with platelet count below 100 x 10 9 /L prior to initiation of treatment ( 4 , 5.2 )
Injection site reactions (≥10%); Pyrexia (≥10%); Fatigue (≥10%); Headache (≥10%)
6 ADVERSE REACTIONS The following adverse reactions are described in more detail in the Warnings and Precautions section of the labeling: • On-Treatment Hepatic Flares [see Warnings and Precautions ( 5.1 )] . • Thrombocytopenia [see Warnings and Precautions ( 5.2 )] . • Worsening Renal Function [see Warnings and Precautions ( 5.3 )] . • Inflammatory and Immune Effects [see Warnings and Precautions ( 5.4 )] . • Serious Adverse Reaction with Improper Administration [see Warnings and Precautions ( 5.5 )] . The most common adverse reactions (incidence ≥10%) are injection site reactions, pyrexia, fatigue, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of HIBSAGO in the treatment of chronic HBV infection has been evaluated in two pooled, Phase 3, placebo-controlled randomized trials (B‑Well 1 and B‑Well 2) in which 1,223 participants received at least one dose of HIBSAGO (300 mg subcutaneously, twice weekly during Weeks 1 and 2, and once weekly during Weeks 3 to 24) and 611 participants received matching placebo. The most common adverse reactions (≥10%), excluding laboratory abnormalities, reported with HIBSAGO included injection site reactions, pyrexia, fatigue, and headache. In the pooled B-Well 1 and B-Well 2 trials, 3% of participants receiving HIBSAGO and <1% of participants receiving placebo discontinued due to adverse events. The incidence of adverse reactions in the pooled safety data set (Weeks 1‑36) with HIBSAGO is shown in Table 4 . Table 4. Adverse Reactions a (All Grades) Reported in ≥3% of HIBSAGO Recipients and at a Frequency ≥2% Greater than Placebo, B-Well 1 and B-Well 2 Trials (Weeks 1-36) a Frequencies of adverse reactions are based on all adverse events, regardless of investigator assessment of causality, excluding laboratory abnormalities reported as adverse events (see Table 6 for laboratory abnormalities). b See Table 5 for a summary of the different types of injection site reactions. c Fatigue includes the preferred terms asthenia, fatigue, malaise, lethargy and sluggishness. Adverse Reaction HIBSAGO N = 1,223 Placebo N = 611 Injection Site Reactions (all types) b 57% 15% Pyrexia 20% 4% Fatigue c 16% 8% Headache 14% 12% Myalgia 8% 4% Nausea or Vomiting 5% 3% Erythema 5% <1% Pruritus 5% 2% Influenza-like illness 4% 2% Rash 3% 1% Contusion 3% 1% Cutaneous Vasculitis Adverse reactions of biopsy-confirmed vasculitis occurred in two participants treated with HIBSAGO. One participant developed arthralgia, lower limb edema, and purpuric lesions at Treatment Week 2. The second participant developed a pruritic circular lesion on the left lower limb at Treatment Week 14 which progressed to bilateral lower limb pruritic scaly lesions on Treatment Week 17. For both cases, skin biopsy confirmed leukocytoclastic vasculitis, and the events resolved with corticosteroid treatment after permanent discontinuation of HIBSAGO [see Warnings and Precautions ( 5.4 )] . Injection Site Reactions (ISRs) ISRs were the most common adverse reactions reported with HIBSAGO. The most commonly reported ISRs (all grades) in the pooled safety data set (Weeks 1‑36) are presented in Table 5 . The frequency and severity of injection site reactions decreased over time, and 99% of injection site reactions reported in HIBSAGO recipients were mild to moderate in severity. Table 5: Injection Site Reactions a (All Grades) Reported in ≥3% of HIBSAGO Recipients and at a Frequency ≥2% Greater than Placebo, B-Well 1 and B-Well 2 Trials (Weeks 1-36) Pooled Injection Site Reaction Categories b HIBSAGO N = 1,223 Placebo N = 611 a Frequencies of injection site reactions are based on all adverse events, regardless of investigator assessment of causality. b To provide accurate frequencies, pooled injection site reaction categories were constructed to combine adverse event preferred terms describing the same type of injection site reaction. c Individual participants may have reported more than one type of injection site reaction. Any injection site reaction c 57% 15% Injection site erythema 32% 2% Injection site pain 24% 6% Injection site pruritus 19% 1% Injection site bruising 19% 6% Injection site induration/swelling 13% 1% Injection site discoloration 8% <1% Injection site rash 6% <1% Injection site hematoma 4% 1% A serious adverse reaction of omental infarction requiring surgical intervention occurred at Treatment Week 11 in a participant who had four weeks of persistent erythema at the HIBSAGO injection site and in whom injection sites had not been rotated. The infarcted omentum was adherent to the peritoneum directly underlying the area of injection site at which reactive changes, including a granuloma, were seen on CT scan [see Warnings and Precautions ( 5.5 )] . Less Common Adverse Reactions Reported in Clinical Trials: The following adverse reactions occurred in <3% of participants receiving HIBSAGO and are included because of a potential causal relationship: Immune system disorders: Hypersensitivity Skin and soft tissue disorders: Angioedema Laboratory Abnormalities Table 6: Selected Laboratory Abnormalities a (Worsened from Baseline) Reported in Participants in B-Well 1 and B-Well 2 Trials (Weeks 1-36) ALT = alanine aminotransferase; AST = aspartate aminotransferase; ANC = absolute neutrophil count; eGFR = estimated glomerular filtration rate; uACR = urine albumin-creatinine ratio, ULN = upper limit of normal. Note: Each participant is only counted once per parameter with the laboratory value that represents their largest change from baseline in Weeks 1-36. Note: Japanese Society of Nephrology-Chronic Kidney Disease Initiatives (JSN-CKDI) equation was used to calculate eGFR for Japanese participants. a Information based on laboratory values reported from the central laboratory for B-Well 1 and B-Well 2 (local laboratory results were not included). Laboratory Categories HIBSAGO N = 1,223 Placebo N = 611 ALT ≥3xULN to <5xULN 10% <1% ≥5xULN to <10xULN 8% 0 ≥10xULN to <20xULN 4% 0 ≥20xULN 2% <1% AST ≥3xULN to <5xULN 6% <1% ≥5xULN to <10xULN 4% <1% ≥10xULN to <20xULN 1% <1% ≥20xULN <1% 0 Total bilirubin ≥ULN to <1.5xULN 8% 11% ≥1.5xULN to <2xULN 2% 2% ≥2xULN <1% <1% Platelets (x10 9 /L) ≥100 to <140 37% 7% ≥75 to <100 8% <1% ≥50 to <75 2% <1% ≥25 to <50 <1% 0 <25 <1% 0 ANC cells/mm 3 ≥500 to <1,000 8% 3% ≥100 to <500 1% <1% <100 0 0 eGFR ≥15 to <30% decline from baseline 51% 30% ≥30 to <50% decline from baseline 17% 6% ≥50% decline from baseline 1% <1% uACR ≥0.3 mg/mg 2% 1% ALT Increased During the first 24 weeks, <1% (n = 1) of HIBSAGO recipients had ALT ≥3x ULN with bilirubin ≥2x ULN (>35% direct bilirubin) and permanently discontinued treatment [see Warnings and Precautions ( 5.1 )] . Three other participants also permanently discontinued treatment because of ALT ≥10 x ULN for 4 or more weeks, and 53 (4%) paused treatment due to ALT increases. Decreased Platelet Counts During the first 24 weeks, two participants treated with HIBSAGO had serious adverse reactions of thrombocytopenia, with platelet counts <50 × 10⁹/L. One participant experienced platelet decline from 283 × 10⁹/L at baseline to 161× 10⁹/L at Week 5, 83 × 10⁹/L at Treatment Week 6 and a nadir of 42 × 10⁹/L at Treatment Week 7. The other participant experienced platelet decline from 261 × 10⁹/L at baseline, to 177 × 10⁹/L at Week 6, to 108 × 10⁹/L at Treatment Week 7, with a nadir of 8 × 10⁹/L at Treatment Week 8. This participant was assessed as having immune thrombocytopenia. Both participants recovered with corticosteroid treatment and permanent discontinuation of HIBSAGO [see Warnings and Precautions…
2 DOSAGE AND ADMINISTRATION • Refer to the full prescribing information for additional important dosage information. • HIBSAGO is administered by subcutaneous injection and must be used in combination with NrtI therapy. ( 2.3 ) • Weeks 1 and 2: The recommended dosage of HIBSAGO is 300 mg (administered as two 150 mg subcutaneous injections) twice a week allowing 3 or 4 days between each dose. ( 2.3 ) • Weeks 3 to 24: The recommended dosage of HIBSAGO is 300 mg (administered as two 150 mg subcutaneous injections) once a week on the same day each week. ( 2.3 ) • Laboratory tests must be measured prior to, during, and following discontinuation of treatment. ( 2.2 , 2.4 ) • Dosage modification is recommended in patients experiencing elevated liver laboratory values, platelet count reductions or eGFR decline. ( 2.4 ) 2.1 Dosage and Administration Overview • HIBSAGO therapy should be prescribed only when appropriate laboratory monitoring can be performed to manage the treatment regimen. Close laboratory monitoring is required to assess for toxicities that may necessitate dose modification, treatment interruption, or permanent discontinuation of HIBSAGO [see Dosage and Administration ( 2.4 ), Warnings and Precautions ( 5.1 , 5.2 , 5.3 )] . • HIBSAGO must be administered under the guidance and supervision of a healthcare provider for the initial dose to ensure proper injection technique. • Patients or caregivers may administer HIBSAGO after their healthcare provider determines that it is appropriate and with medical follow-up, including laboratory testing. Healthcare providers must provide proper training in subcutaneous injection technique before the patient or caregivers can administer HIBSAGO [see Dosage and Administration ( 2.5 )] . The maximum recommended duration of HIBSAGO treatment is 24 weeks [see Dosage and Administration ( 2.5 , 2.7 )] . 2.2 Testing Prior to Initiation for Patient Selection Prior to initiation of HIBSAGO for treatment of chronic HBV infection, test all patients to quantify HBsAg levels in serum or plasma to identify patients with baseline HBsAg levels less than or equal to 3,000 IU/mL [see Indications and Usage ( 1 )] . In addition, test patients for HBV DNA, ALT, AST, bilirubin, platelet count, urine albumin-creatinine ratio (uACR), and estimated glomerular filtration rate (eGFR) prior to initiation of treatment and as directed while on treatment and following treatment completion [see Indications and Usage ( 1 ), Dosage and Administration ( 2.4 ), Contraindications ( 4 ), Warnings and Precautions ( 5.1 , 5.2 , 5.3 )] . Information on FDA-authorized tests for the quantification of HBsAg levels is available at: http://www.fda.gov/CompanionDiagnostics . 2.3 Recommended Dosage HIBSAGO is for subcutaneous use only [see Dosage and Administration ( 2.5 )] . The maximum recommended duration of HIBSAGO treatment is 24 weeks [see Dosage and Administration ( 2.7 )] . HIBSAGO must be used in combination with NrtI therapy. Refer to the NrtI prescribing information for additional information. Weeks 1 and 2 The recommended dosage of HIBSAGO is 300 mg (administered as two 150 mg subcutaneous injections) twice a week allowing 3 or 4 days between each dose. Weeks 3 to 24 The recommended dosage of HIBSAGO is 300 mg (administered as two 150 mg subcutaneous injections) once a week on the same day each week. Early cessation of HIBSAGO may be considered in patients who have not achieved HBsAg <1 IU/mL by Treatment Week 12 [see Clinical Studies ( 14 )] . 2.4 Laboratory Monitoring and Dosage Modifications for Adverse Reactions During treatment with HIBSAGO, laboratory test monitoring is required to detect and manage adverse reactions. Based on laboratory test values, adjustments to HIBSAGO dosage, treatment interruption, and increased frequency of laboratory test monitoring may be required as described in Tables 1 , 2 , and 3 . Dosage Modifications Based on ALT and Total Bilirubin Values Table 1 displays the recommended ALT and total bilirubin monitoring and HIBSAGO dosage modifications due to ALT and total bilirubin value changes. Table 1. Laboratory Monitoring and Dosage Modifications of HIBSAGO Based on ALT and Total Bilirubin Values ALT = Alanine Aminotransferase, ULN = Upper Limit of Normal a If ALT or total bilirubin has increased markedly from the previous assessment, repeat laboratory testing and review the results before giving the next dose of HIBSAGO, even if the values have not yet reached the thresholds that require treatment interruption or discontinuation. b In all patients with abnormal values at the time of HIBSAGO discontinuation, obtain ALT and total bilirubin values at 4, 12, and 24 weeks post-treatment to assess recovery of ALT values to within the normal range, as appropriate. c The minimum recommended on-treatment monitoring of ALT and total bilirubin in all patients. ALT and/or Total Bilirubin a Dosage ALT and Total Bilirubin Monitoring Frequency b ALT <3x ULN No dosage adjustments required Weekly through Week 12 and every other week from Weeks 12 through 24 c ALT Increases with Total Bilirubin <1.5x ULN ALT <10x ULN No dosage adjustments required Weekly through Week 12 and every other week from Weeks 12 through 24 ALT ≥10x to <12x ULN No dosage adjustments required Increase monitoring to twice weekly until ALT is on a downward trajectory ALT ≥12x ULN Pause treatment When ALT<10x ULN, resume treatment at 150 mg once a week. If ALT continues to decline, increase dosage to 300 mg once a week. ALT ≥10x ULN for ≥4 weeks Permanently discontinue treatment Twice weekly until ALT is on a downward trajectory and then as clinically indicated ALT Increases with Total Bilirubin ≥1.5 to <2x ULN ALT ≥3x ULN Pause treatment When ALT <10x ULN and total bilirubin <1.5x ULN, resume treatment at 150 mg once a week. If ALT is on a downward trajectory, increase dosage to 300 mg once a week. Increase monitoring to twice weekly until ALT is on a downward trajectory ALT Increases with Total Bilirubin ≥2x ULN ALT ≥3x ULN Permanently discontinue treatment Twice weekly until ALT is on a downward trajectory and then as clinically indicated Dosage Modifications Based on Platelet Count Table 2 displays the recommended platelet count monitoring while on HIBSAGO treatment and HIBSAGO dosage modifications due to platelet count changes. Table 2. Laboratory Monitoring and Dosage Modifications of HIBSAGO Based on Platelet Count a If platelet count decreases by ≥30% between consecutive readings, repeat and review platelet count before administering further doses of HIBSAGO, even if platelet count is ≥100 x 10 9 /L. b In all patients with abnormal values at the time of HIBSAGO discontinuation, obtain repeat platelet counts 4 and 12 weeks post-treatment to assess for platelet count recovery, as appropriate. c The minimum recommended on-treatment monitoring of platelet counts in all patients. Platelet Count (x 10 9 /L) a Dosage Platelet Monitoring Frequency b ≥100 No dosage adjustment required Weekly c 75 to <100 Pause treatment When platelet count ≥100 x 10 9 /L, resume treatment at 300 mg once a week Weekly 50 to <75 Every 2-3 days until 3 consecutive platelet counts ≥75 x 10 9 /L 25 to <50 Permanently discontinue treatment Every 2-3 days until 3 consecutive platelet counts ≥75 x 10 9 /L <25 Daily until 2 consecutive platelet counts ≥25 x 10 9 /L Dosage Modifications Due to Renal Impairment Table 3 displays the recommended renal test monitoring while on HIBSAGO treatment and HIBSAGO dosage modifications due to renal impairment. Table 3. Laboratory Monitoring and Dosage Modification of HIBSAGO Based on eGFR eGFR = estimated glomerular filtration rate a In all patients with abnormal values at the time of HIBSAGO discontinuation, obtain eGFR at 4 weeks and 12 weeks post-treatment to monitor for renal function recovery, as appropriate. b The minimum recommended on-treatment monitoring of eGFR in all patients. eGFR Dosage eGFR Monitoring Frequency a No significant…
7 DRUG INTERACTIONS • Monitor patients for signs of bleeding and thrombocytopenia if HIBSAGO is taken concomitantly with anticoagulants, antiplatelets or drugs that decrease platelet count. ( 7.1 ) • Monitor patients for signs of worsening renal function during concomitant administration of HIBSAGO with drugs that may impair renal function. ( 7.2 ) • Concomitant administration of HIBSAGO and peginterferon alfa-2a is not recommended. ( 7.3 ) 7.1 Anticoagulants, Antiplatelets, and Drugs that Decrease Platelet Count Monitor patients for signs of bleeding and thrombocytopenia if HIBSAGO is taken concomitantly with anticoagulants, antiplatelets, or drugs that decrease platelet count [see Warnings and Precautions ( 5.2 ), Adverse Reactions ( 6.1 )] . 7.2 Drugs that Impair Renal Function Monitor patients for signs of worsening renal function during concomitant administration of HIBSAGO with drugs that may impair renal function. Refer to individual drug information before prescribing [see Warnings and Precautions ( 5.3 ), Adverse Reactions ( 6.1 )] . 7.3 Peginterferon Alfa-2a 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.
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Give patients the Medication Guide for HIBSAGO. On-Treatment Hepatic Flares Inform patients that HIBSAGO may cause elevations in ALT. Advise patients to contact their healthcare provider immediately if they experience abdominal discomfort, dark urine, or jaundice and the importance of complying with laboratory monitoring during and after treatment with HIBSAGO [see Warnings and Precautions ( 5.1 )] . Thrombocytopenia Inform patients that HIBSAGO may cause reductions in platelet count that may result in thrombocytopenia. Instruct patients to immediately report any signs of unusual or prolonged bleeding to their physician. Advise patients of the importance of complying with laboratory monitoring during and after treatment with HIBSAGO [see Warnings and Precautions ( 5.2 )] . Worsening Renal Function Inform patients that HIBSAGO may cause worsening of renal function. Advise patients of the importance of complying with laboratory monitoring during and after treatment with HIBSAGO [see Warnings and Precautions ( 5.3 )] . Inflammatory and Immune-Mediated Adverse Reactions Inform patients that HIBSAGO may cause inflammatory and immune effects. Advise patients to contact their healthcare provider if they experience influenza‑like symptoms with events such as purpuric leg rashes, cutaneous leukocytoclastic vasculitis, dermatitis, pruritus/erythematous plaque, and polyarthralgia [see Warnings and Precautions ( 5.4 )] . Administration Instruction Train patients and caregivers on the importance of proper subcutaneous administration technique, the necessity of rotating injection sites and how to use the prefilled syringe. Instruct patients and/or caregivers to read and follow the Instructions for Use each time they use HIBSAGO [see Warnings and Precautions ( 5.5 )] . HBV Exacerbation after Discontinuation of HBV Therapy Inform patients that severe acute exacerbations of HBV may occur after stopping all anti-HBV therapy. If NrtI therapy is discontinued after completing HIBSAGO treatment, advise patients of the importance of frequent monitoring to assess the possible need for resumption of HBV treatment [see Warnings and Precautions ( 5.6 )] . Risks in Patients with HBV/HIV 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 [see Warnings and Precautions ( 5.7 )] . Transmission of HBV Inform patients that it is not known if therapy with HIBSAGO will prevent transmission of HBV, and that appropriate precautions to prevent transmission of the hepatitis B virus should be taken [see Warnings and Precautions ( 5.9 )] . Trademarks are owned by or licensed to the GSK group of companies. Manufactured for GlaxoSmithKline Durham, NC 27701 ©2026 GSK group of companies or its licensor. HBS:1PI
According to its FDA label, Hibsago (bepirovirsen) is approved for: 1 INDICATIONS AND USAGE HIBSAGO is indicated in combination with nucleos(t)ide analog reverse transcriptase inhibitor (NrtI) therapy for treatment of chronic hepatitis B virus (HBV) infection in adult patients without cirrhosis: • who have been on NrtI therapy for at least 6 mont… For medical advice, please talk to your prescriber or pharmacist.
Hibsago (bepirovirsen) belongs to the Hepatitis B virus (HBV) messenger RNA-directed antisense oligonucleotide class of medications.
The FDA label lists Hibsago (bepirovirsen) as: 3 DOSAGE FORMS AND STRENGTHS Injection: 150 mg/mL of bepirovirsen as a clear, colorless to yellow sterile solution with no visible particulates in a single-dose prefilled glass syringe within a safety syringe device. Injection: 150 mg/mL solution in a single‑dose, prefilled syringe; subcutaneous route. Available strengths and packaging vary by manufacturer.
Not yet. As of the most recent FDA data we ingest, no A-rated generic equivalent is listed for Hibsago. Availability changes as patents expire.
Yes. The FDA label for Hibsago (bepirovirsen) carries a Boxed Warning. Excerpt: "WARNING: ON-TREATMENT HEPATIC FLARES AND THROMBOCYTOPENIA On-Treatment Hepatic Flares HIBSAGO may cause on-treatment hepatic flares with increases in ALT of >20-40x ULN associated with decline in HBsAg. Some cases were a…" See the full FDA label for the complete warning. For medical advice, please talk to your prescriber or pharmacist.
The FDA Enforcement Report does not show an active/ongoing recall for Hibsago (bepirovirsen) in our latest ingest. Recall data can change daily — verify at FDA.gov.
The FDA record lists the approval date for Hibsago (bepirovirsen) as 2026-10-20.
The FDA label lists GlaxoSmithKline LLC as a labeler/manufacturer of Hibsago (bepirovirsen). Multiple firms may market generics of the same molecule.
The FDA label states: "16 HOW SUPPLIED/STORAGE AND HANDLING HIBSAGO (bepirovirsen) injection is a sterile, preservative-free, clear, colorless to yellow solution for subcutaneous use. The syringes are not made with natural rubber latex. Each s…" Follow the packaging insert for the authoritative guidance.
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