Efficacy and safety of bulevirtide monotherapy given at 2 mg or 10 mg dose level once daily for treatment of chronic hepatitis delta: week 48 primary end point results from a phase 3 randomized, multicenter, parallel design study

Wedemeyer, Heiner; Aleman, Soo; Brunetto, M.R.; Blank, Antje; Andreone, Pietro; Богомолов, П. О.; Chulanov, Vladimir; Mamonova, Nina; Geyvandova, Natalia; Viacheslav, Morozov; Sagalova, Olga; Stepanova, Tatyana; Manuilov, Dmitry; Suri, Vithika; An, Q.; Flaherty, John F.; Osinusi, Anu; Wiesch, Julian Schulze zur; Cornberg, Markus; Zeuzem, Stefan; Lampertico, Pietro

doi:10.1016/s0168-8278(22)00433-0

Cited by 32 publications

(59 citation statements)

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“…Taking efficacy into account and adjusting adverse effect, 2 mg over 10 mg BLV is recommended as monotherapy. However, in other studies 10 mg was inferior to 2 mg BLV when used in combination with Peg‐IFNα the basis remains unclear 2‐4 …”

Section: Figurementioning

confidence: 99%

“…However, in other studies 10 mg was inferior to 2 mg BLV when used in combination with Peg-IFNα the basis remains unclear. [2][3][4] AP&T correspondence columns are restricted to invited editorials and letters discussing papers that have been published in the journal. An invited editorial or letter must have a maximum of 500 words, may contain one table or figure, and should have no more than 10 references.…”

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confidence: 99%

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Letter: chronic HDV infection—Is ignorance bliss?

Tiwari

Khanikar

Prajapati

et al. 2023

Aliment Pharmacol Ther

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Section: Figurementioning

confidence: 99%

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confidence: 99%

Letter: chronic HDV infection—Is ignorance bliss?

Tiwari

Khanikar

Prajapati

et al. 2023

Aliment Pharmacol Ther

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“…The MYR-301 trial is the first multicenter randomized, Phase 3 study testing BLV. 23 The trial assesses the efficacy and safety of delayed BLV therapy compared to 2 mg or 10 mg daily dosing. A total of 150 patients with chronic hepatitis delta were randomized into 3 arms: i) controls (10 mg BLV for 48 weeks after 48 weeks no treatment), ii) BLV 2 mg (144 weeks followed by 96 weeks off-treatment), iii) BLV 10 mg (144 weeks followed by 96 weeks off treatment).…”

Section: Clinical Development: the Myr Trialsmentioning

confidence: 99%

“…This result is noteworthy given that most patients in the MYR-301 trial received nucleos(t)ide analogues as HBV treatment. 23 …”

Section: Histological Response To Blvmentioning

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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“…3 At interim analysis of this study, the 2 mg/day and the 10 mg/day doses of BLV showed similar efficacy. 4 The results of the ongoing phase 2b MYR-204 trial 5 exploring different dosages and combination regimens are also awaited.…”

mentioning

confidence: 99%