Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection

Yuen, Man‐Fung; Lim, Seng-Gee; Pleśniak, Robert; Tsuji, Keiji; Janssen, Harry L A; Pojoga, Cristina; Gadano, Adrián; Popescu, Corneliu Petru; Stepanova, Tatyana; Asselah, Tarik; Diaconescu, Gheorghe; Yim, Hyung Joon; Heo, Jeong; Janczewska, Ewa; Wong, Alexander; Idriz, Nevin; Imamura, Michio; Rizzardini, Giuliano; Takaguchi, Koichi; Andreoné, Pietro; Arbune, Manuela; Hou, Jinlin; Park, Sung Jae; Vâţă, A; Cremer, Jennifer; Elston, Robert C.; Lukić, Tamara; Quinn, Geoff; Maynard, Lauren; Kendrick, Stuart; Plein, Helene; Campbell, Fiona; Paff, Melanie; Theodore, Dickens

doi:10.1056/nejmoa2210027

Cited by 128 publications

(75 citation statements)

References 23 publications

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“…The achievement of HDV cure might hypothetically be obtained using two therapeutic strategies, one focused on HBsAg clearance and another pursuing dual HBV and HDV replication blocking. In the first group will be the new promising anti-HBV gene therapies, such as bepirovirsen, 45 AT-2173, VIR-2218, JNJ-3989, REP-2139, etc. 46 In the second group will be agents with dual anti-HBV and anti-HDV activity, such as pegIFN or BLV ( Table 3 ).…”

Section: Future Prospectsmentioning

confidence: 99%

Bulevirtide in the Treatment of Hepatitis Delta: Drug Discovery, Clinical Development and Place in Therapy

Soriano¹,

Moreno-Torres²,

Treviño³

et al. 2023

DDDT

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It has been ten years since the identification of NTCP as the cell surface receptor for HBV and HDV entry into hepatocytes. The search for molecules interfering with the binding of NTCP and HBV/HDV led to design bulevirtide (BLV). This large polypeptide mimics a region of the pre-S1 HBsAg and blocks viral entry by inhibitory competition. BLV was initially tested in cell cultures, animal models and more recently in Phase I–III human trials (called ‘MYRS’). As monotherapy or in combination with peginterferon, BLV is well tolerated and exhibits potent antiviral activity. Plasma viremia significantly declines and/or becomes undetectable in more than 75% of patients treated for >24 weeks. However, serum HBsAg concentrations remain unchanged. No selection of BLV resistance in HBV/HDV has been reported in vivo to date. BLV is administered subcutaneously once daily at doses between 2 and 10 mg. BLV received conditional approval in Europe in 2020 to treat chronic hepatitis delta. The advent of peginterferon lambda or new specific anti-HDV antivirals (lonafarnib, etc.) will open the door for combination therapies with BLV. Since there is no stable reservoir for HDV-RNA within infected hepatocytes, viral clearance might be achieved using antivirals for a minimum timeframe. This is what happens in hepatitis C combining several antivirals, curing nearly all patients treated for 3 months. Clearance of HDV-RNA genomes may occur despite HBV persistence as cccDNA or chromosome integrated HBV-DNA within hepatocytes. This is supported by cases of HDV elimination using BLV despite persistence of serum HBsAg. Another path for HDV cure will derive from achieving HBsAg clearance, the goal of new promising anti-HBV gene therapies (bepirovirsen, etc.). In summary, the advent of BLV has triggered a renovated interest for antiviral therapy in hepatitis delta. We envision combination therapies that will lead to HDV cure in the near future.

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Section: Future Prospectsmentioning

confidence: 99%

Bulevirtide in the Treatment of Hepatitis Delta: Drug Discovery, Clinical Development and Place in Therapy

Soriano¹,

Moreno-Torres²,

Treviño³

et al. 2023

DDDT

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“…Bepirovirsen, an ASO, was able to induce functional cure in 9-10% participants assessed at 24 weeks post-EOT. 100 However, despite the large number of ongoing trials, no compounds have reached the benchmark of inducing functional cure in ≥30% subjects. It is therefore important to understand the mechanisms of action for various novel compounds and utilize the appropriate viral biomarkers to evaluate target engagement as an interim response.…”

Section: Evaluation Of Efficacy and Target Engagement For Novel Compo...mentioning

confidence: 99%

The role of different viral biomarkers on the management of chronic hepatitis B

et al. 2023

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“…For example, results from a phase II trial of the TLR‐7 agonist vesatolimod showed no significant effect on HBsAg reduction despite the dose‐dependent induction of interferon‐stimulated genes 14 and none of the patients treated with the TLR‐8 agonist selgantolimod for 24 weeks achieved the primary endpoint of ≥1 log HBsAg decline 15 . Recently, results from the phase 2b trial “B‐Clear” investigating the efficacy and safety of 12‐ and 24‐week bepirovirsen treatment in patients with chronic HBV infection with or without concomitant NA therapy were published 16 . The primary endpoint of an HBsAg below the limit of detection and an HBV DNA level below the limit of quantification 24 weeks after end of treatment was achieved in 9% to 10% of the patients.…”

Section: Figurementioning

confidence: 99%