Viral Hepatitis HBV/HBV Cure: GSK and VIR continue to invest in HBV Cure with expanded clinical development programs

GSK initiated a new Ph1 device study for bepirovirsen, and VIR expanded its Ph2 MARCH study with 2 additional experimental arms and increasing planned enrollment from 260 to 415.

Key Details and Assessment :

GSK Ph1 Bepi Device Trial

• A new Ph1 study (N=200 healthy volunteers) will compare bioavailability of bepirovirsen (ASO) when administered via subcutaneous (SC) injection from a vial (current formulation) or a prefilled syringe fitted with a safety syringe device (PFS SSD)
  • Positive data from this study would support development of a more convenient formulation for bepi, which could be self-administered by patients (current assumption is once weekly SC administration)
  • The investment to develop a PFS SSD for bepirovirsen reiterates GSK’s confidence in the ASO; results from this study are expected mid-2024

VIR Ph2 MARCH Trial

• VIR’s Ph2 MARCH trial is evaluating VIR-3434 (mAb) ± VIR-2218 (siRNA) ± Peg-IFNα for up to 48 weeks in patients with HBV
• Several changes were made to the Ph2 MARCH trial on ct.gov, including:
  • Enrollment was increased from 260 to 415
  • Two new study arms were added to test multiple doses of VIR-2218 + Peg-IFNα and VIR-3434 + Peg-IFNα (increasing from 12 to 14 arms/interventions)
  • Three new secondary outcome measures were added (see additional details below)
• Despite these changes to the Ph2 MARCH trial, the primary completion date for this study remains June 2027
• Addition of the two study arms with PegIFNα suggests that interferon may be a key component in VIR’s strategy to achieve functional cure in HBV
  • VIR presented modest off-treatment results at EASL 2023 where 16.1% (5/31) of patients who received who received VIR-2218 (siRNA) and PEG-IFNα achieved a sustained virologic response at 24-wks after end of treatment
  • The inclusion of the new study arms suggests that VIR is now attempting to understand optimized dose levels of the siRNA to improve the efficacy of the combination and potentially advise Ph3 study design
• As mentioned at VIR’s Q2 2023 earnings call, 24-wk on-treatment data of Ph2 MARCH trial (VIR-3434 (mAb) ± VIR-2218 (siRNA) ± Peg-IFNα) is expected at AASLD 2023
  • This data will provide some understanding of the combination’s therapeutic potential, however off-treatment data will need to be seen to assess the combination’s ability to achieve functional cure 
  • Assuming positive data and continued development, an approval as early 2030 is possible