Vir Biotechnology Initiates Phase 2 Clinical Trial of RNAi-Immunotherapy Combination for Functional Cure of Chronic Hepatitis B

On December 9, 2021, Vir Biotechnology announced that the first patient had been dosed in a Phase 2 clinical trial of the investigational RNAi therapy VIR-2218 in a novel combination treatment for patients with chronic hepatitis B virus (HBV) infection. Vir is collaborating with Gilead Sciences to evaluate VIR-2218 in combination with the investigational TLR-8 agonist selgantolimod and the approved anti-PD-1 antibody nivolumab for the treatment of both treatment-naïve and treatment-experienced HBV patients, with the aim of achieving functional cure. Treatment-experienced patients may also receive treatment with the approved drug tenofovir alafenamide fumarate (TAF).

VIR-2218 is a subcutaneously administered siRNA targeting the X gene of HBV, jointly developed by Vir and Alnylam Pharmaceuticals. This targeting site allows it to inhibit the expression of hepatitis B surface antigen from both integrated viral DNA (intDNA) and covalently closed circular DNA (cccDNA) using a single siRNA, thereby stimulating an effective immune response and generating significant anti-HBV activity.

▲Introduction to VIR-2218 (Image Source: Reference [2])

This multicenter, open-label Phase 2 clinical trial aims to evaluate the safety, tolerability, and efficacy of various treatment combinations of VIR-2218 in conjunction with selgantolimod, nivolumab, and TAF for adult patients with chronic HBV infection. The trial will enroll approximately 120 patients aged 18-65 who have detectable hepatitis B virus in their blood or whose virus is suppressed after receiving approved HBV reverse transcriptase inhibitors, including patients positive for hepatitis B e-antigen (HBeAg, an indicator of active viral replication) and those negative for HBeAg. The primary endpoint of the trial is the proportion of patients achieving functional cure (defined as the disappearance of hepatitis B surface antigen in serum and HBV DNA <20 IU/mL at 24 weeks of follow-up).

References:

[1] Vir Biotechnology Announces Initiation of Phase 2 Clinical Trial Evaluating VIR-2218, Selgantolimod and Nivolumab for the Treatment of Chronic Hepatitis B Virus Infection. December 9, 2021, from https://www.globenewswire.com/news-release/2021/12/09/2349250/0/en/Vir-Biotechnology-Announces-Initiation-of-Phase-2-Clinical-Trial-Evaluating-VIR-2218-Selgantolimod-and-Nivolumab-for-the-Treatment-of-Chronic-Hepatitis-B-Virus-Infection.html

[2] Safety and Antiviral Activity of VIR-2218, An X-Targeting RNAi Therapeutic, In Participants With Chronic Hepatitis B Infection: Week 48 Follow-Up Results. Retrieved June 25, 2021, from https://investors.vir.bio/static-files/435251ac-661c-46a0-90a6-c5dd163235b2

(Original text has been abridged)

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