Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Bepirovirsen · 7 trials · 3 indications
The number of participants who achieved FC after discontinuation of all chronic HBV treatment (bepirovirsen/placebo and NA) in the absence of rescue medication will be reported. The FC for HBV is defined as Sustained suppression (24 weeks or longer) of HBV DNA \< Lower limit of quantification (LLOQ) off all HBV treatment and HBsAg not detected with or without HBsAb after a finite duration of therapy.
HBV virologic response defined as HBV surface antigen (HBsAg) not detected and HBV deoxyribonucleic acid (DNA) less than (\<) lower limit of quantification (LLOQ).
NA indicates nucleos(t)ide analogue (NA).
Continuous 12-lead electrocardiogram (ECG) was captured by Holter monitor. QTcF was measured from 10 digital ECGs extracted from the continuous tracing after 10 minutes of rest in supine position. Baseline was defined as pre-dose value on Day 1. Change from Baseline (CFB) was calculated by subtracting post-dose visit value from Baseline value. Geometric mean and 90 percent (%) Confidence Interval (CI) of predicted CFB QTcF adjusted for placebo at Cmax following supratherapeutic single doses of Bepirovirsen was presented using concentration QTc (C-QTc) analysis using exposure-response modelling. This approach utilized pre-specified linear mixed effects model where CFB QTcF was dependent variable. Fixed-effect parameters included intercept, slope, influence of Baseline on intercept, treatment and nominal time from first dose. Participant was included as additive random effect on both intercept and slope terms.
Blood samples were collected at indicated timepoints for pharmacokinetic analysis of Bepirovirsen. Cmax calculation for this outcome measure is based on changes in model specifications and inclusion of different arms for respective outcome measures. Model includes Randomized Groups (Groups compared), injection site (arm, thigh and abdomen) as categorical covariates and log transformed Baseline weight as continuous covariate. The treatment is a factor in the model and position of a treatment as either test or reference would affect the Cmax values for a particular outcome measure due to differences in how the model accounts for variability and compares group for mean calculation. Pharmacokinetic (PK) Parameter Population included all participants in the PK concentration Population for whom valid and evaluable plasma PK parameters were derived.
Blood samples were collected at indicated timepoints for pharmacokinetic analysis of Bepirovirsen. Blood samples were collected at indicated timepoints for PK analysis of Bepirovirsen. AUC(0-inf) calculation for this outcome measure is based on changes in model specifications and inclusion of different arms for respective outcome measures. Model includes Randomized Groups (Groups compared), injection site (arm, thigh and abdomen) as categorical covariates and log transformed Baseline weight as continuous covariate. The treatment is a factor in the model and position of a treatment as either test or reference would affect the AUC(0-inf) values for a particular outcome measure due to differences in how the model accounts for variability and compares group for mean calculation.
| Arm | Type | Description |
|---|---|---|
| Bepirovirsen | EXPERIMENTAL | - |
| Placebo | PLACEBO_COMPARATOR | - |
| Participants receiving Bepirovirsen | EXPERIMENTAL | Participants will receive bepirovirsen. |
| Participants receiving Placebo | PLACEBO_COMPARATOR | Participants will receive placebo. |
| Not-on-NA participants | EXPERIMENTAL | Participants rolling over from study 209668 who have not received nucleos(t)ide analogue (NA) therapy during the parent study and remain off NAs will be included in this arm. Participants will be followed up for 33 months. Participants maintaining either functional cure (FC) or a partial response off NA treatment at Month 33 will be eligible to be followed up for an additional 2 years. No study treatment will be administered in this study. |
| On-NA participants | EXPERIMENTAL | Participants rolling over from studies 209668, 209348, 212602, 202009, 219288, and 217023 who entered the parent study on stable NA therapy and remained on NA therapy for the duration of the treatment and follow-up periods in the parent study will be included in this arm. NA cessation will occur at 3 months in 206882 for eligible and willing participants. Participants will be followed up for 33 months. Participants rolling over from studies 209668 and 209348 who stopped NA treatment and are maintaining either FC or a partial response at Month 33, and remaining off NA treatment, will be eligible to be followed up for an additional 2 years. No study treatment will be administered in this study. |
| NA-cessated participants | EXPERIMENTAL | Participants rolling over from studies 202009 and 219288 who have stopped NA treatment during the parent study will be included in this arm. Participants will be followed up for 33 months. No study treatment will be administered in this study. |
| Group 1- Severe Renal Impairment Participants | EXPERIMENTAL | Participants with severe renal impairment will receive Bepirovirsen. |
| Group 2- Moderate Renal Impairment Participants | EXPERIMENTAL | Participants with moderate renal impairment will receive Bepirovirsen. |
| Group 3-Healthy Control Participants | EXPERIMENTAL | Healthy control participants will receive Bepirovirsen. |
| Bepirovirsen: Four-Dose SC Injection | ACTIVE_COMPARATOR | Participant received four subcutaneous (SC) injections of Bepirovirsen dose level 1 on Day 1. |
| Placebo: Four SC Injections | PLACEBO_COMPARATOR | Participants received four matching placebo SC injections on Day 1. |
| Bepirovirsen: Three-Dose SC Injection | ACTIVE_COMPARATOR | Participant received three SC injections of Bepirovirsen dose level 1 on Day 1. |
| Placebo: Three SC Injections | PLACEBO_COMPARATOR | Participants received three matching placebo SC injections on Day 1. |
| Bepirovirsen Vial by HCP | EXPERIMENTAL | Participants will receive Bepirovirsen vial administered by Healthcare Professionals (HCP). |
| Bepirovirsen PFS SSD by HCP | EXPERIMENTAL | Participants will receive Bepirovirsen PFS SSD administered by HCP. |
| Bepirovirsen PFS SSD self-administered post-training | EXPERIMENTAL | Participants will receive Bepirovirsen PFS SSD self- administered with training by HCP. |
| Bepirovirsen PFS SSD self-administered without training | EXPERIMENTAL | Participants will receive Bepirovirsen PFS SSD self- administered with no training by HCP. |
| Name | Type | Description |
|---|---|---|
| Bepirovirsen | DRUG | Bepirovirsen will be administered. |
| Placebo | OTHER | Matching placebo will be administered. |
Inclusion Criteria: * 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...
Bepirovirsen is an investigational RNA therapy being developed for the treatment of chronic hepatitis B and hepatitis B infection. It is designed as an antisense oligonucleotide, a class of therapy that targets viral RNA. It is not yet approved and remains in clinical development.
Bepirovirsen targets hepatitis B virus, or HBV. It is an antisense oligonucleotide, often abbreviated as ASO, which is a type of RNA therapy designed to act on viral RNA. By targeting HBV RNA, the drug aims to reduce viral activity associated with chronic hepatitis B infection.
Bepirovirsen is being developed by GSK plc, which trades under the ticker GSK. GSK is running the clinical development program for the drug across multiple trials in hepatitis B, including studies in patients with chronic hepatitis B and in participants with both HIV and chronic hepatitis B virus infection.
Bepirovirsen is in Phase 3 clinical development. It is an investigational therapy and has not been approved by the FDA. The overall program includes five trials in total, with three currently active and two completed, spanning Phase 1 and Phase 2 studies alongside the Phase 3 stage.
Bepirovirsen trials include NCT07168356, a Phase 1 study of blood levels in adults with severe or moderate kidney disease, and NCT06497504, a Phase 2 study in people living with HIV and chronic hepatitis B, known as B-Focus. Completed studies include NCT06422767, which assessed cardiac conduction, and NCT06058390, which evaluated subcutaneous bioavailability.
Across the bepirovirsen clinical program, total enrollment is 1,838 participants. The trials are randomized, double-blind, and placebo-controlled. Individual study sizes range from 32 participants in a Phase 1 kidney disease study to 160 participants in a completed Phase 1 bioavailability study, with a Phase 2 HIV and hepatitis B study enrolling 153.