PII-020 - SIMILAR BIOAVAILABILITY OF SUBCUTANEOUS BEPIROVIRSEN WHEN DELIVERED FROM A VIAL OR PREFILLED SYRINGE FITTED WITH A SAFETY SYRINGE DEVICE IN HEALTHY ADULT PARTICIPANTS

A. Youssef¹, P. Shah², M. Hu³, R. Kaur⁴, A. Roy⁵, R. Sharma⁵, W. Cross⁶, B. Spears⁷, S. Pak⁸, R. Elston⁹, M. Hezareh⁹, D. Theodore¹⁰, A. Nader¹; ¹Clinical Pharmacology, Modelling and Simulation, GSK, Collegeville, Pennsylvania, USA, ²Clinical Research, Hepatology, GSK,, Stevenage, Hertfordshire, UK, ³Research and Development, GSK,, Shanghai, China, ⁴Global Clinical Operations, GSK, Stevenage, Hertfordshire, United Kingdom, ⁵Stats and programing, GSK, Bangalore, Karnataka, India, ⁶Medicine Development & Industrialisation, GSK, Stevenage, Hertfordshire, United Kingdom, ⁷PPD, Austin, Texas, USA, ⁸PPD, Las Vegas, Nevada, USA, ⁹Clinical Research, Hepatology, GSK, Stevenage, Hertfordshire, United Kingdom, ¹⁰Clinical Research, Hepatology, GSK, Durham, North Carolina, USA.

Background: Bepirovirsen, an antisense oligonucleotide, is designed to inhibit the synthesis of hepatitis B virus (HBV) viral proteins by directly targeting RNAs via RNase H mediated degradation, resulting in the reduction of viral proteins. Bepirovirsen is currently being delivered as vials in Phase 3. This study assessed the relative bioavailability (RBA) of bepirovirsen after administration with pre-filled syringes fitted with a safety syringe device (PFS-SSD) relative to vials, as well as the RBA of PFS-SSD after healthcare provider (HCP) and self-administration.

Methods: Intense plasma pharmacokinetic (PK) samples were collected from healthy participants who received a single 300 mg dose of bepirovirsen subcutaneously. Participants were stratified by body weight categories and injection site and randomized into 4 groups (Gp): administration by HCP of vial (Gp 1) or PFS-SSD (Gp 2); and self-administered PFS-SSD with (Gp 3) or without training (Gp 4). Bepirovirsen Cmax and AUC(0–inf) were estimated by noncompartmental analysis. RBA was assessed on the PK parameters using a fixed-effects model with fixed effects for treatment groups (Gp 2 vs Gp 1) and (Gp 3 or Gp 4 vs Gp 2). Injection site and body weight were added as covariates into the model.

Results: Bepirovirsen exposure was bioequivalent when administered by a PFS-SSD compared to vial: the 90% confidence intervals (CI) for the geometric mean ratio (GMR) were within 0.80 to 1.25 for Cmax (GMR: 1.02 [90% CI: 0.91, 1.14]) and AUC(0–inf) (GMR: 1.05 [90% CI: 0.96, 1.15]). Bepirovirsen exposure was bioequivalent when the PFS-SSD was self-administered (with or without training) compared to administration by HCP. Lower exposure after thigh administration was observed (60–94%) vs abdomen. Bepirovirsen exposure decreased with increasing body weight.

Conclusion: The results support the transition from vials to PFS-SSD, with the option of self-administration. The difference in exposure due to injection site or body weight is not clinically relevant and does not require dose adjustment based on preliminary PK/PD modeling.

Funding: GSK (study 219239)