Virion Therapeutics has reported breakthrough clinical data for VRON-0200, its first-in-class checkpoint modifier immunotherapy, showing unprecedented rapid declines in hepatitis B surface antigen (HBsAg) when combined with investigational antivirals in chronic hepatitis B patients. The Phase 1b results, presented at EASL 2025, demonstrate the potential for a paradigm shift in hepatitis B functional cure approaches.
Rapid and Profound Antiviral Response
In the combination therapy cohort, all evaluable patients (n=6) experienced rapid and profound HBsAg declines within 7 days of receiving their first combination dose, with reductions ranging from -3.6 to -1.3 log10IU/mL. These responses continued to decline with additional monthly dosing through Week 20, reaching ranges of -3.8 to -2.2 log10IU/mL.
Remarkably, two patients achieved complete HBsAg loss - one within just 7 days of the first combination dose and another at Day 140. All patients achieved HBsAg levels below 10 IU/mL by Day 35 and seroconverted from HBsAb negative to positive.
"These types of responses have not been previously reported, even with PEG-IFN containing regimens," noted Professor Ed Gane from the University of Auckland, one of the study investigators.
"Spark and Fan" Treatment Strategy
The clinical approach employs what Virion calls a "Spark and Fan" treatment model. VRON-0200 first "sparks" a new HBV-specific immune response through checkpoint modification, then the response is "fanned" by adding antivirals that remove the virus and its immunosuppressive effects.
"This novel and exciting approach, where a patient's immune response is 'sparked' with VRON-0200, and then 'fanned' by the removal of the HBV virus, and its immunosuppressive effects, with antiviral agents, may represent a paradigm shift in treatment approaches," Professor Gane commented.
Comprehensive Safety Profile
The Phase 1b trial enrolled 34 chronic hepatitis B patients across three cohorts, generating over 8,295 safety days for VRON-0200 monotherapy and 821 safety days for combination therapy. VRON-0200 demonstrated excellent tolerability with no serious treatment-related adverse events, treatment discontinuations, or treatment-related clinical laboratory abnormalities reported.
In patients receiving VRON-0200 alone (n=27), HBsAg declines were observed in 27% of patients through Day 154, ranging from -2.3 to -0.4 log10 IU/mL, despite VRON-0200 not directly targeting S-antigen. This suggests possible broadening and restoration of anti-HBV immune responses.
Clinical Trial Design and Patient Population
The Phase 1b study included non-cirrhotic, HBeAg positive or negative chronic hepatitis B patients currently on nucleos(t)ide antiviral therapy with HBV DNA < 40 IU/mL. The combination cohort (Cohort 3) received a single intramuscular VRON-0200 prime injection followed by monthly doses of elebsiran (a small interfering RNA) plus tobevibart (a monoclonal antibody against HBsAg) starting on day 28.
Addressing Global Health Burden
Chronic hepatitis B affects an estimated 254 million people worldwide and contributes to 1.1 million deaths annually from liver-related complications. Despite the availability of a preventative vaccine, cases continue to rise, representing a significant global health challenge with high unmet medical need.
"On this World Hepatitis Day, we are aware of the burden of CHB, and the urgent unmet medical need to achieve a functional cure that is safe, convenient, effective, and accessible for persons worldwide," said Dr. Sue Currie, Virion's COO.
Future Development Plans
Virion is developing a global Phase 2b study called "SPARK-B" for HBV functional cure, with additional manufacturing activities underway to support late-stage development. The company is also engaged in partnership discussions to accelerate development and maximize global access to a potential functional cure.
Longer-term clinical data from the full Phase 1b cohort is expected in Q4 2025, which will further inform future treatment strategies to maximize functional cure rates and potentially expand patient populations.
Professor Grace Wong from the Chinese University of Hong Kong, another study investigator, emphasized the clinical significance: "Treatment options for patients with Chronic HBV are very limited and often require up to a year, or sometimes longer, of treatment, with high rates of adverse events, and low rates of functional cure. These data demonstrate the potential to have a simple, well tolerated immune-modulator, that could be combined with other agents to potentially shorten the time of treatment and also improve the overall response rates."
