Research supports continuation of VIR-2218 development for hepatitis B

VIR-2218, an investigational small interfering ribonucleic acid therapeutic, was well tolerated in patients for the treatment of chronic hepatitis B virus, according to research presented at the International Liver Congress.

“VIR-2218 is a new type of small interfering ribonucleic acid (siRNA) that’s been modified by a chemical process called enhanced stabilization chemistry. By doing so, it allows the target drug to be more specific for the viral proteins and prevent any off-target effects on the patient's proteins or any nonspecific protein binding,” Edward Gane, MD, University of Aukland, said. “The preclinical data would support this increased safety compared with older generations of siRNAs; this targets a single trigger in the viral genome and allows a single trigger to knock down all the viral proteins with a single siRNA.”

In a proof-of-concept study investigating the impact of VIR-2218 on antiviral activity, researchers dosed 24 non-cirrhotic, virologically suppressed patients with HBV with either placebo or VIR-2218 on day 1 and day 29. Patients with negative hepatitis B e-antigen (n = 18) received 20 mg, 50 mg, 100 mg or 200 mg doses and patients with positive HBeAg (n = 6) received 50 mg or 200 mg doses. Investigators further assessed safety, hepatitis B surface antigen levels and other viral markers 12-weeks after the second dose.

Study results yielded maximum mean HBsAG (log₁₀ IU/mL) declines of 1.03, 1.23, 1.5 and 1.65 in HBeAG-negative patients who received VIR-2218 20 mg, 50 mg, 100 mg and 200 mg, respectively, and declines of 1.16 and 1.57 in HBeAG-positive patients who received VIR-2218 50 mg and 200 mg, respectively. Researchers noted most patients achieved maximum HBsAG decline by 16-weeks.

“An important observation from the study was that the higher the dose given, the longer the knockdown effect on HBsAG. We saw sustained responses in people who had, even a year after the last dose of treatment, a reduction on HBsAG,” Gane concluded. “Going forward, when we're looking at a functional cure, we'll be giving repeated dosing and in combination with other novel therapies. These results showed VIR-2218 did get full target engagement and did knock down all the HBV biomarkers.”