Antiviral activity of VIR-2218 boosted by immunomodulators in treatment of chronic HBV
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WASHINGTON — Pegylated interferon alpha potentiated the antiviral activity of VIR-2218 in a small subset of noncirrhotic patients with chronic hepatitis B, according to preliminary data presented at The Liver Meeting.
“VIR-2218 is a GalNAc-conjugated siRNA shown to reduce hepatitis B surface antigen in patients with chronic hepatitis B infection, and pegylated interferon is an approved HBV treatment with low incidence of hepatitis B surface antigen seroclearance,” Man-Fung Yuen, MD, PhD, DSc, chair and chief of gastroenterology and hepatology at the University of Hong Kong, said. “We hypothesized that lowering the surface antigen with VIR-2218 in the context of immune stimulation by pegylated interferon may lead to surface antigen seroclearance in a greater proportion of our patients.”
In an open label, phase 2 study, Yuen and colleagues evaluated the safety and efficacy of VIR-2218 monotherapy or in combination with pegylated interferon alpha-2 alpha (PEG-IFN) among 79 noncirrhotic, virally suppressed patients with chronic HBV.
Participants were divided into five cohorts and received subcutaneous VIR-2218 200 mg every 4 weeks with or without subcutaneous PEG-IFN 180 µg weekly: six doses of VIR-2218 (n = 15, cohort 1), six doses of VIR-2218 plus 12 doses of PEG-IFN starting at week 12 (n = 15, cohort 2), six doses of VIR-2218 plus 24 doses of PEG-IFN (n = 18, cohort 3), six doses of VIR-2218 plus no more than 48 doses of PEG-IFN (n =18, cohort 4) or no more than 13 doses of VIR-2218 plus no more than 44 doses of PEG-IFN (n = 13, cohort 5). Cohorts 3 through 5 initiated VIR-2218 and PEG-IFN at the same time.
According to Yuen, 58 patients have completed 4 weeks of treatment and three patients have discontinued participation. Patients in cohorts 3, 4 and 5 who concurrently initiated therapy achieved greater declines from baseline hepatitis B surface antigen levels at week 24 (–2.4 ± 0.7 log10 IU/mL, –2.3 ± 0.9 log10 IU/mL and –2.1 ± 0.6 log10 IU/mL, respectively) compared with patients in cohort 1 who received only VIR-2218 (–1.9 ± 0.2 log10 IU/mL).
Yuen noted that four patients who received VIR-2218 with PEG-IFN had confirmed hepatitis B surface antigen loss and anti-HBs seroconversion, while two patients are pending subsequent measure. Most participants in cohorts 2 and 3 had more rapid post-treatment increases in HBsAg compared with patients in cohort 1.
“VIR-2218 alone or in combination with pegylated interferon was generally well-tolerated. Ten participants across all cohorts who received the combination of VIR-2218 and pegylated interferon achieved surface antigen seroclearance by week 48,” Yuen noted. “With the 31% loss of surface antigen, this study suggests that the antiviral efficacy of VIR-2218 can be potentiated by immunomodulators.”
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Yuen M, et al. Abstract 19. Preliminary 48-week safety and efficacy data of VIR-2218 alone and in combination with pegylated interferon alfa in participants with chronic HBV infection. Presented at: The Liver Meeting; Nov. 4-8, 2022; Washington (hybrid meeting).
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