Combined VIR-2218, VIR-3434 therapy reduces HBV surface antigen
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WASHINGTON — Preliminary results showed combined VIR-2218 and VIR-3434 therapy reduced hepatitis B surface antigen with mild adverse events among a small subset of patients with chronic HBV infection.
“This audience is well aware of the current standard of care and the long-term issues regarding cost, potential risk of breakthrough and toxicity,” Edward J. Gane, MD, FAASLD, professor of medicine and deputy director of the New Zealand Liver Unit at the University of Auckland, said at The Liver Meeting. “Hence, there is a present need for developing a finite treatment strategy which is able to achieve durable loss of surface antigen of HBV DNA and improve outcomes for our patients.”
According to Gane, VIR-2218 and VIR-3434 are two new agents currently under development: VIR-2218 is an investigational, small interfering ribonucleic acid that targets the HBx region of the HBV genome, and VIR-3434 is an investigational Fc-engineered human monoclonal antibody that targets the conserved antigenic loop of HBsAG.
Gane and colleagues evaluated the safety, tolerability and antiviral activity of the combined therapies in the open-label, phase 2 MARCH study. They included 40 virally suppressed patients with chronic HBV who were divided into three cohorts: 17 patients received six doses of VIR-2218 200 mg at day 1 and weeks 4, 8, 12, 16 and 20 with five weekly doses of VIR-3434 75 mg at weeks 16 through 20 (cohort 1), while patients in cohorts 2 (n = 4) and 3 (n = 19) received three doses of VIR-2218 200 mg at day 1 and weeks 4 and 8 with 12 weekly doses of VIR-3434 18 mg or 75 mg, respectively, from day 1 through week 11. Patients in cohorts 2 and 3 had HBsAG less than 3,000 IU/mL at screening.
According to preliminary results, all patients achieved HBsAG decreases greater than 1.5 log10 IU/mL from baseline. The mean HBsAG from baseline at nadir was –2.9 ±0.7 log10 IU/mL in patients in cohort 1, –2.7 ±0.3 log10 IU/mL in patients in cohort 2 and –2.8 ±0.6 log10 IU/mL in patients in cohort 3. All patients who received VIR-3434 achieved absolute HBsAG levels less than 20 IU/mL at nadir.
Although additional follow-up is ongoing, Gane noted 45% of patients reported non-serious adverse events with no discontinuations.
“This combination of VIR-2218 and VIR-3434 for up to 20 weeks appeared to be well tolerated and associated with only mild adverse events,” Gane concluded. “This combination achieved mean surface antigen reductions greater than 2.5 logs across all cohorts, and most patients were suppressed to a surface antigen level less than 10 IU.”
He added, “These patterns of response suggest that you’re getting additive surface antigen reduction from combining these two drugs with different modes of action.”
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Gane EJ, 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. Presented at: The Liver Meeting; Nov. 4-8, 2022; Washington (hybrid meeting).
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