Progress of new hepatitis B drugs VIR-2218 combined with VIR-3434 can significantly reduce HBsAg levels in patients with chronic hepatitis B

Hepatitis B virus (HBV) infection is endemic worldwide, with chronic HBV infection affecting about 257 million people
worldwide.
Current antiviral treatment regimens for chronic hepatitis B (CHB) are mainly drug treatments represented by nucleoside (acid) analogues (NA) and interferon (IFN)-α, but current therapies rarely achieve functional cures
for patients.
Therefore, it is necessary to continue to develop new anti-HBV therapies
.

VIR-2218 is a small interfering ribonucleic acid (siRNA) therapeutic drug targeting the HBx region of the HBV genome, and VIR-3434 is a human monoclonal antibody
targeting the hepatitis B surface antigen (HBsAg) antigen ring.
At the 2022 AASLD Annual Meeting of the American Society for the Study of Liver Diseases (AASLD 2022), researchers reported preliminary findings
on the safety, tolerability, and antiviral activity of VIR-2218 in combination with VIR-3434 in subjects with virus-suppressed chronic HBV infection.

Safety, tolerability and antiviral activity of VIR-2218 in combination with VIR-3434 in the treatment of chronic HBV infection: preliminary results of the Phase 2 MARCH trial announced

(Summary Number: 18)

Research methods

This is an open-label, Phase 2 study of adult patients
with chronic HBV infection who received continuous nucleoside (t.
)reverse transcriptase inhibitor therapy for ≥ 2 months.
Cohort 2 and Cohort 3 included only subjects
with HBsAg<3000 IU/mL at screening.

Participants in Cohort 1 received VIR-2218 200 mg at days 1 and 4, 8, 12, 16, and 20 (6 times) and VIR-3434 75 mg/qw doses (5 times)
at weeks 16 to 20 。 Subjects in Cohort 2 and Cohort 3 received VIR-2218 200 mg (3 times) on Day 1 and Weeks 4 and 8, and VIR-3434 18 mg/qw (12 times) or VIR-3434 75 mg/qw (12 doses)
from Day 1 to Week 11, respectively.

Research results

A total of 40 participants were included, of which 17 were cohort 1, 4 cohort 2 and 19 cohort
3.
HBsAg levels were reduced by > 1.
5 log₁₀IU/mL
from baseline in all subjects.
The HBsAg levels of Cohort 1, Cohort 2, and Cohort 3 changed from baseline at ± ± standard deviation by -2.
9 0.
7, -2.
7 ± 0.
3, and -2.
8 ± 0.
6 log₁₀IU/mL, respectively (Figure 1).

All subjects treated with VIR-3434 had HBsAg levels < 20 IU/mL
at their lowest point.

Fig.
1 Average change in HBsAg level from baseline in each cohort (log₁₀IU/mL)

A total of 18 participants (45%) reported adverse events (AEs), all of which had a grade 1 or 2 severity except for one creatine kinase elevated grade 3 AE (considered unrelated to study drug
) in cohort 3.
No severe AEs or withdrawals due to AEs have been reported
.
Follow-up visits are ongoing
.

Conclusion of the study

Combination therapy with VIR-2218 and VIR-3434 is generally well tolerated, with most AEs being mild
.
All combination regimens achieved an average reduction of HBsAg levels of > 2.
5 log₁₀IU/mL
at their lowest point.
These data support the continued development
of the combination of VIR-2218 and VIR-3434 for the treatment of chronic HBV infection.

References:

1.
DENG Mingxia, QIU Yunqing.
New progress of anti-hepatitis B virus drugs[J].
Journal of Clinical Internal Medicine, 2020,37(08):553-556.

2.
 Gane E, Jucov A, Dobryanska M, et al.
Safety, tolerability, and antiviral activity of the siRNA VIR-2218 in combination with the investigational neutralizing monoclonal antibody VIR-3434 for the treatment of chronic hepatitis B virus infection: preliminary results from the phase 2 march trial.
AASLD 2022.
Abrasts 18.