Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection
List of authors.
Man-Fung Yuen, M.D., Ph.D., D.Sc., Seng-Gee Lim, M.B., B.S., M.D., Robert Plesniak, M.D., Ph.D., Keiji Tsuji, M.D., Ph.D., Harry L.A. Janssen, M.D., Ph.D., Cristina Pojoga, M.D., Ph.D., Adrian Gadano, M.D., Ph.D., Corneliu P. Popescu, M.D., Ph.D., Tatyana Stepanova, M.Sc., Tarik Asselah, M.D., Ph.D., Gheorghe Diaconescu, M.D., Ph.D., Hyung Joon Yim, M.D., Ph.D., Jeong Heo, M.D., Ph.D., Ewa Janczewska, Ph.D., D.Sc., Alexander Wong, M.D., Nevin Idriz, M.D., Michio Imamura, M.D., Ph.D., Giuliano Rizzardini, M.D., Koichi Takaguchi, M.D., Ph.D., Pietro Andreone, M.D., Manuela Arbune, M.D., Ph.D., Jinlin Hou, M.D., Sung Jae Park, Ph.D., Andrei Vata, M.D., Ph.D., Jennifer Cremer, Pharm.D., Robert Elston, Ph.D., Tamara Lukić, M.D., Geoff Quinn, M.Sc., Lauren Maynard, M.Sc., Stuart Kendrick, Ph.D., Helene Plein, Ph.D., Fiona Campbell, B.Sc., Melanie Paff, Ph.D., and Dickens Theodore, M.D., M.P.H.
for the B-Clear Study Group*
Abstract
Background
Bepirovirsen is an antisense oligonucleotide that targets all hepatitis B virus (HBV) messenger RNAs and acts to decrease levels of viral proteins.
Methods
We conducted a phase 2b, randomized, investigator-unblinded trial involving participants with chronic HBV infection who were receiving or not receiving nucleoside or nucleotide analogue (NA) therapy. Participants were randomly assigned (in a 3:3:3:1 ratio) to receive weekly subcutaneous injections of bepirovirsen at a dose of 300 mg for 24 weeks (group 1), bepirovirsen at a dose of 300 mg for 12 weeks then 150 mg for 12 weeks (group 2), bepirovirsen at a dose of 300 mg for 12 weeks then placebo for 12 weeks (group 3), or placebo for 12 weeks then bepirovirsen at a dose of 300 mg for 12 weeks (group 4). Groups 1, 2, and 3 received loading doses of bepirovirsen. The composite primary outcome was a hepatitis B surface antigen (HBsAg) level below the limit of detection and an HBV DNA level below the limit of quantification maintained for 24 weeks after the planned end of bepirovirsen treatment, without newly initiated antiviral medication.
Results
The intention-to-treat population comprised 457 participants (227 receiving NA therapy and 230 not receiving NA therapy). Among those receiving NA therapy, a primary-outcome event occurred in 6 participants (9%; 95% credible interval, 0 to 31) in group 1, in 6 (9%; 95% credible interval, 0 to 43) in group 2, in 2 (3%; 95% credible interval, 0 to 16) in group 3, and 0 (0%; post hoc credible interval, 0 to 8) in group 4. Among participants not receiving NA therapy, a primary-outcome event occurred in 7 participants (10%; 95% credible interval, 0 to 38), 4 (6%; 95% credible interval, 0 to 25), 1 (1%; post hoc credible interval, 0 to 6), and 0 (0%; post hoc credible interval, 0 to 8), respectively. During weeks 1 through 12, adverse events, including injection-site reactions, pyrexia, fatigue, and increased alanine aminotransferase levels, were more common with bepirovirsen (groups 1, 2, and 3) than with placebo (group 4).
Conclusions
In this phase 2b trial, bepirovirsen at a dose of 300 mg per week for 24 weeks resulted in sustained HBsAg and HBV DNA loss in 9 to 10% of participants with chronic HBV infection. Larger and longer trials are required to assess the efficacy and safety of bepirovirsen. (Funded by GSK; B-Clear ClinicalTrials.gov number, NCT04449029. opens in new tab.)作者: StephenW 时间: 2022-11-9 11:00