Vir Biotech’s Investigational Antibody Therapy Shows Promise in 8-Patient Phase 1 HBV Trial

On January 26th, San Francisco-based Vir Biotechnology announced that its monoclonal antibody therapy, VIR-3434 registered impressive Phase 1 results in patients suffering from chronic hepatitis B virus (HBV). The drug reduced the levels of hepatitis B virus surface antigen (HBsAg), a marker of active infection in the blood, in six out of eight patients. Vir’s stock jumped 40% since the announcement.

Chronic hepatitis B virus (HBV) infection is a potentially life-threatening disease and a major worldwide health problem. Although it can be prevented by vaccination, in 2015, an estimated 257 million people were living with a chronic HBV infection, and almost 900,000 people died from complications. The most severe complications include liver failure, liver cancer, and cirrhosis.

Currently, there is no cure for the disease, and existing treatments include antiretrovirals, and interferon injections, which reduce viral levels, decrease the risk of liver damage, and prevent viral transmission. However, these medications do not eliminate the virus, and life-threatening conditions still occur. Therefore, there is an unmet need for new medications that can eradicate or fully control virus levels.

VIR-3434

VIR-3434 is a neutralizing-monoclonal antibody that prevents HBV from entering liver cells. It can block all 10 variants of the virus, and it has been shown to reduce the number of infectious viruses and subviral particles in the blood. Besides, it is modified to carry a proprietary XX2 “vaccinal mutation,” which induces T cell activation and contributes to viral clearance.

The efficacy of VIR-3434 was tested on a randomized, placebo-controlled Phase 1 clinical trial. Out of the eight chronic HBV patients in the study, six received the treatment, and two received placebo. The results showed that the six patients showed a reduction in HBV surface antigen.

“Extrapolating from our preclinical data, we expected it might require much higher doses of VIR-3434 to achieve this level of HBsAg knockdown. To have achieved it with a dose of 6 mg is unexpected,” said Phillip Pang, M.D., Ph.D., Chief Medical Officer of Vir. “Coupled with initial data that shows VIR-3434 was well tolerated at up to 3,000 mg in healthy volunteers, I am hopeful that we are seeing just the beginning of VIR-3434’s capabilities.”

Vir also announced plans to begin a Phase 2 trial of VIR-3434 in combination with their HBV-targeting siRNA therapy, VIR-2218. This will be in addition to another Phase 2 trial that Vir plans to initiate in collaboration with Gilead Sciences. The Phase 2 trial intends to investigate the efficacy of VIR-2218 in combination with Gilead’s TLR8-agonist, selgantolimod, and a commercially-sourced PD-1 antagonist.

Potential Rivals

Currently, there are at least two more companies in Phase 2 clinical trials using antibodies as a therapy for HBV. Shanghai Henlius Biotech began clinical trials in late 2019 with HLX10, a PD-1 monoclonal antibody. Ascletis Pharma also began Phase 2 trials in mid-2020 for ASC22, a PD-L1 monoclonal antibody. The idea behind both therapies is to improve T cell function to eradicate the virus.

Related Article: Envafolimab, the First Subcutaneously Administered PD-L1 Antibody for HBV Enters Phase IIb Study

References

1. https://investors.vir.bio/news-releases/news-release-details/initial-data-ongoing-phase-1-trial-vir-3434-chronic-hepatitis-b
2. https://www.prnewswire.com/news-releases/first-hbv-patient-dosed-in-phase-iia-clinical-trial-of-asc22-a-subcutaneously-administered-pd-l1-antibody-301112931.html
3. https://www.gilead.com/news-and-press/press-room/press-releases/2021/1/gilead-and-vir-biotechnology-establish-clinical-collaboration-to-explore-combination-strategies-for-functional-cure-for-chronic-hepatitis-b-virus

Author

Daniel Ojeda