Vir Biotechnology begins patient dosing in phase 2 MARCH study of combination of VIR-2218 & VIR-3434 as functional cure regimen for chronic HBV infection
Vir Biotechnology announced that the first patient has been dosed in the phase 2 MARCH (Monoclonal Antibody siRNA Combination against Hepatitis B) trial evaluating VIR-2218 together with VIR-3434 for the treatment of patients with chronic hepatitis B virus (HBV) infection – a combination designed to achieve a functional cure.
VIR-2218 is an investigational small interfering ribonucleic acid (siRNA) designed to inhibit the production of all HBV proteins (X, polymerase, S and core), which may be acting as immune tolerogens. VIR-3434 is an investigational HBV-neutralizing monoclonal antibody designed to block entry of all 10 genotypes of HBV into hepatocytes, as well as reduce the level of virions and subviral particles in the blood. It has also been Fc engineered to include the XX2 “vaccinal mutation,” allowing it to potentially function as a therapeutic T cell vaccine against HBV.
“HBV infection remains an urgent global public health challenge associated with significant morbidity and mortality, and we believe that a combination approach focused on immune restoration will be critical to achieving a functional cure,” said Phil Pang, M.D., Ph.D., Vir’s chief medical officer. “We are excited about the potential of VIR-2218 to serve as the cornerstone of that approach. We believe that combining it with VIR-3434, which has already demonstrated the ability to markedly lower hepatitis B surface antigen at low doses in an ongoing Phase 1 trial, and, most importantly, has the potential to function as a therapeutic T cell vaccine, could be a game changer.”
The multi-center, open-label phase 2 trial is designed to evaluate the safety, tolerability and efficacy of the combination of VIR-2218 and VIR-3434 in approximately 90 adult patients (ages 18 to 65) with chronic HBV infection receiving nucleot(s)ide reverse transcriptase inhibitor therapy. Both VIR-2218 and VIR-3434 will be administered via subcutaneous injection at varying dose levels over the course of the trial for a treatment period ranging from four to 20 weeks, and a follow-up period of up to 116 weeks, depending on the dosing cohort. The primary endpoints of the trial are the proportion of patients with treatment-emergent adverse events and serious adverse events; grading of post-treatment clinical laboratory parameters; and the proportion of patients achieving a functional cure (defined as undetectable HBsAg and sustained suppression of HBV DNA).
VIR-2218 is an investigational subcutaneously administered HBV-targeting siRNA that has the potential to stimulate an effective immune response and have direct antiviral activity against HBV. It is the first siRNA in the clinic to include Enhanced Stabilization Chemistry Plus (ESC+) technology to enhance stability and minimize off-target activity, which potentially can result in an increased therapeutic index. VIR-2218 is the first asset in the company’s collaboration with Alnylam Pharmaceuticals, Inc. to enter clinical trials.
VIR-3434 is an investigational subcutaneously administered HBV-neutralizing monoclonal antibody designed to block entry of all 10 genotypes of HBV into hepatocytes and reduce the level of virions and subviral particles in the blood. VIR-3434, which has been Fc engineered to potentially function as a T cell vaccine against HBV in infected patients, also incorporates Xencor’s Xtend in order to have an extended half-life.
